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664 Cards in this Set
- Front
- Back
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Clinical Oncology and Incidence of Cancer |
-No good registries or information on the true prevalence of cancer in companion animals --26% of deaths overall --46% of deaths in dogs over 10 years old -"Most common cause of death" in companion animals -80% of cancers have contributing environmental causes -Certain cancers have genetic predisposition -Pets may act as sentinels for environmental carcinogens |
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Cancer in Companion Animals |
-Associated with older animals -Cancer incidence may be increasing --Increased awareness --Increased diagnosis --Increased reporting |
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Factors allowing for increased cancer incidence in companion animals |
-Better vaccines -Better nutrition -Strict leash laws -Owner education and management -Increased environmental pollution
-Better at treating other diseases, animals live longer and are more disposed to cancer -Increased awareness leads to increased diagnosis and increased reporting |
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Causes for Cancer |
-Pollution: herbicides, pesticides, heavy metals -Occupational hazards: dust, vinyl chloride, asbestos -Habits: smoking, alcohol -Diet: high fat, low fiber, red meat -Infections: viral and parasites -Hormones -Physiological influences -Genetic predisposition or inherited genetic defects, mutations in tumor suppressor genes |
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Tumors and the Cell Cycle |
-Tumor cells as cells with unregulated growth -Do not stop/rest in G0 phase, continue to divide -Aggressive cancers have increased growth --continually go through cell cycle -Only actively dividing cells are affected by chemotherapy -Cancer drugs can be specific to certain phases of the cell cycle or can be "cell cycle non-specific" |
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4 Phases of the Cell Cycle |
-G1: protein synthesis, preparation for DNA replication -S: DNA synthesis and replication -G2: Preparation for cell division -M: Mitosis, cell division -G0: resting or quiescent phase after mitosis --cell may be recruited from G0 into actively dividing cycle |
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Chemotherapy and the Cell cycle |
-Tumors with high growth fraction are more sensitive to chemotherapy, easier to kill -Cells in specific phase of the cell cycle varies according to tumor histology, size, and stage of disease |
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Normal Tissue classification and Cell cycle activity |
-Renewing tissue: continuously proliferating population --stem cell population, clonal cells that can regenerate -Expanding tissue: has a sub-population of cells in G0, can be recruited to start dividing -Terminally differentiated tissue: static tissue --limited self-renewal --nerves, muscles, blood vessels, bone |
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Growth Fraction in Tumors |
-Not static -Starts high in young/new tumors -Slows down in older tumors, growth is not as fast |
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Regulation Of Cellular Growth |
-Normal tissue: number of cells produced is the same number of cells that die --balanced regeneration -Tumors: number of cells produced is greater than the number of cells that die --increased cell division and decreased cell death --more cells are produced than the number that die |
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Regulation of the Cell Cycle |
-Cell cycle needs to be strictly regulated -Regulation via checkpoints that repair damaged cells or stop the cell cycle -Step-wise progression through G1, S, G2, and M phases --regulated by interdependent CDKs and CDK inhibitors -G1 restriction point is major restriction point |
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G1 restriction point |
-Major restriction point, major point of growth regulation in the cell cycle -If cell progresses through checkpoint, cell becomes committed to division -Later checkpoints can edit or repair or arrest |
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Mechanisms of Increased Cell Division |
1. More cells produced -Proto-oncogenes result in increased cell divsion -cells are recruited from G0 -Growth fraction increases 2. Fewer cells die -Defective cells or loss of tumor suppressor genes -Decreased rate of cell death, decreased apoptosis 3. Cell cycle time shortens -cell cycle speeds up |
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Cell Cycle Deregulation |
-Oncogenes and tumor suppressor genes promote cell division and decrease apoptosis --Compromise cell cycle checkpoint functions -Progressive accumulation of genetic instability and mutations -Heterogeneous and ever-changing tumor cell population --several sub-populations of cells |
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Early Clinical Signs of Cancer |
-Abnormal swelling that persists or grows -Sores that do not heal -Unexplained weight loss -Loss of appetite -Bleeding or discharge from nose, mouth, rectum -Bad odor, foul breath -Difficulty eating or swallowing -Exercise intolerance or fatigue easily -Persistent lameness -Difficulty breathing, urinating, or defecating -Changes in Behavior |
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Diagnosing Cancer |
-Cytology: fine needle aspirate -Histopathology: tissue from tumor --gold standard for tumor diagnosis |
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Cytology for Cancer Diagnosis |
-Cells from tumor are evaluated for malignancy -Good screening tool -Can differentiate between inflammation and tumors -Can be diagnostic in some tumors --Lymphoma --Mast cell tumor |
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Histology for Cancer Diagnosis |
-Evaluates cells and growth patterns of cells -Gold standard for tumor diagnosis -Look at entire tissue and growth pattern -incisional: small part of tumor -Excisional: whole tumor -Provides information about tumor type and tissue of origin --information about biological behavior of tumor |
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Cancers that can be diagnosed with Cytology Only |
-Lymphoma: large blastic lymphocytes -Mast cell tumor: Big round cells with granules |
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Incisional Histopahtology for Cancer Diagnosis |
-Small section of the tumor is removed for evaluation -Trucut, wedge, or punch |
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Excisional Histopathology for Cancer Diagnosis |
-Whole tumor is removed with varying amount of normal tissue -Marginal -Wide -Radical (very wide excision) |
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Information from Histopathology for Cancer Diagnosis |
1. Tumor type or tissue type of origin (biological behavior) 2. Grade or differentiation of tumor (aggressiveness) 3. Completeness of surgical borders (margins) 4. Tissues can be used for special stains
Always send biopsy of ENTIRE tumor, not just a piece |
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Malignant Tumor Classification |
-Local invasion -Distant metastasis |
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Purpose of Staging Cancer |
-Evaluate general health of animal, whole patient helath -Identify and treat concurrent diseases -Gives idea for prognosis -Evaluate extent of the tumor -Guides treatment plan (avoid over-treatment or under-treatment) -Important for response evalulation -Influences owner's decision of whether to treat or not |
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How to stage Cancer |
-Biological behavior of the tumor -Primary tumor evaluation --histological type, grade, size, depth of local invasion --completeness of surgical excision -Presence of metastasis to local, regional, or distant sites |
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TNM system for staging tumors |
T: size and invasion of primary tumor --T0, T1, T2, T3 N: presence of lymph node metastasis --N0, N1, N2 M: Presence of metastasis --M0 and M1 |
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Staging the primary tumor |
-Size -Grade -Depth of invasion -Surgical margins |
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Staging of Regional or distant tumor spread |
-Lymph node biopsy -Laproscopy -Thoracoscopy -Histopathological confirmation of metastasis -more accurate than other staging modalities |
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Lymph Node Staging for Cancer |
-Carcinomas spread via lymphatics -Lymph nodes are first site of metastasis for many carcinomas -If lymph nodes are involved, high risk for distant metastasis --need systemic therapy -Biopsy before enlarged on physical exam -Doing a physical exam alone is not accurate in predicting lymph node status --Need cytology or histopathology --Histopathology is the gold standard, cytology is pretty sensitive and specific |
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Imaging used to stage Cancer |
-Radiography -Ultrasound -CT/MRI/PET -Nuclear Scintigraphy (Bone scan) |
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Radiology for Cancer Staging |
-Inexpensive option -Available in most hospitals or clinics -Main method used to image thorax -Need 3 views for cancer staging -Can detect pulmonary lesions more than 6mm in diameter -Cannot always get good resolution for which organ is involved |
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Ultrasound for Cancer Staging |
-Increasingly more available -Better than radiographs for evaluating parenchymal changes or abdominal organ involvement -Used to stage abdomen in patients with hematopoietic malignancies -Need to be careful when interpreting changes in ultrasound image as metastasis, could be a non-malignant change -Can be used to guide fine-needle aspirate for cytology, biopsies, or thoracocentesis -Generally used after radiographic images to evaluate consolidation, atlectasis, and masses |
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CT/MRI/PET for Cancer Staging |
-CT is standard for thoracic staging -MRI is standard for liver and brain lesions --gives limited information about tumor viability -PET detects changes in cells as they grow, identified rapidly growing celle --can detect cancer before anatomical changes are visible --can distinguish scar tissue from active tumors -Bone scans are used for skeletal cancers |
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Staging Cancer and Therapy |
-Predict risk of recurrence --determine need for adjunctive treatment -Predict site of recurrence -Determine type of treatment needed --surgery --radiation therapy --chemotherapy --multi-modal therapy -Establishes a baseline for measuring future changes -Important to gauge response |
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Cancer treatment Options |
-Surgery -Radiation therapy -Chemotherapy -Targeted therapy -Combination of modalities -Other modalities |
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Surgery as treatment for Cancer |
-Used for diagnosis via incisional or excisional biopsy -Most important and effective treatment for localized tumors -Often used in combination with other modalities -Can be palliative therapy in selected tumors |
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Radiation Therapy as treatment for Cancer |
-Used after surgery to treat localized or invasive tumors -Can be an alternative to surgery for select tumors --has cosmetic and functional advantage -Can be used with surgery to optimize control of a tumor --de-bulk a tumor, get rid of pieces remaining from surgery -Can be used in combination with other modalities also |
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Chemotherapy as Treatment for Cancer |
-Used to treat metastatic tumors -Can be used as adjunct to surgery or radiation if metastasis is a concern -Can be used before surgery to decrease the size of a tumor, sterilize borders, and decrease chance for metastasis -Can be used alone to treat multicentric cancers --lymphoma, leukemias -Palliative chemotherapy, decrease tumor burden and increase quality of life |
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Targeted Therapy for Cancer |
-Treatment is more specific to the type of cancer -Small molecules or monoclonal antibodies block growth and spread of cancer --interfere with specific pathway signaling molecules used by tumor for growth and progression -Palladia -Kinavet -Toxicities are common, may be due to lack of specificity |
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Palladia Kinavet |
-Small-molecule tyrosine kinase inhibitors -Used in targeted therapy for cancer -Mostly used in canine mast cell tumors |
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Anatomy of the Ovary |
-Close to the kidney, caudal pole of the kidney -Right ovary is more cranial than the left, more difficult to expose -Attached to abdominal wall by mesovarium -Medulla and cortex to the ovary -Ovarian vessles are contained in the mesovarium -Enclosed in ovarian bursa |
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Ovary Cortex |
-Outer layer -Follicles form here -Follicles are surrounded by granulosa cells (basement membrane) -Capsule: Tunica albuginea |
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Peritoneal reflections relating to the uterus and ovary |
-Mesovarium: Surrounds ovaries --filled with fat -Mesometrium: surrounds uterus |
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Ovarian Bursa |
-Peritoneal pouch -Encloses ovary -Slit that covers the ovary
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Visualizing the Ovary |
-Difficult due to fat (dog) --cat has no fat -Need to palpate the ovary -In dog ovary sits in ovarian bursa surrounded by fat -Need to remove ALL of the ovary! do not leave any tissue!
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Ovarian blood supply |
-Arterial: --ovarian artery, branch off the aorta --branches of the uterine artery -Venous: --right ovary drains into the caudal vena cava --left ovary drains into the renal vein |
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Anatomy of the uterus |
-Attached to body wall by mesometrium -Has 2 horns, a body, and a cervix -Uterine tube/oviduct connects ovary to the uterus |
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Uterine Blood Supply |
-Arterial: --uterine artery, branch of the internal pudendal artery -Venous: uterine vein, branch of the internal pudendal vein
Both run along the entire length of the uterus -May have a branch that comes off and goes to the ovary |
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Uterine Nerve Supply |
-Parasympathetic Innervation: pelvic nerves -Sympathetic Innervation: Aortic lumbar nerves -Lymphatic drainage: medial iliac and aortic lumbar lymph nodes |
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Ligaments of the Uterus |
-Broad ligament -Suspensory Ligament -Proper ligament -Round ligament |
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Broad Ligament |
-Divided into mesovarium, mesosalpinx, and mesometrium -Peritoneal reflection that holds the uterus to the body wall |
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Suspensory Ligament |
-Connects the ovary and cranial mesovarium to the last rib -Lateral to the kidney, can palpate the body wall -Needs to be broken down in order to remove the ovaries |
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Proper Ligament |
-Connects the caudal ovary to the crainal uterine horn -Continuation of the suspensory ligament -Allows for manipulation of the ovary and uterus together |
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Round Ligament |
-Firm structure within the broad ligament -Extension of the proper ligament -Goes through the broad ligament and the inguinal ring |
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Diagnosing Disorders of the Ovary |
-Abdominal Palpation: ovaries are not palpable unless enlarged --uterus is a tubular structure ventral to the colon, can be palpated during pregnancy -Radiographs: uterus is difficult to differentiate from intestines unless enlarged --Can see fetal skeletons due to ossification in the last 15 days of gestation -Ultrasound is the key diagnostic tool --can use during pregnancy after 30 days of gestation -Exploratory laparotomy and biopsy |
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Congenital Disorders of the ovary |
-Supernumary ovaries: "3rd ovary" separate from normal ovary -Accessory ovary: "3rd ovary" close/connected to the normal ovary -Agenesis: ovary fails to form --can be unilateral or bilateral --uterus may also be absent or hypoplastic |
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Acquired lesions of the Ovary |
-Ovarian Cysts --follicular --lutein --Paraovarian -Ovarian Tumors --sex cord- Stromal tumors --epithelial tumors --germ cell tumors |
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Follicular Cysts |
-Persistant graafian follicle -Produces estrogen -Can prolong estrus, cause mammary hyperplasia, aggressiveness, or aplastic anemia |
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Lutein Cysts |
-Form after ovulation, from Corpus Luteum that persists -Produces progesterone -Causes cystic endometrial hyperplasia, pyometra |
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Paraovarian Cysts |
-Mesonephric/Wolffian or paramesonephric duct remnants -No clinical signs |
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Sex cord Tumor |
-Granulosa-theca cell tumor is most common -May produce estrogen, progesterone, or both -More likely to metastasize in cats than in dogs |
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Epithelial tumors of the Ovary |
-Derived from mesothelium covering the ovary -Can be adenomas, adenocarcinomas -Most common type of ovarian tumors |
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Ovarian Adenocarcinoma |
-50% metastasize at the time of diagnosis, high chance for metastasis -Can cause carcinomatosis, grave prognosis -Blocks lymphatic drainage and can cause ascites --physical obstruction |
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Germ Cell Tumors |
-Teratoma -Dysgerminoma (early stage, does not differentiate) -Both are usually benign but can be malignant |
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teratoma |
-Differentiated germ cell tumor -Usually benign -Differentiates beyond primordia germ cell -Enlarged ovary with calcific densities |
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Treatment for Ovarian Lesions |
-Depends on tumor or cyst type and stage -Age and overall condition of animal are important to consider -Breeding potential can be a factor -Surgery is best treatment --ovariectomy vs. ovariohysterectomy --unilateral nephrectomy due to left ovarian vein draining into renal vein --May or may not do body wall excision |
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Prognosis for Ovarian Lesions |
-Depends on type of lesion -Good prognosis: --benign lesions without bone marrow suppression -Poor prognosis: --metastasis or bone marrow suppression |
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Congenital Anomalies of the uterus |
-Structural abnormalities (under-developed or absent) -Rare or incidental findings -Uterus unicornis (one horn) --one horn does NOT mean one ovary!! Check for 2 -Hypoplasia -Segmental aplasia -Agenesis (no uterus) -Septate uterine body |
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Acquired Uterine Disorders |
-Poymetra -Hydrometra/Mucometra -Neoplasia -Intussusception -Torsion -Prolapse -Rupture -Metritis -Subinvolution of placental sites |
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Pyometra |
-Pus filled uterus -Occurs during diestrus due to CL secreting progesterone -Develops only in a progesterone environment --cystic endometrial hyperplasia -History is important! Pyometra only occurs during diestrus -Repeated exposure to progesterone promotes endometrial gland secretions --inhibits myometrial contraction -Usually occurs in middle-aged animals, not young animals -Progesterone inhibits leukocyte activity and maintains a closed cervix --predisposes uterus to infection or inability to clear infection
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Pyometra and Estrogen |
-Estrogen enhances the effects of progesterone -Promotes bacterial colonization -Progesterone primes the uterus and gives proper environment for bacteria to cause infection --bacteria is not the primary initiator -Usually an E. coli infection |
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Pyometra Signalment |
-Intact female dog over 6 years old: --Years of hormonal activity, lots of exposure to progesterone -Intact female dogs less than 6 years old: --estrogen administration -Uncommon in cats |
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Pyometra in Cats |
-Uncommon -Cats are induced ovulators, have less exposure to progesterone over lifetime |
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Pyometra Presenting History |
-During diestrus -Dogs Present within 8 weeks of last estrus -Cats present within 4 weeks of estrus |
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Pyometra Clinical Signs |
-Depends on patency of the cervix and duration of illness --closed cervix: sick animal --open cervix: allows drainage, less sick animal -Anorexia, PU/PD, lethargy/depression, vaginal discharge, vomiting, diarrhea -Most have normal temp, 20-30% will have a fever |
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Pyometra Physical Examination |
-Vaginal discharge --pus-colored fluid, may have some blood -Uterine distension on abdominal palpation |
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Pyometra Clinical Pathology |
-Moderate to severe neutrophilia -Non-regenerative anemia -Azotemia -Hypoalbuminemia -Hyperglobulinemia -Increased alk phos |
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Pyometra Urinalysis |
-DO NOT DO A BLIND CYSTOCENTESIS!!! --do not want to accidentally rupture the uterus, could be friable or fragile and explode putting bacteria everywhere -Azotemia, often pre-renal (dehydration) --USG will be increased -May have concurrent UTI or cystitis -Decreased urine concentrating ability --E. coli endotoxin decreases effects of ADH on renal tubules
Pyometra and UTI tend to go together |
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Pyometra Radiographs |
-Homologous tubular structures in the caudal abdomen -Can see tubular structures on radiographs |
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Pyometra on Ultrasound |
-Can determine uterine size, thickness, and fluid presence |
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Pyometra Treatment |
-Initially stabilize the patient -Perform ovariohisterectomy, remove uterus and ovaries --IMMEDIATE surgery if cervix is closed --not as immediate if cervix is still open -Medically manage for clinically stable breeding animals --difficult, eventually will probably have to remove |
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Ovariohisterectomy for Pyometra |
-Same as normal OVH -basically just a spay! Same complications as normal spay -Chance of rupture is increased, need to be careful -If severely distended, can have hemorrhage or uterine rupture |
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Medical Therapy for Pyometra |
-Only do for healthy breeding animals with open cervix --OPEN CERVIX is critical!! -Recurrence is common, will get another pyometra -Often is not cheaper than a surgery -Goal is to lower progesterone levels, eliminate bacteria, and open the cervix -Animal needs to be hospitalized during the treatment
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Pyometra and Prostaglandin F2 |
-Animal needs to be clinically stable and cervix needs to be open -Causes generalized smooth muscle contraction -Empties the uterus -Side effects of Prostaglandin: nausea, vomiting, diarrhea -Animal needs to be treated in the hospital for multiple days -May not see effects for 48 hours -Antibiotics |
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Hydrometra/Mucometra |
-Basically a sterile pyometra --endometrial secretions are controlled by progesterone stimulation -Usually an incidental finding -Can cause mechanical obstructions |
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Uterine Neoplasia |
-Dogs: Leiomyoma, leiomyosarcoma --benign is more common -Cats: Adenocarcinoma, adenoma --malignant is more common -Treatment: remove the uterus |
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Uterine Intussusception |
-Extremely rare, only one reported case -Chronic vaginal discharge -Treatment: remove the ovaries and uterus |
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Uterine Torsion |
-Single horn twists on itself and causes necrosis --ischemia leads to necrosis -Presentation: acutely painful abdomen -True surgical emergency -have to remove the whole uterus |
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Uterine Prolapse |
-Uterus prolapses through the cervix -Can be one horn or the entire uterus -Usually happens during parturition or 48 hours post-partum -Treatment: spay --could reduce and tack uterus to body wall, but best choice is to remove completely |
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Metritis |
-Usually occurs immediately postpartum -Malodorous, mucopurulent discharge -Animal is often sick -Treatment: OVH --can medically treat with healthy animals --drain uterus and instill antibiotics via catheter |
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Sub-involution of placental sites |
-Disturbance in normal placental degeneration and endometrial reconstruction -Fetal trophoblast cells continue to invade the myometrium --normally fetal trophoblast cells should die and be resorbed -interferes with normal involution -Will see persistent serosanguineous discharge 7-12 weeks after parturition -Treatment: OVH --may spontaneously regress |
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OVH vs. OVE |
-Need to remove entire ovary! -No ovary, no progesterone, no risk of pyometra |
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Laproscopic OVH/OVE |
-Potentially lower pain and increased activity -Large learning curve, longer surgical time, expensive! |
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OVH complications: Abdominal Hemorrhage |
-Most common cause of mortality after OVH -Need to make adequate incision size -Ligate vessels individually -Ligate the broad ligament -Check pedicles!!! do not drop the pedicles! |
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OVH complications: Vaginal hemorrhage |
-Erosion of uterine vessels -Infection of vessels around uterine vessel ligatures -Occurs 4-16 days post OVH |
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OVH complications: Recurrent Estrus |
-Residual ovarian tissue -Dropped tissue -Improper clamp placement -Ectopic or accessory ovaries -Clinical signs look like estrus -May be difficult to confirm without surgery -Do not leave pieces of the ovary in the animals!! |
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OVH complications: Stump Pyometra |
-Infection of the uterine stump -Progesterone environment is still present, ovarian tissue must be present |
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OVH Complications: Ureter ligation or cutting |
-More likely to occur if there is a dropped pedicle or a distended bladder |
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Other OVH Complications |
-Fistula tracts: inflammatory response to suture material -Uterine Stump granuloma: inflammatory response to suture material -Urinary incontinence: adhesions, granulomas, urethral sphincter -Weight gain |
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RBC lifespan in a cow |
-160 days |
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Transfusion reactions in a cow
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-Rare, no cross-matching is needed |
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Amount of blood in a cow
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-56L
-Can lose 12-13L with no significant effects |
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Cow normal PCV and TS
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-PCV= 30-38%
-TS= 7.2 |
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Immature RBCs
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-Larger
-Chromatin particles (need stain to see) -Heterochromasia, different colors |
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Anisocytosis
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-RBCs of different sizes present
-On blood smear indicates regeneration, immature RBCs |
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Causes of Anemia in Cows |
1. Blood loss 2. Increased RBC destruction 3. Decreased RBC production
In cows, can figure out which one is happening based on PCV and TS |
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Cow Blood Loss Anemia |
-Decreased PCV and decreased TP |
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DDx for cow blood loss anemia
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-Trauma
-Internal parasites -External parasites -Abomasal ulcer and bleeding --common in 1st calf heifers |
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Tx for Cow blood loss anemia |
-Transfusion |
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Rare causes of blood loss in Cows
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-Clotting problem
-Thrombocytopenia: occurs with virulent BVD strain --may see in clusters -Clotting factor deficiency |
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Clinical signs of RBC destruction in Cows
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-Hemolysis
-Decreased PCV, normal TS, Icterus -Increased HR, increased lactate due to poor O2 carrying capacity -Icterus is a main finding |
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Extravascular Hemolysis in Cows
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-RBCs have membrane defect or surface Ab expression
-Splenic macrophages remove RBCs from circulation -Free Hb is not released into plasma, plasma is not pink (is yellow) -Common with Anaplasma -IMHA is very rare in cows, possible DDx but very rare |
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Anaplasma in Cows
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-Common cause of extravascular hemolysis in cows
-Transmitted by ticks or dirty needles |
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Intravascular Hemolysis in Cows
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-RBCs are lysed directly into vasculature
-Hb is released into plasma, plasma is pink -Hb is in urine, urine is red |
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DDx for Intravascular Hemolysis in Cows
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-Clostridial diseases:
--Black’s disease --Clostridium Haemolyticum -Drinking too much water too quickly --H2O is hypo-osmotic, is pulled into RBCs and causes RBC swelling and lysis --Osmotic hemolysis |
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DDx for Intravascular Hemolysis in Sheep
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-Copper toxicity
-Cupper causes oxidative damage to the RBCs -Will see Heinz bodies |
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Tx for Intravascular Hemolysis in Cows
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-Penicillin
-Diuresis for Kidney, otherwise Hb builds up and damages kidney |
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Decreased RBC production in Cows
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-Most often due to Anemia of Chronic Disease or Chronic Infection |
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Important points of Equine Hematology
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-Horses have massive splenic contraction (makes PCV a poor indicator of acute severe hemorrhage)
-Horses don’t have reticulocytes -Horse plasma is often Icteric -Horses with Endotoxemia are neutropenic (key feature of horses exposed to gram- bacteria) -Foals with sepsis or SIRS are often neutropenic -Horses with infection have neutrophilia |
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Unique features of the Equine RBC
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-Rouleaux formation
-Variable packed cell volume due to packing, stacking, and splenic contraction -Plasma is Icteric -No peripheral signs of regeneration, no reticulocytes -Howell-Jolly bodies present |
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Equine RBC appearance
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-6-7 micrometers
-Highly deformable --allows RBCs to fit into small capillaries better --Enhances O2 exchange -RBCs are “soft bags of Hb” |
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Equine RBC Rouleaux Formation
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-RBCs aggregate and cross-link |
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Spleen and Variable PCV
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-Spleen can store 33-60% of circulating RBCs
-Splenic contraction is under sympathetic control --contracts during exercise or stress -Maximum exercise PCV = 66% --racehorse: 55-65 --pony: 35-45 |
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Horse PCV
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-Not a reliable indicator
-May under-estimate acute blood loss -May over-estimate dehydration -Best to follow trends, repeat evaluation -Evaluate PCV changes in comparison to changes in total solids --acute hemorrhage: decrease in TS occurs before change in PCV |
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Equine Plasma
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-Naturally icteric, normally yellow
-increased beta-carotenes in grass diet? -higher bilirubin concentration? |
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Equine Reticulocytes
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-Reticulocytes are not released from the bone marrow
-Regenerative bone marrow response will not stimulate reticulocyte release -No immature RBCs in circulation -Need to do a bone marrow aspirate to determine RBC regeneration |
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Howell-Jolly Bodies
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-Basophilic nuclear remnants in cytoplasm of equine RBCs |
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Anemia
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-Decrease in circulating RBC mass |
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Categories of Anemia |
-Subacute hemorrhage
--takes days -Chronic hemorrhage -Hemolysis (increased RBC destruction) -Non-regenerative anemia (decreased RBC production) -Acute hemorrhage |
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Clinical signs of Anemia
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-Pale mm
-Tachycardia -Tachypnea -Decreased exercise levels, lethargy --collapse if severe -Depression, dull, reduced energy level |
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How to Diagnose Anemia
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-History
-Physical examination -CBC -Leukogram, plasma protein evaluation -Bone marrow aspirate and analysis -Urinalysis -Test serum iron and total iron binding capacity -Coggins test for EIA -Coombs test for Ab on RBC cell surface or in serum |
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Characterizing Anemia
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1. RBC size and Hb content
-Normocytic: normal size -Microcytic: small size -Macrocytic: large size -Normochromic: normal Hb content -Hypochromic: low Hb content 2. Bone marrow response |
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Indicators of Hemolysis
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-Hb-uria
-Hb-emia -Increase in MCV (size) |
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Non-regenerative Anemia
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-Inadequate bone marrow erythropoiesis
-Low serum iron -Low total iron-binding capacity |
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DDx for non-regenerative Anemia
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-Fe deficiency:
--chronic hemorrhage --Nutritional -Chronic disease --neoplasia --chronic infection -Bone marrow Failure --myelophthisis --bone marrow toxicity -Iatrogenic (EPO administration) |
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Anemia Treatment
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-Whole blood transfusion
-Treat underlying disease -Oxyglobin -Colloid fluid support -Fe deficiency is a rare cause of anemia in the horse, usually do not give Fe supplement |
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Equine Transfusion Volume
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(Desired PCV – Patient PCV)*(0.08*Body weight kg)/PCV of donor
0.08 = blood volume per body mass --low in horses, higher in small animals |
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Signs of Hemorrhage in horses
|
-Challenge is to detect the “anemia”
-Initially there is no change in PCV or other hemostatic parameters -May see tachycardia, tachypnea |
|
|
Areas for Acute blood loss in Horses |
-Splenic |
|
|
Acute Blood Loss in Equine Neonates |
-Rib fracture and cardiac or large vessel laceration
-Orthopedic injury and large vessel injury |
|
|
Treatment of Acute Blood Loss in Horses |
-Transfuse or not transfuse:
--look at patient, not just one parameter --RBC indices, physiologic indicators, O2 delivery |
|
|
Spleen and Variable PCV
|
-Spleen can store 33-60% of circulating RBCs |
|
|
Horse PCV
|
-Not a reliable indicator
-May under-estimate acute blood loss -May over-estimate dehydration -Best to follow trends, repeat evaluation -Evaluate PCV changes in comparison to changes in total solids --acute hemorrhage: decrease in TS occurs before change in PCV |
|
|
Equine Plasma
|
-Naturally icteric, normally yellow
-increased beta-carotenes in grass diet? -higher bilirubin concentration? |
|
|
Equine Reticulocytes
|
-Reticulocytes are not released from the bone marrow
-Regenerative bone marrow response will not stimulate reticulocyte release -No immature RBCs in circulation -Need to do a bone marrow aspirate to determine RBC regeneration |
|
|
Howell-Jolly Bodies
|
-Basophilic nuclear remnants in cytoplasm of equine RBCs
-Not clinically significant -NOT Heinz bodies, do not indicate oxidative damage --more in the center of the RBC, Heinz bodies are on the cell membrane --need to do methylene blue stain to see Heinz bodies |
|
|
Anemia
|
-Decrease in circulating RBC mass
-Clinical sign, hematologic abnormality -NOT a diagnosis -Causes decreased O2 carrying capacity -Look at PCV, RBC count, Hb, splenic effect |
|
|
Categories of Anemia
|
-Subacute hemorrhage
--takes days -Chronic hemorrhage -Hemolysis (increased RBC destruction) -Non-regenerative anemia (decreased RBC production) -Acute hemorrhage |
|
|
Clinical signs of Anemia
|
-Pale mm
-Tachycardia -Tachypnea -Decreased exercise levels, lethargy --collapse if severe -Depression, dull, reduced energy level |
|
|
How to Diagnose Anemia
|
-History
-Physical examination -CBC -Leukogram, plasma protein evaluation -Bone marrow aspirate and analysis -Urinalysis -Test serum iron and total iron binding capacity -Coggins test for EIA -Coombs test for Ab on RBC cell surface or in serum |
|
|
Characterizing Anemia
|
1. RBC size and Hb content
-Normocytic: normal size -Microcytic: small size -Macrocytic: large size -Normochromic: normal Hb content -Hypochromic: low Hb content 2. Bone marrow response |
|
|
Indicators of Hemolysis
|
-Hb-uria
-Hb-emia -Increase in MCV (size) |
|
|
Non-regenerative Anemia
|
-Inadequate bone marrow erythropoiesis
-Low serum iron -Low total iron-binding capacity |
|
|
DDx for non-regenerative Anemia
|
-Fe deficiency:
--chronic hemorrhage --Nutritional -Chronic disease --neoplasia --chronic infection -Bone marrow Failure --myelophthisis --bone marrow toxicity -Iatrogenic (EPO administration) |
|
|
Anemia Treatment
|
-Whole blood transfusion
-Treat underlying disease -Oxyglobin -Colloid fluid support -Fe deficiency is a rare cause of anemia in the horse, usually do not give Fe supplement |
|
|
Equine Transfusion Volume
|
(Desired PCV – Patient PCV)*(0.08*Body weight kg)/PCV of donor
0.08 = blood volume per body mass --low in horses, higher in small animals |
|
|
Signs of Hemorrhage in horses
|
-Challenge is to detect the “anemia”
-Initially there is no change in PCV or other hemostatic parameters -May see tachycardia, tachypnea |
|
|
Areas for Acute blood loss in Horses
|
-Splenic
-Uterine -Post-cstration -GI -Guttural pouch -Trauma to large vessels -Neoplasia |
|
|
Acute Blood Loss in Equine Neonates
|
-Rib fracture and cardiac or large vessel laceration
-Orthopedic injury and large vessel injury |
|
|
Treatment of Acute Blood Loss in Horses
|
-Transfuse or not transfuse: |
|
|
Causes for Sub-acute or chronic blood loss in Horses
|
-Ulcerative blood loss |
|
|
Immune-mediated Hemolysis in the horse
|
-Hemolytic Anemia |
|
|
Infectious Hemolysis in Horses
|
-EIA
|
|
|
Oxidative Hemolysis in Horses
|
-Red Maple Leaf Toxicity
-Phenothiazine |
|
|
Clinical relevance of the Leukogram in Horses
|
-Primary diseases of WBCs is very rare
-Interpretation helps in developing a problem list -Helps refine possible Differential Diagnoses |
|
|
Equine Neutrophil margination
|
-Indicates endotoxemia!
-Will have neutropenia on CBC |
|
|
Physiologic Leukocytosis in Horses
|
-Lots of circulating Lymphocytes, mostly T-cells
-Epinephrine release causes transient increase in WBCs --occurs with excitement or exercise --exercise will increase eutrophils and lymphocytes |
|
|
Neutrophilia in Horses
|
-Bacterial infection or inflammation
-Regenerative left shift -Rebound neutrophilia after period of neutropenia -Chronic conditions cause little change in neutrophil count -Administration of corticosteroids -Toxic changes in WBCs without increase can be clinically relevant |
|
|
Neutropenia in Horses
|
-Indicates Endotoxemia
-Associated with GI disease -Neutrophils are marginating -bacterial septicemia in the neonate -Degenerative left shift, immature band cells appear in peripheral blood |
|
|
Rare causes of neutropenia in horses
|
-Bone marrow suppression by drugs
-Myelopthisic disease -Idiopathic aplastic anemia -Myelofibrosis |
|
|
Lymphocytosis in Horses
|
-Pathologic lymphocytosis is uncommon in horses
--May be due to lymphosarcoma, viral infections, or autoimmune disease -Lymphocytic leukemia is rare -Physiologic lymphocytisis occurs with epinephrine release in horses under 2 years old --stress or excitement in young horses |
|
|
Lymphopenia in Horses
|
-Profound lymphopenia can be due to acute viral disease, endotoxemia, severe bacterial infections, septicemia, immunodeficiency
-Rickettsial diseases -Malnutrition -Corticosteroids -Tumors that result in corticosteroid release -Persistent lymphopenia is a poor prognostic indicator |
|
|
Monocytes in Horses
|
-Monocytosis: Chronic inflammation
--not useful part of leukogram -Monocytopenia: endotoxin release and viremia --occurs during periods of stress associated with corticosteroid release |
|
|
Eosinophils in Horses
|
-Eosinophilia: uncommon
--occurs with diseases that involve interaction of antigen, IgE, and mast cells or basophils --Parasitic infection, allergic respiratory diseases, dermatoses -Eosinopenia is difficult to evaluate |
|
|
Basophils in horses
|
-Rarely seen in peripheral blood
-Difficult to interpret basophilia or basopenia -Basophilia can be due to allergic dermatitis, delayed hypersensitivity reactions |
|
|
Red maple Toxicosis in horses
|
-Toxin is in dried leaves
-Causes methemoglobinemia, Heinz body anemia -Clinical presentation: --anemia --pigmenturia --chocolate or dark muddy mm --acute death, abortion, pulmonary thrombosis |
|
|
Red Maple Toxicosis treatment
|
-Ascorbic acid/Vitamin C
-Fluid Therapy -Blood Transfusion |
|
|
Main points for Equine Hematology
|
-Horses have massive splenic contraction
--makes PCV a poor indicator of acute severe hemorrhage -Horses do not have reticulocytes -Horse plasma is often icteric -Horses with endotoxemia are neutropenic -Foals with Sepsis or SIRS are neutropenic -Horses with infections have neutrophilia |
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|
Chemotherapeutic Therapy |
-Has an effect on ALL dividing cells, not just malignant cancer cells
-Higher growth fraction in malignant cancer cells allows for increased sensitivity to chemotherapy -Narrow therapeutic index --maximal anti-cancer effect has mild to moderate toxicity associated -Steep dose-response curve --small decrease in dose results in major decrease in response -Cell cycle activity determines response to chemotherapy |
|
|
Small tumors and chemotherapy
|
-Small tumors:
--most cells are actively cycling, high growth fraction --steep growth curve --Short doubling time --kinetically favorable to chemotherapy |
|
|
Large tumors and chemotherapy
|
-Large tumors:
--few cells are actively dividing --Large fraction of cells in G0, low growth fraction --Long doubling time --Growth curve is flattening out --Kinetic resistance to chemotherapy |
|
|
Lymphoma and Chemotherapy
|
-Growth fraction stays high throughout tumor growth
-Maintains high susceptibility/sensitivity to drugs -Solid tumors, growth fraction decreases as tumor grows --results in kinetic resistance to drugs |
|
|
Classes of Chemotherapeutic Drugs
|
-Tumor Antibodies
-Alkylating Agents -Vinca Alkaloids -Antimetabolites -Miscellaneous drugs |
|
|
Anti-tumor Antibiotics
Anthracyclines |
-Doxorubicin (Adriamycin)
-Cell cycle non-specific, works against all phases of the cell cycle --wide opportunity to kill tumor cells -DNA intercalation -Enhances topoisomerase II activity, causes DNA fragmentation or breaks -Enhances free radicals -Hepatic excretion |
|
|
Doxorubicin Activity and Indications
|
-Broad-spectrum anti-cancer activity
-Effective against lymphomas, leukemias, carcinomas, sarcomas -Most important player in lymphoma cancer treatment |
|
|
Doxorubicin Toxicity
|
-Acute: Bone marrow effects and enterocolitis
-Chronic: dilated cardiomyopathy in dogs, renal failure in cats --irreversible changes, permanent and often progressive |
|
|
Drugs related to Doxorubicin
|
-Epirubicin
-Idarubicin -Daunorubicin -Mitoxantrone |
|
|
Cyclophosphamide
|
-Alkylating Agent
-Cell cycle non-specific -Alkylates DNA, produces inter and intra-strand cross-links -Interferes with DNA replication and RNA transcription -Metabolism needs multi-step activation in peripheral tissues, liver, and kidneys |
|
|
Cyclophosphamide Indication
|
-Combination protocols, usually an add-on drug
-Lymphoma -Leukemia -Sarcoma -Carcinomas |
|
|
Cyclophosphamide Toxicity
|
-Bone marrow
-GI -Sterile hemorrhagic cystitis -Secondary malignancies |
|
|
Drugs similar to Cyclophosphamide
|
-Chlorambucil
-Melphalan -Ifosphamide -Nitrogen mustard -Musulfan |
|
|
Vinca Alkaloids
|
-Vincristine
-Cell cycle specific: causes mitotic arrest in M-phase of cell division -Binds to tubulin and disrupts formation of mitotic spindle -Metabolized via hepatic clearance --careful in patients with liver failure or reduced liver fxn |
|
|
Indications for Vincristine
|
-Combination protocols
-Lymphoma -Leukemia -TVT (most effective drug in TVT) -Sarcomas |
|
|
Vincristine Toxicity
|
-Moderate to severe bone marrow and GI toxicity
-Peripheral neuropathy via axonal degeneration --decreased proprioception, pins and needle sensations -Causes Ileus and GI standstill -Some dogs are uniquely sensitive to vincristine --causes sepsis in dogs with lymphoma -Not a benign drug! |
|
|
Methotrexate
|
-Anti-metabolite
-Cell-cycle specific for S-phase -Inhibits dihydrofolate reductase --prevents folate metabolism, no formation of purines and pyrimidines -Excreted via kidneys -Used for lymphomas and leukemias |
|
|
Methotrexate Toxicity
|
-Bone marrow
-GI |
|
|
Cytosine Arabinoside
|
-Anti-metabolite
-Cell-cycle specific, S-phase arrest -Cytosine Incorporates into DNA and inhibits DNA template function --slows chain elongation --competitive inhibitor of DNA polymerase -Metabolized via kidneys -Use for lymphomas and leukemias -Can cross BBB, effective for brain cancers |
|
|
Cytosine Arabinoside Toxicity
|
-Bone marrow and GI
|
|
|
Cisplatin and Carboplatin
|
-Platinum agents
-Cell-cycle non-specific -DNA breaks through inter and intra-strand cross-links -In cell, Cisplatin and Carboplatin are the same drug -Renal excretion -Use for osteosarcomas, carcinomas, and rescue in lymphomas -DO NOT give Cisplatin to patients with decreased renal function and decrease the carboplatin dose |
|
|
Cisplatin and Carboplatin Toxicity
|
-Cisplatin: renal toxicity
--need to diuresis patients --Moderate Bone marrow toxicity --acute emesis --GI --Neurologic --NEVER GIVE CISPLATIN TO CATS -Carboplatin: Bone marrow and GI |
|
|
L’Asparaginase
|
-Enzyme therapy
-Oldest chemotherapy drug in vet medicine -Targets deficiency in lymphoid malignancies, cannot produce L’Asparganine --lymphoid cells lack L’Aspargagine synthase -Cell-cycle specific for G1 phase -Enzymatic degradation of L’Asparagine depletes extracellular stores of L’Asparagine, causes cell death -Use for Lymphomas and lymphoblastic leukemias -Enzyme, is broken down via enzymatic degradation and immune clearance |
|
|
L’Asparginase Toxicity
|
-Anaphylactic/allergic reactions
-Decreased protein synthesis -Pancreatitis (not significant) |
|
|
Chemotherapy Dosing
|
-based on body surface area, accurate and consistent dosing that correlates with energy expenditure and CO
-Predictable and repeatable drug concentrations -BSA calculation is based on K value --K=10.1 in dogs --K=10.0 in cats -K value does not take into account variation in size, shape, breed of animals --leads to under-dosing in large dogs and over-dosing in large dogs |
|
|
Issues with BSA based Dosing for Chemotherapy
|
-Does not take into account extreme variation between breeds in terms of body conformation and weight
-Leads to over-dosing of small dogs and under-dosing of large dogs -Small dogs are dosed per body weight in KG for some drugs -May need to adjust with obese patients and patients with organ dysfunction -BSA is a good starting point, but should be re-assessed and adjusted according to response and toxicity --make incremental increases if no toxicity or disease shows up |
|
|
Guidelines for Combination Chemotherapy
|
-Better than a single agent of chemotherapy
-Combine drugs with single agent activity, concomitant, or sequential dosing -Combine drugs that do not have over-lapping toxicity -Use drugs with different mechanisms of action to give broader anti-cancer activity -Treat at short intervals -Include drugs that are not affected by multi-drug resistance --do not use drugs that show resistance! |
|
|
Dose Intensity
|
Reflects total dose given at one point in time
-mg/m2 |
|
|
Dose Density
|
-Reflects frequency of drug administration
-mg/m2/week |
|
|
High dose density/intensity
|
-May have theoretical advantage
-higher doses of drugs are given over short time periods --kills more cells and allows shorter time for tumor cell recovery between treatments -Dose intensity is relative, depends on how individual patient metabolizes a drug -Can look at side-effects to indirectly measure dose intensity --neutropenia -Optimal anti-tumor effect is observed when some toxicity is observed in normal tissues |
|
|
Chemotherapy and “No Pain No Gain”
|
-Dogs with toxicity that require dose reduction with treatment delay do better than no toxicity and treatment delay
-indicates that a little toxicity is good -No toxicity, probably too low on dose-response curve |
|
|
Guidelines for adjusting Chemotherapy Dose
|
-Reduce dose 20-25% in patients with serious toxicities
--GI myelosuppression, sepsis -With neutropenia (less than 2,000), delay treatment until recovery -Asymptomatic neutropenia (1200-1800), no dose reduction but consider prophylactic antibiotics to prevent infection -Severe neutropenia (less than 1200) dose reduction 10-20% according to severity of toxicity -No toxicity or myelosuppression, consider increasing dose gradually |
|
|
Chemotherapy Toxicities
Acute side effects |
-Self-renewing tissues
-Bone marrow -GI -Mucosae -Hair follicle -Gametes -Affect stem cells that have full renewing ability, will see full recovery |
|
|
Chemotherapy Toxicities
Chronic Side Effects |
-Static tissue
-No self-renewal capacities -Connective tissue -Nerves -Muscles -Permanent, no or limited recovery |
|
|
Tissues affected by acute toxicity
|
-Tissues with self-renewing capacity
-Bone marrow -GI epithelium -Mucosal epithelium (rare in dogs and cats) -Gametes -Hair follicles in breeds with continuous hair growth |
|
|
Therapeutic index for Acute Toxicity
|
-Narrow therapeutic index
-Optimal anti-cancer effects -Moderate side effects to normal tissue -Acute side effects on normal tissue limites the dose |
|
|
Myelosuppressive drugs and protocols
|
-Doxorubicin
-Vinblastine/Vincristine -Cyclophosphamide -Actinomycin D -Carboplatin -Mitoxantrone -Combination protocols |
|
|
Myelosuppression and Chemotherapy
|
-Neutrophils are most susceptible
--have shortest half-life -Platelets have a little longer halflife, will see thrombocytopenia -RBCs are affected the least, long half-life --should not see acute anemia in a cancer patient due to chemotherapy -Monitor CBC 7-10 days post chemotheraphy -If effect is seen, delay treatment until there are signs of recovery -Reduce the dose for the next cycle if there are severe clinical signs or neutrophil count less than 1200 |
|
|
Treatment for Myelosuppression
Asymptomatic animals |
-Prophylactic oral antibiotics
--trybrissen, baytril -Monitor for fever or signs of sepsis |
|
|
Treatment for Myelosuppression
Symptomatic animals |
-Hospitalize for supportive care
-IV fluids -Combination of broad-spectrum antibiotics -Full recovery is expected in most cases -C-GSF is rarely needed, usually get rapid recovery of bone marrow stem cells |
|
|
GI toxicity with chemotherapy
|
-Acute toxicity to basal epithelial cells
-Intestinal wall sloughs superficial cells -Signs: diarrhea, vomiting, decreased appetite --decreased quality of life -Breakdown of intestinal wall integrity can permit translocation of GI bacteria and lead to sepsis |
|
|
GI Chemotherapy toxicity Treatment
|
-Anti-emetics: prophylactic with certain drugs and drug combinations
-GI protectants -Antibiotics if there is melena or concominant neutropenia -Mild/moderate toxicity treat with oral drugs, dietary modification -Sever toxicity: hospitalization and IV fluids, anti-emetics, antibiotics |
|
|
Anti-emetics
|
-Odansetron/Dolasetron: serotonin receptor antagonist
-Cerenia: maropitant citrate, NK-1 receptor blocker -Metoclopramide: blocks CRTZ --dopamine antagonist, serotonin antagonist -Butorphanol: narcotic analgesic and standard anti-emetic with cisplatin -Corticosteroids |
|
|
Vesicants and Chemotherapy
|
-Many drugs are extreme vesicants
-Need proper technique and catheter placement -Need experienced nurses -DO NOT let chemotherapeutic drugs go outside of the vein! |
|
|
Alopecia and Chemotherapy
|
-Not an issue in most breeds
-Aesthetic only, not a clinical issue -Temporary hair loss -Sometimes may have changes in hair color |
|
|
Risks for Chemotherapy Side Effects
|
-Usually occurs early in the treatment phase
-Most common in lymphomas and less common in solid tumors -More common in small dogs than larger dogs -Docorubicin and Vincristine -Concurrent disease can decrease drug clearance -Goal is NOT to avoid toxicity at all cost --“no pain no gain” |
|
|
Chemotherapy drug resistance
|
-Big problem, major obstacle in curing patients with cancer
|
|
|
Relative resistance to chemotherapy
|
-Can be overcome with dose intensification
-May lead to absolute resistance -More common in vet medicine |
|
|
Absolute resistance to Chemotherapy
|
-De Novo resistance or acquired
-Cells have inherent mechanisms that protect tumor cells against effects of chemotherapy -Multi-drug resistance affects many different drugs -Defective checkpoint function, tolerance of cell to DNA damage -Defective or loss of tumor suppressor genes and apoptotic response to irreparable DNA damage |
|
|
Mechanisms in Chemotherapeutic Drug resistance
|
-Decreased uptake of drug
-Decreased activation of drug -increased inactivation of drug -alteration of target enzyme -Rapid repair -Increased efflux of drug |
|
|
Multi-drug Resistance with Chemotheraphy and Tumors
|
-Many chemotherapeutic agents are derived from trees, plants, fungi, “natural toxins”
-Multi-drug resistance confers resistance to natural cancer drugs -Cell encodes for expression of P-glycoprotein --cell membrane pump that excretes xenobiotics, natural toxins --part of cell’s natural defense system, expressed in normal tissue -DE-novo expression is associated with poor response to chemotherapy and shorter survival |
|
|
Strategies for avoiding chemotherapeutic resistance
|
-Use maximal tolerated dose
-Treat for short intervals, allow for recovery of normal affected tissues -Use combination protocols for broad anti-cancer efficacy -include at least 1 drug that does not have multi-drug resistance in combination protocols |
|
|
Factors determining Chemotherapy treatment approaches
|
-Goal is to cure or prolong life, or palliate |
|
|
Platelet disorders
|
-Thrombocytopenia
-von Willebrand Disease -Thrombopathia -Thrombocytosis |
|
|
Surface Bleeding
|
-Petechia
-Ecchymosis -Epistaxis -Melena -Hematuria Indicates primary hemostatic defect -Platelet defect |
|
|
Cavity Bleeding
|
-Hematoma
-Hemarthrosis -Hemoperitoneum -Hemothorax -Hemomediastinum Indicates secondary hemostatic defect -Coagulation defect |
|
|
Low platelet count in otherwise normal dog
|
-Repeat platelet count to be sure
-Recheck with fresh sample -Clean venipuncture is essential |
|
|
How to do a platelet count
|
-EDTA or citrate tube (purple top or blue top)
-Clean venipuncture is essential! -Always evaluate blood smear AND automated platelet count -Verify questionably low platelet counts by repeating with a fresh sample |
|
|
Jugular venipuncture
|
-Avoid in patients with suspected hemostatic disorders
-Jugular hematoma can press on trachea and interfere with breathing |
|
|
Congenital Macrothrombocytopenia
|
-Asymptomatic decrease in the number of platelets
-Severe thrombocytopenia (less than 30,000) --repeatedly continually low -Macrothrombocytes are common, big platelets -Bleeding is NOT observed -Missense mutation in beta-tubulin gene -Inherited as autosomal recessive trait -Occurs in CKCS -Need to do DNA testing to be sure of diagnosis |
|
|
Congenital Macrothrombocytopenia Breed predisposition
|
-Chihuahua
-Labrador retriever -Poodle -English toy spaniel -Shih Tzu -Maltese -Jack russel -Havanese |
|
|
Factors contributing to Thrombocytopenia
|
-Decreased production: Bone marrow issue
--neoplasia --drug interaction -Increased sequestration: spleen --splenic torsion or neoplasia -Increased consumption --DIC -Increased destruction: IMTP |
|
|
Babesia gibsoni
|
-RBC parasite
-Causes thrombocytopenia |
|
|
Infectious diseases causing thrombocytopenia
|
-Ehrlichia
-Babesia -Anaplasma phagocytophilum -Bartonella -Rickettsia rickettsia -Leptospira -Dirofilaria immitis -Leishmania |
|
|
Diagnosing Infectious agents causing thrombocytopenia
|
-Blood smear
-Serology -PCR |
|
|
Immune-mediated Thrombocytopenia
|
-Primary: autoimmune disorder
--ITP -Secondary: antibody formation due to antigenic stimulus --drugs (sulfas, cephalosporins) --Infectious disease (Ehrlichia, babesia) --Neoplasia |
|
|
Immune-mediated Thrombocytopenia Clinical Signs
|
-Surface bleeding
--petechia, ecchymosis, epistaxis, ocular hemorrhage --Hematuria --GI bleeding -Fever -Splenomegaly -Anemia (or PVC may be totally normal) -Bleeding may be mild |
|
|
Diagnosis of Immune-mediated Thrombocytopenia
|
-Severe thrombocytopenia may be only laboratory finding (less than 30,000)
-Diagnosis of exclusion, rule out other possible causes of thrombocytopenia |
|
|
Testing for Immune-mediated Thrombocytopenia
|
-Diagnosis of exclusion
-Serum chemistry screen -Urinalysis -PT/PTT -Serology and PCR for infectious diseases -Thoracic radiographs -Abdominal ultrasound |
|
|
Bone marrow Aspirate for Immune-mediated Thrombocytopenia
|
-Used for prognosis, not for diagnosis
-Normal to increased megakaryocytes -Platelet destruction, consumption, or sequestration in periphery -Decreased number of megakaryocytes --drug or toxin --infection --neoplasia --immune-mediated disorder |
|
|
Bone Marrow Aspirate locations
|
-Dog/Cat:
--Iliac Crest --Humerus -Horse/Ruminants: --dorsal 3rd of the rib --Tuber coxae in the foal --sternum in the adult |
|
|
Immune-mediated Thrombocytopenia Treatment
|
-Remove triggering agent or treat underlying disease
-Doxycycline -PRBC transfusions -Platelet transfusions -Immunosuppressive drugs -Try to treat underlying disease before using immunosuppressive drugs |
|
|
Blood Transfusions with Immune-mediated Thrombocytopenia
|
-Packed red blood cell (PRBC): give O2 carrying support with severe anemia
-Platelets may be destroyed after administration, will not increase platelet count -Platelet transfusions only in severe, uncontrolled, life-threatening bleeding |
|
|
Corticosteroids for Immune-mediated Thrombocytopenia
|
-Decrease platelet clearance
-Modify platelet/Antibody interaction -Decrease antibody production -Suppress inflammatory response |
|
|
Complications with Corticosteroids and IMT
|
-Iatrogenic hyperadrenocorticism
-Secondary infections in skin or urine -Thromboembolic disease -GI ulceration (uncommon) -Treatment can make animal worse! |
|
|
Vincristine for Immune-mediated Thrombocytopenia IMT
|
-Vinca alkaloid binds to tubulin
-Impairs macrophages -Stimualtes megakaryocyte release from bone marrow -Stimualtes thrombopoiesis -Insignificantly impairs platelet function also |
|
|
Vincristine IMT toxicity
|
-Perivascular sloughing
-Peripheral neuropathy -Myelosuppression (uncommon) |
|
|
Prednisone and Vincristine ITP treatment
|
-Shortens duration of severe thrombocytopenia
|
|
|
Treatment options for ITP/IMT
|
-Cyclosporine
-Azathioprine -Mycophenolate -Leflunomide -Danazol -Human IV immunoglobulin -Splenectomy |
|
|
ITP/IMT Prognosis
|
-Excellent prognosis if there is a rapid response to therapy
-Duration of therapy: 4-6 months -Check platelet count 7-10 days after each dose reduction --Do not taper treatment too quickly, ending too early may cause relapse -If there is decreased megakaryocytic activity, guarded prognosis |
|
|
Von Willebrand Disease
|
-Most common hereditary bleeding disorder in the dog
-Also reported in pigs, horses, cattle, cats -Deficiency of vWF causes impaired platelet adhesion -Platelets are fine, animal lacks vWF that supports adhesion of platelets to vessels -Especially occurs in areas with increased shear force of blood |
|
|
Von Willebrand Factor
|
-Synthesized and stored in vascular endothelial cells
-Negligible amount in canine platelets -Multimeric structure -Allows for platelet adhesion to blood vessel subendothelium -Carrier for factor VIII |
|
|
Type I von Willebrand Factor Disease
|
-Low vWF concentration
-Normal structure, all multimer sizes are proportionally reduced -All multimers are present, just in reduced amounts -Most common form -Severity of bleeding is variable, not always correlated with amount or lack of vWF |
|
|
Type II von Willebrand Factor Disease
|
-Low vWF concentration
-Disproportionately low vWF activity due to deficiency of high-molecular weight multimers |
|
|
Type III von Willebrand Factor Disease
|
-Complete vWF deficiency
-Less than 1% plasma vWF |
|
|
Feline von Willebrand Disease
|
-2 case reports in literature
-Extremely rare! |
|
|
Von Willebrand Disease Clinical Signs
|
-Mucosal surface bleeding
-Excessive hemorrhage after surgery or trauma -Petechiae are not seen -Severity of bleeding does not always correlate to amount or lack of vWF -Dogs with type II and III usually experience most severe bleeding |
|
|
Screening tests for vWF
|
-Buccal mucosal bleeding time
-Plasma vWF concentration ELISA -DNA testing |
|
|
Buccal mucosal Bleeding Time
|
-Tests for primary hemostasis, does not test clot formation
-Makes standard incision 5mm long and 1mm deep -should clot in less than 4 minutes in dogs, less than 2 minutes in cats --anything more than normal is “prolonged” -Test for: --thrombocytopenia --vWF deficiency --thrombocytopathia --vascular disorders -If know dog has thrombocytopenia, not worth doing, does not give any new information |
|
|
Plasma vWF concentration
|
-Test with ELISA, measure plasma levels of vWF
-Citrate or EDTA blood, anti-coagulated -normal: 70-180% -non-discriminatory: 50-69% -Affected: less than 50% -Severe, type III: less than 1% -Less than 35% is associate with increased risk of bleeding |
|
|
Management of bleeding in von Willebrand Disease patients
|
-Desmopressin
-Blood component therapy |
|
|
Desmopressin
|
-Therapy for von Willebrand Disease
-shortens buccal mucosal bleeding time -Controls clinical bleeding -Give SQ, once per day only -Short hemostatic effect, less than 4 hours -May be administered before surgical procedures or to control minor bleeding -Response is variable, not all dogs respond -Cryoprecipitate and compatible RBCs should be on-hand if needed -Not a long-term solution |
|
|
Blood Component Therapy for vWD
|
-Cryoprecipitate
-fresh frozen plasma -fresh whole blood |
|
|
Cryoprecipitate therapy
|
-Use for vWD and hemophilia A
-Made from fresh frozen plasma -Contains: --vWF --factor VIII --Fibrinogen --fibronectin --factor XIII |
|
|
Administering Cryoprecipitate
|
-Initial dose of 1 unit per 10kg body weight
-Prophylactic use before major surgery --if plasma vWF is less than 35% and dog has bleeding issues -Administer immediately pre-operatively -May need to repeat infusions in 12 hour intervals |
|
|
Platelet Functions
|
1. Adhesion: sticks to vessel wall via vWF
2. Aggregation: sticks to other platelets via fibrinogen 3. Secretion: vesicle release of ADP and serotonin 4. Procoagulant activity: promotes thrombin generation via phospholipid in membrane |
|
|
Scott Syndrome
|
-Platelet procoagulant deficiency
-Occurs in German shepherds -Inherited as autosomal recessive trait -Presents as post-operative hemorrhage, epistaxis, soft tissue hemorrhage -Animal can bleed a lot, need fresh platelets to control bleeding -Routine hemostatic tests are normal -Dx based on prothrombin consumption assay or flow cytometry assay of annexin-V binding |
|
|
Thrombopathia treatment
|
-Does not matter what type
-Fresh platelets to control the bleeding -Fresh whole blood transfusion --animal probably needs RBCs --also needs functioning platelets! |
|
|
Glanzmann Thrombasthenia
|
-Absence or marked reduction in platelet glycoprotein complex IIb/IIIa (fibrinogen receptor)
-Missing fibrinogen receptor --no cross-links formed between platelets -Occurs in otterhounds and great Pyrenees -Inherited, autosomal recessive trait -Severely impaired platelet aggregation -Marked bleeding tendency |
|
|
Glansmann thrombasthenia in Horses
|
-Deficiency in fibrinogen receptor on platelets
|
|
|
Thrombopathia Diagnosis
|
-Appropriate bleeding history
-Platelet count is normal -PT/PTT is normal -Buccal mucosa bleeding time is normal or prolonged -Plasma vWF is normal |
|
|
Indications for Platelet transfusions
|
-Thrombocytopenia |
|
|
Response to Platelet transfusions
|
-Increase in platelet count post-transfusion |
|
|
Tumors in the Skin
|
-Any normal structure in the skin can become neoplastic
--think about anatomy and what is there -Peripheral nerve sheath tumors -Lipoma and liposarcoma -Fibroma and fibrosarcoma (collagen) -Adenomas and carcinomas (apocrine glands) |
|
|
Neoplasia
|
-Formation or presence of a new, abnormal growth of tissue
|
|
|
Hamartoma
|
-Mass of disorganized tissue indigenous to a site
|
|
|
Dysplasia
|
-Lack of uniformity of individual cells
-Loss in architectural orientation -Can be a pre-malignant condition |
|
|
Types of Round Cell Tumors
|
-Lymphocytic
-Histiocytic -Mast cell -Plasma cell -TVT |
|
|
Components of the Epidermis
|
-Keratinized stratified squamous epithelium
-Keratinocytes (85%) -Langerhans cells (3-8%) -Melanocytes (5%) -Merkel cells (2%) |
|
|
Components of the Dermis
|
-Collagen, blood vessels, nerves, lymphatics
-Resident inflammatory cells --mast cells, lymphocytes, dendritic cells, plasma cells -Adnexal structures --hair follicles --epitrichial apocrine glands --sebaceous glands --arrector pili muscles |
|
|
Components of the Subcutis
|
-Adipose tissue
-Skeletal muscle -Collagen -Blood vessels and lymphatics |
|
|
Cytology for Skin masses
|
-Easy to do, can be done in a clinic
-Safe for the patient -Affordable for the client -Gives information immediately --inflammation, infection, neoplasia --benign or malignant --medical vs. surgical management --prognosis |
|
|
Inflammation on cytology
|
-Leukocytes are more than normal
-Leukocyte types present suggest etiology |
|
|
Neoplasia on cytology
|
-Few if any inflammatory cells
-Spindle-shaped cells: mesenchymal --cells blend into each other -Round cells -Epithelial tumor cells associate with each other --can see distinct margins of cells -Look for criteria of malignancy --mitotic figures, anisosyctosis |
|
|
Papilloma appearance and cytology
|
-Exophytic, well-demarcated, verrucus
-Cytology: --keratinocytes --normal squamous differentiation --does not look like much on cytology |
|
|
Neoplasms of the Epidermis
|
-Papilloma
-Squamous cell carcinoma -Bowen’s disease --tumor within epithelium that has not penetrated the basement membrane zone --multicentric squamous cell carcinoma in situ |
|
|
Viral Papilloma
|
-Benign
-Species specific -Exophytic proliferation of epidermis -Verrucous -Caused by infection with papillomavirus -Spontaneous regression due to cell-mediated immune response -Occurs in young dogs or immunosuppressed dogs |
|
|
Squamous Cell Carcinoma Fine Needle Aspirate
|
-Clustered and individualized cells
-Round to polygonal in shape -Some are keratinized -Retained immature nuclei -Vacuoles over the nuclei -May or may not have inflammation -May or may not have bacterial infection -cells will have distinct margins |
|
|
Squamous Cell Carcinoma
|
-Malignant neoplasia of keratinocytes
-Most commonly in cats -Due to prolonged exposure to UV light -exacerbated by lack of pigment or lack of hair/sparse hair coat -Invasive, metastasizes to lymph nodes and lungs |
|
|
Squamous Cell Carcinoma treatment
|
-Remove tumor
-Keep animal out of sun -Check lymph nodes --carcinomas metastasize via lymphatics |
|
|
Subungual Squamous Cell Carcinoma
|
-Occurs in Dogs only
-Malignant neoplasm of the nailbed epithelium -Single digit or multiple digits on the same dog -Often results in loss of the nail with secondary infection to the nailbed -Destruction of the P3 bone by infiltrating neoplasm --total destruction, complete lysis -Must amputate the digit -Metastasizes to local lymph nodes -Dog will present lame with a swollen digit |
|
|
Multicentric squamous cell carcinoma in situ
|
-tumor of very old cats
-Presents with multifocal scaly plaques --old cats with multiple scaly plaques -Bowen’s like disease -Most often “in situ” but can become invasive -Not associated with extended exposure to UV light -Papillomavirus induced in cats -Very rare in dogs |
|
|
Follicular Neoplasms
|
-Neoplasms with adnexal differentiation
-Infundibular keratinizing acanthoma (common) -Trichoblastoma (common) -Trichoepithelioma (common) -Malignant trichoepithelioma (rare) -Pilomatricoma (less common) -Malignant pilomatricoma (rare) |
|
|
Keratin Inclusion Cyst
|
-Tumor is in dermis but sticks out into epidermis
-Can “pop” and get stuff out of cyst |
|
|
Cytology of Keratin Inclusion Cyst
|
-Cytology cannot differentiate cysts, gives non-specific diagnosis
-Cornified squamous epithelial cells --aggregates and individual keratin “bars” -When ruptured, stimulate foreign body reaction in skin |
|
|
DDx for Keratin Inclusion Cyst
|
-Intracutaneous cornifying epithelioma
-Epidermal inclusion cyst -Trichepithelioma |
|
|
Infundibular keratinizing acanthoma
|
-Benign cyst neoplasm
-Shows differentiation to the squamous epithelium of follicular isthmus -Only affects dogs -Quite common |
|
|
Trichoblastoma
|
-Benign neoplasm in hair cells of dogs
-Arises on heads -Derived from or shows differentiation to the hair germ of the developing follicle -Can occur in cats also, mostly dogs though |
|
|
Basal cells of Trichoblastoma
|
-Tightly packed clusters
-Little cytoplasm -Dense, round nucleus -Uniform, bland looking -Cytologically cannot tell the difference between trichoblastoma and basal cell tumor |
|
|
Trichoepithelioma
|
-Benign neoplasm
-Differentiation of all 3 segments of the hair follicle -Incomplete or abortive trichogenesis is present -Common in the dog --basset hounds are at increased risk -Form little cysts, cysts are filled with hair follicles |
|
|
Sebaceous gland tumors
|
-Very common
-Firm, white papules -Senile sebaceous gland hyperplasia -Adenomas -Sebaceous epitheliomas (can be unpredictable, usually are benign) --usually benign if on the back of the animal -Carcinomas: potential for widespread metastasis --usually occur on ears and head -If sebaceous gland tumors ulcerate, remove! |
|
|
Meibomian gland neoplasia
|
-Modified sebaceous glands on inner aspect of the eyelid
-Adenomas -Epitheliomas -Carcinomas -Remove, can cause damage to the eye |
|
|
Hepatoid gland neoplasia
|
-Perianal modified sebaceous gland neoplasia
-Occur on anal margin in intact dogs -only in dogs -Often Androgen mediated, can neuter and tumor will regress -Usually benign -Adenomas -Carcinomas -Epitheliomas |
|
|
Sebaceous gland neoplasia cytology
|
-Can be hard to aspirate
-Cells are in clusters -Distinct borders to the cells -Abundant cytoplasm -Highly vacuolated, foamy cytoplasm |
|
|
Sebaceous gland neoplasia DDx
|
-Sebaceous hyperplasia
-Sebaceous adenoma |
|
|
Sebaceous Hyperplasia
|
-NOT a papilloma
-Senile nodular sebaceous hyperplasia -Localized intradermal increase in size and number of sebaceous glands -Causes overlying epidermis to bulge outwards |
|
|
Cytology of Perianal gland adenomas/Hepatoid gland tumors
|
-Clusters of large, polygonal cells
-Big lavender cytoplasm -Central round nucleus -Smaller “reserve” cells are interspersed |
|
|
Hepatoid gland location
|
-Perianal region
-Dorsal and ventral aspects of the tail -Parapreputial area in males -Abdominal mammary region in females |
|
|
Apocrine and modified apocrine gland tumors
|
-Apocrine adenoma
-Apocrine carcinoma -Ceruminous adenoma -Ceruminous carcinoma -Anal sac glad carcinoma |
|
|
Chronic unilateral otitis
|
-Young animal: polyp
-Old animal: neoplasia -Ceruminous gland tumors are most common --ceruminous gland carcinoma in cats --ceruminous gland adenoma in dogs |
|
|
Histiocyte
|
-Fixed tissue macrophage, antigen presenting cells
-Langerhan’s cells in epidermis -Dermal dendritic cells in dermis -Give rise to histiocytic neoplasms |
|
|
Histiocytoma
|
-“Surgical emergency”
--if you don’t operate you will lose money because tumor will regress on own -Benign -Occurs in dogs |
|
|
Reactive Histiocytosis
|
-Proliferation of dermal dendritic cells
-“Reactive,” not benign -IN dogs only -Cutaneous form -Systemic form that can affect internal organs |
|
|
Histiocytic Sarcoma
|
-Unknown cell type
-Soft tissue mass that destroys the joints of dogs --most commonly affects elbows -Can affect many internal organs -In disseminated form: malignant histiocytosis |
|
|
Ceruminous gland Neoplasia
|
-Can be benign or malignant
-Cerunimous gland adenoma (benign) are common in both dogs and cats -Ceruminous gland carcinoma (malignant) --more common in cats --infiltrative neoplasia, rarely invade or destroy the cartilage of the ear canal -If invades the dermis and lymphatics, will spread to parotid lymph node -Have to do histopathology |
|
|
Cytology of Anal Sac gland Carcinoma
|
-Indistinguishable from other tumors of apocrine cells
-Cytologic appearance does not predict biologic behavior -Produces PTH-like hormone that releases Ca from bone and increase Ca concentration in blood |
|
|
Anal sac gland Carcinoma
|
-Malignant neoplasm
-arises from apocrine epithelium in walls of anal sacs -Can appear as perianal mass -Impossible to differentiate from hepatoid gland neoplasms -Can physically obstruct rectum, results in straining and difficulty defecating -Some cases will develop PU/PD, weakness, hypercalcemia due to PTH-like hormone production by neoplastic cells -Neoplastic cells can infiltrate the vertebral column |
|
|
Cutaneous Round Cell Neoplasms
|
-Mast cell
-Histiocytic -Lymphosarcoma --epitheliotrophic and non-epitheliotrophic -Plasma cell -Transmissible venereal tumor (TVT) |
|
|
Mast cell neoplasia
|
-Ubiquitous in domestic animal species
-Focal or multi-centric in the skin -Can involve viscera (spleen, liver, intestine) -Variation in behavior and location based on species |
|
|
Canine mast cell neoplasia
|
-Skin is most common site
-Highly variable gross appearance --can look like ANYTHING -Erythematous, alopecic, edematous masses or plaques -Ulceration is common in larger neoplasms |
|
|
Cytology of Canine Mast Cell Tumors
|
-May be bloody
-Round cells will be highly granulated -Round nuclei with pale staining, nuclei will be obscured by granules -Inflammation --eosinophilic inflammation is common --Neutrophils and bacteria with ulceration -Need to make sure the slide is stained properly! |
|
|
Feline Mast Cell Neoplasia
|
-Less common compared to mast cell neoplasia in dogs
-Mostly in cats more than 4 years old -Siamese cats are at high risk -Papules, plaques, or nodules -Multiple neoplasms -Ulceration can be seen in larger lesions |
|
|
Cytology of feline mast cell tumor
|
-May be bloody
-Round cells highly granulated -Nuclei will be obscured by granules -Granules may be finer -No eosinophilic inflammation |
|
|
Cytology of Canine Histiocytoma
|
-Round cells with bland, round nuclei
-may or may not have small nucleoli -Moderate cytoplasm -Pale cell borders -Mitoses may be common -May have inflammation --neutrophils with ulceration --lymphocytes with regression |
|
|
DDx for canine histiocytoma
|
-Lymphoma
--carries very different prognosis!!! -Plasmacytoma -TVT |
|
|
Histiocytic tumors
|
-Canine cutaneous histiocytoma (most common)
-Reactive histiocytosis/cutaneous histiocytosis -Systemic histiocytosis --affects skin and internal organs -Langerhans cell histiocytosis (very rare) -Histiocytic sarcoma |
|
|
Canine Cutaneous Histiocytoma
|
-Langerhans cells
-Benign neoplasm is very common -Typically occurs in dogs less than 4 years old --in older dogs tumor is less likely to go away on own -Purebred dogs are predisposed -“button” neoplasm, smooth pink raised mass covered by alopecic skin -Ulceration is common -Usually focal, only one -Complete excision is curative, often go away on own |
|
|
Reactive Histiocytosis
Cutaneous histiocytosis |
-Nodular cutaneous proliferation of histiocytes
-Waxes, wanes, and regresses spontaneously -Multiple nodules, single nodules, coalescing nodules -Nodules are covered by epidermis -Lesions can appear anywhere on the skin -Usually appear on face and planum nasale -If on planum nasale can cause difficulty breathing |
|
|
Cytology of histiocytic proliferative disorders
|
-Cells may be pleomorphic
-Phagocytotic activity is possible -Mitoses may be frequent -May or may not have inflammation |
|
|
DDx for Histiocytic proliferative disorders
|
-Atypical histiocytoma (single mass)
-Reactive histiocytosis (multiple masses) -Systemic histiocytosis (internal organ involvement -Histiocytic sarcoma |
|
|
Systemic Histiocytosis
|
-Multicentric cutaneous lesions
-Lesions may wax and wane -Familial in Bernese mountain dogs -Skin, eyelids, sclera are often involved -Lymph nodes, lungs, spleen, bone marrow are affected in later stages of disease -Need continuous immunosuppression to treat |
|
|
Histiocytic Sarcoma
|
-Highly malignant round cell neoplasm in dogs
-Most often in Rottweilers, goldens, and Bernese -Lesions on skin can be single, multiple, solitary, clustered -Can be on skin only or as part of multi-organ disease -Often involves viscera --spleen, liver, lung, kidney, lymph nodes, periarticular tissue |
|
|
Histiocytic Sarcoma Histology
|
-Can be indistinguishable from other sarcomas
-Big cells with multiple nucleoli -Vacuoles -Cells are round to spindle shaped -Moderate to abundant cytoplasm |
|
|
Epitheliotropic Lymphosarcoma
|
-Infiltration of neoplastic lymphoid cells into the skin
-Neoplastic Lymphoid cells present in epidermis -exfoliative erythroderma -Patch, plaque, tumor --diffuse red scaly skin -Depigmentation of cells -Poor prognosis |
|
|
Lymphosarcoma Cytology
|
-Round cells
--round nuclei, smudged chromatin, indistinct nucleoli -Little cytoplasm -Dark borders to cells -Mitosis is common -Cells are bigger than neutrophils -Inflammation present --tingible macrophages --neutrophils may have ulceration --eosinophils may be paraneoplastic |
|
|
Plasma cell Neoplasia
|
-Round cell tumors
-Usually de novo proliferations -Unassociated with primary bone marrow neoplasia -Older dogs -Small red, slightly raised dermal nodules -Covered by alopecic or ulcerated skin -Usually on ears, lips, digits, oral cavity, rectum -Benign, NOT associated with multiple myeloma -Do not spontaneously regress, will have to be removed |
|
|
Cytology of Plasma cell neoplasia
|
-Round to oval cells
--eccentric round nucleus -Moderate to abundant cytoplasm -Flame cell has a pink border -Mott cell has vacuoles |
|
|
DDx for Plasma cell neoplasia
|
-Histiocytoma
-Lymphoma |
|
|
Mesenchymal Neoplasia
|
-Fibrous tissue
-Adipose tissue -Vascular tissue -Peripheral nerves -Canine hemangiopericytoma |
|
|
Neoplasia of Fibrous tissue
|
-Fibroma
-Nodular dermatofibrosis (German Shepherds) -Fibrosarcoma -Equine sarcoid -Myxoma/Myxosarcoma |
|
|
Fibroma
|
-Benign neoplasia of fibrocytes
-Abundant collagenous stroma -Most often seen in dogs |
|
|
Nodular Dermatofibrosis
|
-German Shepherds most often, occasionally other breeds
-Multiple fibromas present, 30 or more -Rare -Females are predisposed -May also have renal cystadenocarcinomas or uterine leiomyomas in conjunction with skin lesions |
|
|
Fibrosarcoma
|
-Mostly in adult dogs and cats
--unless cat is affected with FeSV -Mostly focal neoplasms -FeSV neoplasms are multicentric |
|
|
Vaccine-associated fibrosarcoma
|
-Aggressive, recurrent variant of fibrosarcoma
-Firm mass in subcutis or skeletal muscle --cystic center with watery or mucinous fluid -High mortality, poor prognosis -Sends tentacles out edges that can penetrate adjacent tissue -Sarcomas arise at vaccine sites -Need to be removed! -Give vaccines in extremities as distally as possible |
|
|
Cytology of Spindle Cell Neoplasia
|
-Poorly exfoliating mesenchymal tissue
-Individual cells or tangled aggregates with or without a matrix -Oval nuclei with or without nucleoli -Wispy cytoplasm with indistinct borders -Can look like granulation tissue |
|
|
DDx for Spindle Cell neoplasia
|
-Bland: scar tissue, fibroma, hemangiopericytoma, low grade sarcoma
-Inflammation: reactive fibrosarcoma, fibroma or sarcoma -Criteria for Malignancy: Sarcoma |
|
|
Cytology of Vaccine-associated Fibrosarcoma
|
-Many spindle cells
-Criteria of malignancy -May or may not have matrix -Inflammation is common --mast cells --neutrophils, macrophages |
|
|
Equine Sarcoid
|
-Non-productive infection with Bovine Papilloma virus
-Bovine papilloma virus causes SARCOIDS in horses, not papillomas -Occurs in any age horse -Usually seen in horses less than 4 years old -Occurs anywhere on body --esp. head, legs, ventral trunk -40% of affected horses have multiple sarcoids -Can be verrucous, fibroblastic, mixed, or flat -Hard to completely remove, will recur |
|
|
Neoplasms of Peripheral nerves
|
-Neurofibroma: Benign nerve sheath neoplasms
-Neurofibrosarcoma: malignant peripheral nerve sheath neoplasm --can metastasize retrograde |
|
|
Neurofibroma
|
-Benign nerve sheath neoplasm
-Uncommon in cats, occurs mostly on the head -Rare in dogs |
|
|
Neurofibrosarcoma
|
-Malignant nerve sheath neoplasm
-Malignant schwannoma |
|
|
Neoplasia of Adipose Tissue
|
-Lipoma
-Infiltrative Lipoma -Liposarcoma |
|
|
Lipoma
|
-Common benign neoplasm
-Predisposition in female dogs and castrated male cats -Animal may have multiple tumors -Infiltrative lipomas invade muscle and can recur |
|
|
Liposarcoma
|
-Malignant neoplasm of adipocytes
-Most common in dogs -Recurrence is common, metastasis is rare |
|
|
Cytology of fatty tumors
|
-Aggregated round to spindle-shaped cells
-Greasy appearance -Free lipid droplets, clear vacuoles in background |
|
|
Liposarcoma Cytology
|
-Differentiation of adipocytes is variable
-Criteria of malignancy is present -May be indistinguishable from other sarcomas |
|
|
Neoplasms of vascular tissue
|
-Hemangioma
-Hemangiosarcoma -Lymphangioma -Lymphangiosarcoma |
|
|
Hemangioma
|
-Benign neoplasm of vascular endothelium
-Dermal or subcutaneous -Light-skinned short-haired dogs may be predisposed with prolonged exposure to sunlight |
|
|
Hemangiosarcoma
|
-Can be solitary or part of multicentric syndrome
--metastasis from spleen or liver -Can result on skin from solar irritation -Short-haired light-skinned breeds are predisposed (greyhounds, whippets, pit-bulls) -Small percentage of canine neoplasms may represent malignant transformation of hemangiomas |
|
|
Lymphangioma
|
-Benign neoplasm of lymphatic epithelium
-Poorly demarcated dermal masses that are soft and spongy to touch -Often wet on cut surface, exude clear serous fluid -Can be difficult to differentiate from malignant Lymphangiosarcoma -May be congenital, can occur in first few months of life -Occurs in subcutis along ventral midline and limbs |
|
|
Lymphangiosarcoma
|
-Malignant neoplasm of lymphatic epithelium
-Poorly demarcated dermal masses -Wet, soft, spongy to touch -Can be difficult to differentiate from benign lymphangiomas |
|
|
Feline ventral Abdominal Lymphangiosarcoma
|
-Only in cats
-presents as a distinctive lesion on caudoventral abdominal wall -Diffuse bruised appearance, looks like dermal and subcutaneous hemorrhage -Oozes serosanguineous fluid when cut -Can look like a deep fungal or bacterial infection |
|
|
Canine Perivascular Wall Tumors
Hemangiopericytoma |
-Perivascular wall tumors
-Often occur around joints -Common in middle aged or older large-breed dogs -Usually just one, focal multi-lobulated and infiltrative -Arises in subcutis around joints of limbs -Variable appearance --white, gray, red --soft or firm --rubbery to fatty |
|
|
Cytology of Hemangiopericytoma
|
-Spindle cell aggregates
-“Whorling” pattern around capillaries -cells may be bland to pleomorphic -Can look like scar tissue or reactive fibroplasia, fibroma or fibrosarcoma |
|
|
Melanocytoma
|
-Benign lesion on haired skin
-Arises from melanocytes in epidermis, dermis, or adnexal structures --External root sheath of hair follicle -Common in dogs, horses, certain pig breeds -Less common in cats and cows -Rare in sheep and goats |
|
|
Benign vs. Malignant Melanoma Neoplasms
|
-Benign neoplasms tend to arise from haired skin
-Malignant neoplasms arise from mucocutaneous junctions -To determine malignancy, do histology/cytology |
|
|
Malignant Melanoma
|
-Common in the dog, especially in the oral cavity
-Uncommon in other domestic species |
|
|
Cytology of Melanocytic tumors
|
-Variable cytology
-Can look like round cells, epithelial cells, or spindle cells -May only be sparsely pigmented --Pigment appears fine to coarse --can stain golden, brown, blue, or black -Criteria of malignancy is variable, not predictive for tumor malignancy |
|
|
Subungual Malignant Melanoma
|
-Neoplasm arising in epithelium of the nailbed |
|
|
Clinical signs of Anemia
|
-Specific signs:
--Pale mm --Hemorrhage --Icterus -Non-specific signs: --weakness --exercise intolerance --tachycardia or murmur --hypocolemic shock |
|
|
Most common anemia in dogs and cats
|
-Non-regenerative anemia
-Due to toxicity and cancers -Diseases are not specific to hematology but affect the hematological system |
|
|
Compensatory mechanisms to deal with Blood loss
|
1. Redistribution of Blood
2. Increased CO 3. Increased O2 delivery 4. Increased RBC production |
|
|
Redistribution of blood to compensate for blood loss
|
-Rapid peripheral vasoconstriction
-Splenic contraction in dogs --not in cats, spleen is too small to help -Contributes to pallor seen |
|
|
Increased CO to compensate for blood loss
|
-Tachycardia (rapid response)
-Cardiac hypertrophty (slow change) |
|
|
Increased O2 delivery to compensate for blood loss
|
-Reduced Hb-oxygen affinity
-Increased DPG in dogs --promotes rapid release of O2 from Hb --occurs in dogs and humans only |
|
|
Causes of Anemia
|
-Reduced O2 carrying capacity of blood
-Reduced blood volume -Underlying disease -Compensatory mechanisms -Clinical signs are influenced by severity, onset time, type, and underlying disease |
|
|
Advantages of in-clinic testing of blood
|
-Emergency situations
-peri-operative situations -Appropriate and rapid intervention or therapy -Allows for direct communication with client about diagnosis, prognosis, and treatment |
|
|
EDTA
|
-Most important blood sample for hematologic testing
-Serum is not a good sample, clots and RBCs are not preserved -Citrate is not common -Heparin can be used, not common |
|
|
In-clinic Lab tests
|
-PVC or Hb
-TP -Plasma color -Blood smear -Urinalysis -Fecal -Glucose -BUN |
|
|
Instruments needed for in-clinic lab testing
|
-Microscope
-Refractometer -Microcentrifuge -Serofuge -Dipsticks -Various kits |
|
|
Packed Cell Volume
|
-AKA Microhematocrit
-normal dogs: 37-55% -Normal cats: 30-48% -Calculate from MCV and RBC count -Hematocrit is calculated from machine |
|
|
%Hb in RBCs
|
30%
1/3 of RBC is Hb -Can calculate PCV if you know Hb --multiply by 3 -Hb measurement is one of the most accurate to do --not affected by leykocytosis |
|
|
3 minute blood smear examination
|
-Microscopic evaluation is required for proper assessment!
-Confirm RBC, WBC, and Platelet values -Assess WBC differential for diseased animals -Identify morphological abnormalities |
|
|
RBC abnormalities
|
-Polychromasia
-Anisocytosis -Changes in cell shape -Blood organisms -Agglutination |
|
|
WBC abnormalities
|
-Toxic changes
-Inclusions -Granulations -Bacteria |
|
|
Platelet abnormalities
|
-Platelet clumps
-Pseudocytopenia -Macroplatelets -Granulation or inclusion |
|
|
CBC sample collection
|
-Collect a sample regardless of what you are going to do, just in case
-Collect before treatment if possible -EDTA tube and any needle -Immediately invert 10x -Ensure adequate ratio of blood to EDTA -Sample should be free of clots and platelet clumps -Can stay several hours at room temp --24 hours if refrigerated -Blood smears should be prepared on fresh blood sample -LABEL SAMPLE! |
|
|
Reticulocytosis
|
-Best parameter to measure a regenerative RBC response
-Will not see reticulocytes on a blood smear, have to stain -Polychromasia is visible on blood smear -Reticulocyte stain shows RNA within RBC |
|
|
Best parameter to identify RBC regeneration on a blood smear
|
-Polychromasia
-Cannot see reticulocytes on blood smear, need special stain -Nucleated RBCs are NOT a good parameter for regeneration --poor indicator of regeneration |
|
|
Regenerative Bone marrow Response
|
-Reticulocyte count is best parameter
--Stain and count aggregates -Aggregates correlate with polychromasia -% reticulocytes in 500 cells -% corrected reticulocytes based on PCV -Absolute reticulocyte count is best -Normal/non-regenerative is less than 60,000 |
|
|
“Regenerative Response”
|
-Refers mostly to RBC regeneration
-Polychromasia is good indicator on a blood smear -Reticulocyte count is best parameter overall -Anisocytosis and macrocytosis are suggestive only -Bone marrow aspirate or core biopsy is needed in non-regenerative anemias to differentiate between aplasia, maturation defects, and infiltrative processes |
|
|
Red Cell Indices
|
-Mean Corpuscular Volume (MCV)
-Mean Corpuscular Hb concentration (MCHC) -Mean corpuscular Hemoglobin (MCH) -Red cell distribution width (indicates anisocytosis) |
|
|
Microcytosis
|
-Fe deficiency is main cause
-Occurs in Akita puppies -Can also indicate a hepatic shunt |
|
|
Normocytic Normochromic Anemia
|
-Indicates anemia of chronic disease
-Most common form of anemia -Least helpful -Initially seen with any form of anemia |
|
|
Macrocytic anemia, Normochromic or Hypochromic
|
-Mostly occurs within regenerative anemais
-Can occur with maturation arrest of RBCs --FeLV --Myelodysplasia -Folate deficiency without B12 deficiency |
|
|
Microcytic Hypochromic Anemia
|
-Fe deficiency
-Often mildly regenerative |
|
|
Causes of Anemia
|
-Any process primarily affecting the blood
-Sign that is associated with many blood and other diseases -Secondarily affects blood via other organ system failure -Blood loss -Hemolysis/RBC destruction -Impaired RBC production in bone marrow -Combination |
|
|
Blood Loss Anemia
|
-Anemia due to loss of blood
-Differentiate between acute, peracute, and chronic blood loss anemia -Can be due to spontaneous hemorrhage, induce hemorrhage, surgical bleeding, or biopsy-associated bleeding |
|
|
Peracute Blood Loss Anemia
|
-Massive blood loss
-more than 20% of blood volume within minutes to hour -Hypovolemia first, later anemia -Usually can see site of blood loss -Tachycardia, hypothermia, shock -Prolonged CRT -Weak pulses -Pale, dry mucus membranes |
|
|
Blood volume per body weight
|
-Dogs: 8-9%
-Cats: 6-8% --more prone to hypovolemia because blood volume is lower to start -Younger animals have larger blood volume |
|
|
Fluid Shock Therapy
|
-Replace lost fluids with isotonic crystalloids
--physiologic saline -Can use hypertonic saline, but rarely -Colloids can be used -Blood component therapy should be used only if needed --specific component is preferred, only if patient is deficient in O2 carrying capacity, decreasing PCV |
|
|
Treatment for Peracute Blood Loss Anemia
|
-Stop bleeding
-Shock therapy -Rapid IV fluids -Later give compatible blood components |
|
|
Acute Blood Loss Anemia
|
-Massive blood loss in hours or days
-Mild to severe anemia, low PCV and low TP --takes time to develop -Fluid shifts from extra-vascular to intra-vascular space -Hypovolemia and reduced skin elasticity -Increased erythropoiesis if there is adequate Fe -Site of bleeding is usually obvious -Hypoproteinemia results if there is external hemorrhage -Normocytic-normochromic in first 3 days -Macrocytic hypochromic regenerative anemia after 3 days -Increased WBCs due to stress -Platelets are variable |
|
|
Platelets in Acute blood loss anemia
|
-Will not be low due to blood loss
-Can be low if cause of bleeding or anemia is thrombocytopenia |
|
|
Treatment for Acute Blood Loss
|
-Prevent further bleeding
-Treat underlying cause -Rehydrate animal with fluid therapy -Give blood transfusion if Hct is less than 15-20% --2ml of blood per kg increases Hct by 1% -Oxyglobin can be given as temporary oxygen carrier |
|
|
Hypochromic microcytic Anemia
|
-Iron deficiency is most likely
-Can also be due to hepatic shunt |
|
|
Fe Deficiency Anemia
|
-Nutritional issue
-Absorption issue -Parasites/blood loss --hookworms, whipworms, fleas -Ulcers --cancer, NSAIDs |
|
|
Chronic Blood loss Anemia
|
-Parasites
-GI hemorrhage -Bleeding tumors in GI -Thrmobocytopenia or thrombocytopathia -Coagulopathies -Can have mild signs despite severe anemia --animal has compensated over time |
|
|
Characteristics of Chronic Blood loss Anemia
|
-Microcytic, hypochromic anemia
-Anisocytosis -Weakly regenerative, often very severe anemia -Low serum iron parameters -No Fe storage detectable -Erythroid bone marrow hyperplasia -Positive occult blood in feces -Fecal parasites, fleas, ticks -Thrombocytosis can be present -Leukopenia is rare |
|
|
Treatment for Chronic Blood Loss Anemia
|
-Treat underlying disease
-Supplement patient with Fe, Fe2+ only --treat for months -Use caution with fluid administration -Stored packed RBCs or whole blood can be given, depends on clinical signs and procedures --if given too quickly will overload the system |
|
|
Peracute Blood Loss Parameters
|
-Minutes to hours
-PCV is normal -CRT is increased -All other parameters normal |
|
|
Acute blood loss parameters
|
-Hours to days
-PCV is decreased -CRT is increased -Skin turgor is decreased -Reticulocytes are increased -MCV is increased -MCHC is normal or decreased -Iron is normal |
|
|
Chronic Blood Loss parameters
|
-Days to weeks
-PCV is very decreased -CRT is normal -Skin turgor is normal -Reticulocytes are increased -MCV is decreased -MCHC is decreased -Fe is decreased |
|
|
Nucleated RBCs
|
-Indicate Pb poisoning
-Also appears with vomiting, lethargy, GI issues |
|
|
Primary Hemostasis
|
-Platelets and vWF
-Vasoconstriction happens 1st, slows blood flow -Platelets adhere to vWF --very important step --vWF allows platelets to adhere to exposed collagen -Platelets aggregate |
|
|
Secondary hemostasis
|
-Coagulation and coagulation factors
-Forms stable fibrin clot or plug from fibrinogen -Well-controlled process -Followed by fibrinolysis, breakdown of fibrin |
|
|
Primary Hemostatic Disorders
|
-Thrombocytopenia
-Thrombocytopathia -von Willebrand Disease -Vasculopathies |
|
|
Secondary hemostatic Disorders
|
-Inherited coagulopathies
-Acquired coagulopathies --liver disease --rodenticides --DIC |
|
|
Local Blood Loss Anemia
|
-Usually a hemostatic issue
-Trauma -Surgery -Tumors -Parasites -GI hemorrhage |
|
|
External Blood Loss Anemia
|
-Blood gets outside of the body, end result is loss of protein and RBCs
-GI bleeding -Plasma loss -Iron deficiency |
|
|
Surface hemorrhages
|
-Petechia
-Ecchymosis -Epistaxis -Melena |
|
|
Generalized blood loss Anemia
|
-Commonly hemostatic disorders
-Thrombocytopenia -Thrombocytopathia -Coagulopathies -DIC -Vasculopathy |
|
|
Internal blood loss Anemia
|
-Blood stays in the body, can be resorbed by the body
-Cavity or tissue blood loss -No Fe lost -Slight icterus is possible |
|
|
Cavity Bleeding blood loss anemia
|
-Hematoma
-Hemothorax -Hemopericardium -Hemoperitoneum |
|
|
Hereditary bleeding disorders
|
-vWD
-Hemophilia A and B in male dogs -Some disorders are more common in specific breeds -Usually seen in young animals |
|
|
Acquired bleeding disorders
|
-Can occur at any time or any age
-Drug and toxin exposure -Infections, tick-borne diseases -Cancer -Concurrent illness in liver or kidney |
|
|
Hemorrhage in Cats
|
-Much less common than hemorrhage in dogs
-Hereditary defects: --hemophilia A and B --Vitamin K coagulopathy --thrombopathias -Acquired disorders: --trauma, surgery --liver disease --Rodenticide toxicities --Heparin, aspirin --Thrombocytopenia |
|
|
Indications for Hemostatic Testing
|
-Diagnosis
--bleeding animal or animal at risk for bleeding --Before biopsy or surgery -Monitoring --efficacy of therapy --course of disease |
|
|
Cutical Bleeding Time
|
-Used to assess overall hemostasis
-Should be less than 4 minutes -Will be abnormal with ANY hemostatic defect -Not very sensitive or painful -Not standardized, will have varied results -Anything over 4 minutes is “prolonged” |
|
|
Tube to use for coagulation testing
|
-Citrate/blue top
-Citrate binding is reversible -1:9 ratio of citrate to blood --ratio is very important |
|
|
Diagnostic testing for Coagulation
|
-Do before any treatment
-Use appropriate blood sample in required tubes and volumes -Need excellent blood collection technique |
|
|
In-clinic hemostatic tests
|
-Buccal mucosal bleeding time (primary hemostasis)
-Cutical bleeding time (overall hemostasis) -ACT -PTT -PT -Blood smear |
|
|
Activated Clotting atime
|
-Tests intrinsic and common pathways
-Same as PTT -Should clot within 100 seconds -Will be prolonged with all coagulopathies except for factor VII deficiency -Can be affected by thrombocytopenia |
|
|
Intrinsic Pathway
|
-Factors 12, 11, 9, 8
|
|
|
Extrinsic Pathway
|
-Factor 7 and tissue thomboplastin (factor III)
|
|
|
Common Pathway
|
-Factor 10, prothrombin/factor 2, fibrinogen/factor 1, factor V
|
|
|
Fibrin production
|
-Localized to injury site
-Carefully regulated -Markedly accelerated |
|
|
Factor 12
|
-Not involved in coagulation in vivo
-Activated in vitro |
|
|
ACT/PTT
|
-Tests the majority of clotting factors
-Does not test for factor VII |
|
|
Plasma activity assays for clotting
|
-Citrated plasma or citrated whole blood
-Add Ca -Activation of intrinsic or extrinsic cascade -Tests for the formation of fibrin -Measured in seconds -Abnormal when above normal range |
|
|
Clotting disorder Therapy Considerations
|
-Do not cause more harm!
--no elective surgeries, careful venipuncture -Remove dangerous agents/drugs -Stop bleeding --local hemostasis and plasma products -Correct circulatory volume if severe --crystalloid fluids for hypovolemia --NO colloids, may cause hemorrhage --RBCs in severe anemia -Give specific therapies if needed -Monitor efficacy |
|
|
Transfusion Therapy
|
-Blood type all DEA1 negative dogs
-Cats have naturally-occuring antibodies, blood type cats! -Cross-match when animal has been previously transfused |
|
|
Blood components
|
1. Fresh Whole blood: can use in all patients, but might not be needed
-Can cause reactions 2a. Packed red cells 2b. Fresh frozen plasma 3a. Cryo-poor plasma 3b. Cryoprecipitate (for hemophilia) 2c. Platelet rich plasma 3c. Platelet concentrate 3d. Fresh frozen plasma |
|
|
Hemophilia A
|
-In males only
-Develops into osteoarthrosis -Normal PT -Prolonged PTT -Decreased factor 7 activity -Normal factor 11 activity |
|
|
Hemophilia A treatment
|
-Fresh frozen plasma or cryoprecipitate
-Want to give animal factor 7 -Fresh frozen plasma and cryoprecipitate have more concentrated factor 7 -Do not give whole blood, does not have platelets or clotting factors |
|
|
Hereditary Coagulopathies
|
-Commonly seen in many breeds
-Fibrinogen: Bichon Frise, mixed breeds (PTT and PT) --FFP, cryo -Prothrombin: cocker, boxer (PTT and PT) --FFP, cryo-poor -Factor 7: beagle and others (PT) --FFP, cryo-poor -Factor 8: many breeds and cats (PTT) --cryo, FFP -Factor 9: many breeds and cats (PTT) --FFP, cryo-poor -Factor 10: cocker spaniel (PTT and PT) --FFP, cryo-poor -Factor 11: Kerry blue terrier (PTT) --FFP -Factor 12: Domestic, oriental short-haired (PTT) --None |
|
|
Vitamin K-dependent Clotting Factors
|
-2, 7, 9, 10
-Vitamin K carboxylates proteins, proteins are essential for binding Ca -Fibronigen to fibrin conversion does not involve a coagulation factor |
|
|
Vitamin K Deficiency
|
-Anti-coagulant rodenticides
--Warfarin, Indandione, bromadiolone, Brodifacoum -Coumadin therapy or toxicity -Sweet clover poisoning in cattle -GI malabsorption -Oral antibiotic therapy -Nutritional vitamin K deficiency -Hepatic diseases |
|
|
Vitamin K Deficiency Clinical Signs
|
-Clinical signs appear 2-4 days after ingestion, may last for weeks
-Hemorrhage at any traumatized site --hematoma and cavity bleeding --GI and thoracic hemorrhage -Anemia, hypovolemic shock -Lethargy, dyspnea, anorexia, vomiting -Acute death from bleeding into brain, pericardium, thorax |
|
|
Anticoagulant Rodenticide Poisoning Diagnostic tests
|
-Massive prolongation of PT and PTT
-May or may not show thrombocytopenia -Variations of acute anemia -Toxicological analysis -Low factor 2, 7, 9, 10 -Normal thrombin time |
|
|
Treatment for Anticoagulant Rodenticide poisoning
|
-Vitamin K1 and plasma
--oral, IV, or SQ vitamin K -Do not induce emesis if bleeding, rodenticide is already past stomach --can cause trauma and bleeding -Do not give vitamin K IM, can cause trauma and more bleeding |
|
|
Blood component therapy for Coagulopathies
|
-Cryo-poor plasma: best for rodenticide poisoned animals
-Fresh frozen plasma: contains all coagulation factors and is very available -Cryoprecipitate: rich in fibrinogen, factor 7, and vWF -Fresh whole blood: best for bleeding and anemic animals -Stored packed cells: ONLY if patient is anemic --does not contain any clotting factors |
|
|
Initial Rodenticide Poisoning
|
-Within hours: normal coagulation tests |
|
|
Anticoagulant effects of Aspirin
|
-Normal PT
-normal PTT -Affects platelets |
|
|
Anticoagulant effects of heparin
|
-Mild PT prolongation
-Severe PTT prolongation --largest effect on PTT |
|
|
Anticoagulant effects of Warfarin
|
-Severe PT prolongation
-Severe PTT prolongation |
|
|
Disseminated Intravascular Coagulation
DIC |
-Thrombotic and hemorrhagic syndrome associated with many diseases
-Thrombosis that turns into secondary bleeding -Neoplasia: metastatic cancer, hemangiosarcoma, leukemias -infection -Inflammation/necrosis |
|
|
Infectious causes of DIC
|
-Gram- sepsis (Leptospirosis)
-Infectious canine Hepatitis -Parvovirus -FIP -Babesiosis -Dirofilariasis |
|
|
Inflammatory causes of DIC
|
-Heat stroke
-Shock/acidosis -Burns -Snake venom -Vascular disease -GDV -Pancreatic disease -Acute hepatic disease -Hemolytic crisis -Obstetric accidents |
|
|
Factors associated with DIC
|
-endothelial damage
-endotoxemia -Circulating antigen-antibody complex -Platelet activation -Red cell damage -Tissue damage |
|
|
DIC Pathogenesis of Initial thrombotic phase
|
-Results in collagen-mediated activation of tissue thromboplastin
-Results in activation of factor 7 and thrombin formation -Circulating thrombin causes fibrin monomer formation, polymerization, and deposition -Microvascular thrombosis results --micro-thrombi are hard to find -Microvascular thrombi interfere with blood flow -Peripheral ischemia results, organ damage |
|
|
DIC pathogenesis
|
-Platelets trapped by fibrin deposits, activated to thrombocytopenia
-Activated coagulation and plasmin increase -Plasmin degrades fibrinogen and fibrin --forms FDPs -Results in hemorrhage -Kininogen system is activated by factor 12 --increased vascular permeability, hypotension, shock |
|
|
DIC pathology
|
-Most often thrombosis is seen on pathology, not hemorrhage
|
|
|
Hemostatic tests for DIC
|
-Fibrinogen
-Fibrin degradation products --D-dimers, fibrin split products, and fibrinogen degradation products -Antithrombin III will have low values -Thromboelastography |
|
|
DIC overview
|
-Thrombosis followed by hemorrhage
-Throbocytopenia, platelets are used in thrombosis -Schistocytes and nucleated RBCs indicate endothelial damage -Low fibrinogen -Low antithrombin III levels -Increased fibrin split products and fibrin degradation products -Increased D-dimers |
|
|
DIC treatment
|
-Remove trigger or treat underlying disease |
|
|
RBC lifespan
|
-Dogs: 120 days |
|
|
Solid Tumors
|
-Tumors that originate in one site
-Visible, palpable mass -May metastasize to other sites -All epithelial and mesenchymal tumors are “solid tumors” -Treatment: surgery and radiation therapy |
|
|
Clinical Behavior of a Solid tumor
|
-Can be locally invasive or not
-May or may not metastasize -Behavior varies with tumor type and grade -Prognostic factors are used to predict clinical and biological behavior of a tumor --guide treatment |
|
|
Factors to determine Chemotherapy
|
-Grade
-Stage -Specific tumor type -Tumor clinical behavior within the patient |
|
|
Tumor Grade
|
-Low, Medium, or High
-Histopthological evaluation of the tumor --NOT assigned based on cytological description -Assigned based on standardized system --number of mitotic figures --cellular pleomorphism --necrosis --vascular invasion -More of criteria present, higher the tumor grade -Predictive of metastatic potential for many solid tumors -High grade tumors have high risk of metastasis, low have low risk |
|
|
Tumor Stage
|
-Clinical assessment of primary tumor
-Determined by physical examination and diagnostic tests -Most solid tumors are staged according to WHO TNM criteria |
|
|
TNM staging System
|
T: tumor
-scored according to size and invasiveness of the primary tumor N: Lymph Node -lymph node metastasis detection M: Distant metastasis -presence or absence of detectable distant metastasis |
|
|
Tumor Staging Tests
|
-Sarcomas metastasize via blood vessels (hematogenously)
-Carcinomas metastasize via Lymphatics -CBC, Chem, Urinalysis -Regional lymph node aspirate (carcinomas) -Chest radiographs -Ultrasound -Advanced imaging (CT, MRI) |
|
|
Tumor Type
|
-Type of tumor determines whether chemotherapy is warranted
--canine osteosarcoma --hemangiosarcoma -Local therapy is usually sufficient for other tumors --cutaneous melanoma --feline osteosarcoma --hemangiopericytoma -Need to consider all factors, do not just go by what type of tumor it is |
|
|
Tumor Clinical Behavior
|
-If tumor is acting weird, chemotherapy may be warranted
--Big changes in short periods of time --necrotic, ulcerated tumor --large size --detectable metastatic disease -more aggressive treatment needed |
|
|
Hemangiosarcoma
|
-High-grade soft tissue sarcoma
-Much more common in dogs compared to cats -Primary locations: --spleen --liver --heart --SQ tissue -Fast growing and highly metastatic, intra-abdominal and pulmonary metastasis |
|
|
Hemangiosarcoma Staging
|
-Stage according to size of tumor and whether it has ruptured
-Stage 1: less than 5cm diameter, non-ruptured solitary tumor -Stage 2: Tumor greater than 5cm, or ruptured solitary tumor -Stage 3: Metastasis -Base staging results based on CBC/CS/UA, chest radiographs, abdominal ultrasound |
|
|
Hemangiosarcoma Treatment
|
-Surgical resection
-Chemotherapy -No surgery option, can do palliative care --chemotherapy --radiation therapy --supportive care |
|
|
Hemangiosarcoma Prognosis
|
-Poor, mostly die of metstatic disease
-Stage 1: 8-10 months -Stage 2: 6-7 months -Stage 3: 3-4 months -Depends on location and initial severity |
|
|
Chemotherapy for Solid Tumors
|
-Adjuvant
-Neo-adjuvant -Palliative |
|
|
Adjuvant chemotherapy
|
-Administered in microscopic disease setting
-Delays or prevents metastatic disease -Recommended after local therapy for high-grade tumors -Smaller tumor burden, more effective chemotherapy will be --start soon after surgery! 10-14 days post-surgery |
|
|
Neo-Adjuvant Chemotherapy
|
-Chemotherapy that is administered in bulky disease setting before local therapy
-Decrease tumor size and make local therapy more feasible -Canine mast cell tumors -Hemangiosarcoma -Feline injection site sarcomas -Number of doses depends on tumor response -Timing of doses is important so that mass is removed before it becomes resistant to chemotherapy and has a chance to regrow --time surgery to happen when the tumor is at its smallest |
|
|
Advantages of Neoadjuvant Chemotherapy
|
-Smaller surgery site
-Smaller radiation therapy field -Helps with chemotherapy drug selection |
|
|
Disadvantages of Neoadjuvant Chemotherapy
|
-Tumor could get larger if it is growing quickly and does not respond to treatment
-Chemotherapy side effects --neutropenia, delay in surgery |
|
|
Palliative Chemotherapy
|
-Administered in bulky disease setting
-Alleviate pain or clinical signs from tumor -Goal is to extend patient’s quality of life --not long-term control of the tumor -Number of doses depends on tumor response and patient tolerance |
|
|
Osteosarcoma
|
-High grade sarcoma
-Most common primary bone tumor in dogs -Appendicular location is more common than axial locations -Present for lameness -Monostotic aggressive bone lesion on radiographs --usually affects just one bone |
|
|
Osteosarcoma staging
|
-CBC/CS/UA
-Elevated ALP negative prognostic factor -Radiographs of lungs and other bones for metastasis --chest radiographs |
|
|
Osteosarcoma Treatment
|
-Amputation of affected limb
-Chemotherapy -Combination of amputation and chemotherapy -Limb-sparing surgery -Palliative radiation therapy -Palliative medical management (analgesics and anti-inflammatories) |
|
|
Osteosarcoma Prognosis
|
-Poor
-Amputation and chemotherapy gives about a year -Palliative options or one therapy gives about 4 months |
|
|
Intracavity Chemotherapy
|
-Chemotherapy directly into the body cavity
--dilute the drug so there is adequate fluid for contact -Good to avoid carcinomatosis or mesothelioma and resulting effusion -Systemic absorption still occurs --GI and bone marrow toxicity -Penetration 1-3mm deep -Useful for palliation of effusions, unlikely to decrease size of actual tumors |
|
|
Cisplatin for Intracavity Chemotherapy
|
-Effusion resolved in 5/6 dogs with carcinomatosis or mesothelioma
-Minimal toxicity -Extensive saline diuresis |
|
|
Carboplatin and Mitoxantrone Intracavity Chemotherapy
|
-Lengthens survival time
|
|
|
Pleuroports
|
-SQ ports that are surgically placed into thoracic cavity
-Make fluid drainage and chemotherapy administration easier -Depending on owner, fluid drainage can be performed at home |
|
|
“Localized” Chemotherapy
|
-Intra-arterial: chemotherapy injected into the arterial blood supply to the tumor
-Intra-lesional: chemotherapy injected directly into a tumor --Chemotherapy injected into surgery site of soft-tissue sarcoma or osteosarcoma resection |
|
|
Targeted Chemotherapy
|
-Palladia, Kinavet |
|
|
Hemolytic Anemias
|
-Accelerated RBC destruction
-Intravascular, extravascular -Intrinsic (RBC itself is damaged) -Extrinsic (external things are damaging RBC) -Inherited or acquired -Compensated or uncompensated -All are regenerative anemais except during the first few days -No bone marrow disorder or iron deficiency, just RBC destruction |
|
|
RBC Destruction
|
-Normal pathway and process AND pathological process
-Macrophages phagocytose old or diseased RBCs in the spleen -RBCs are broken down into components --Fe, Globin, Billirubin --Fe goes into tissues for storage --Globin is recycled -Bilirubin is put into the bloodstream --increased bilirubinemia/bilirubinuria is hallmark of hemolysis |
|
|
Extravascular Hemolysis
|
-RBCs are phagocytosed by macrophages
-RBCs are broken down into components (Fe, Globin, Bilirubin) -Unconjugated bilirubin is sent to Liver for conjugation |
|
|
Intravascular Hemolysis
|
-More dramatic process, less common
-RBCs are damaged and lysed within the vasculature -Haptoglobin binds free Hb and brings Hb to the liver --has limited capacity, is easily overwhelmed --results in free Hb in the vasculature -Can see Hb in plasma, will turn pink -Free Hb does not cause damage to kidneys in dogs and cats |
|
|
Pathophysiology of Hemolytic Anemias
|
-Hereditary RBC defects
-Immune-mediated hemolytic Anemia -Hemolysis associated with infection -Hemolysis associated with chemicals or mechanical breakdown |
|
|
Clinical Signs of Hemolysis
|
-Anemia
-Pigmenturia -Icterus --may not see icterus, body may have developed enhanced metabolism of RBCs -Splenomegaly -Fever -Cyanosis (rare) |
|
|
Laboratory tests for Hemolysis
|
-Hyperbilirubinemia
-Bilirubinuria -Hemoglobinemia (intravascular) -Hemoglobinuria (intravascular) |
|
|
Poikilocytosis
|
-RBCs of abnormal shapes and sizes
-Can indicate hemolysis |
|
|
RBC membrane defects
|
-Abnormally formed RBCs
-Abnormal RBC shape -Increased osmotic fragility -Deficient RBC membrane protesin |
|
|
Feline Porphyrias
|
-Dominant and recessive forms
-Mild to severe anemia and pigmenturia -Discoloration or fluorescent teeth and bones --porphyrins are deposited in the teeth |
|
|
Pyruvate Kinase Deficiency
|
-Can cause intermittent severe hemolytic crises
-Exaggerated by infections and other illnesses -Regenerative mild to severe anemia -Mild splenomegaly -Causes osteosclerosis in animals over 1 year old -Mutations are breed-specific |
|
|
Phosphofructokinase deficiency
|
-Intermittent severe hemolytic anemia and intermittent icterus
-Metabolic myopathy, muscle cramping -Induced by heat, exercise, or barking -Causes intravascular and extravascular hemolysis |
|
|
Hereditary RBC defects
|
-Hemoglobinopathies
--not described in dogs and cats -Cytosolic enzyme deficiencies --Pyruvate kinase deficiency --phosphofructokinase deficiency -Membrane abnormalities --Elliptocytosis --Stomatocytosis --Spherocytosis --Increased osmotic fragility |
|
|
Primary Immune-mediated Hemolytic Anemia
|
-Autoimmune issue
-Idiopathic -Issue is with the animal itself |
|
|
Secondary Immune-mediated Hemolytic Anemia
|
-Known causes
-Some agent on the RBC membrane is causing immunological reaction |
|
|
Genetic Predisposition for IMHA
|
-Breed predilection for cocker spaniels
--33% of all cases -Poodles, Old English Sheep dogs, English springer spaniels, dachshunds also |
|
|
Infectious diseases and IMHA
|
-Lots of infectious agents, can cause RBC destruction
-Babesiosis -Ehrlichiosis -Leishmaniasis -Dirofilariasis -Bacterial infections --Leptospirosis, chronic abscesses, discospondylities, pyometra, colitis, pyelonephritis |
|
|
IMHA and vaccinations
|
-Vaccines can trigger an underlying condition that stimulates immune system
-Macrophages are stimulated and take out Ab-marked RBCs -25% of IMHA cases occur within 1 month of vaccination |
|
|
Seasonality of IMHA
|
-IMHA cases are higher in summer months
-Warmer months, more infections and antigens around -Suggests trigger --infection, inflammation, allergy, other |
|
|
IMHA in dogs
|
-Causes massive inflammatory an necrotic processes
-HUGE neutrophil response -Will have leukocytosis with or without a left shift -High plasma fibrinogen levels -Variably increased liver enzyme levels -Evidence of infection is common -Clumped red cells, spherocytes, positive coomb’s test, persistent agglutination |
|
|
IMHA diagnosis
|
-Search for underlying diseases and triggers
--genetics --infection --inflammation and necrosis -Drugs, chemicals, insect stings -Neoplasia |
|
|
Diagnosis of Autoimmune Hemolytic Anemia
|
-Diagnosis of exclusion
-Rule out all other possible causes |
|
|
Clinical Evidence of Immune Destruction
|
1. Presence of Hemolysis
-Extravascular: hyperbilirubinuria and icterus -Intravascular: Hemoglobinurua, icterus 2. Regenerative Bone marrow Response -polychromasia, reticulocytosis 3. Immune destruction -autoagglutination, spherocytes, positive coombs’ test 4. Additional tests --platelet antibodies --positive ANA --test for hypothyroidism |
|
|
Autoagglutination
|
-Can be macroscopic or microscopic
-Saline agglutination is NOT a sufficient test --breaks up rouleaux but not other forms of agglutination -True or persistent agglutination is done by mixing 1:4 blood to saline --spin sample, remove supernatant --repeat 3 times, check for agglutination -With persistent autoagglutination cannot do any blood testing, blood agglutinates! |
|
|
Spherocytosis
|
-Indication of immune destruction of RBCs
--any dog with 20-30% spherocytes probably has IMHA -Partially phagocytosed or lysed RBCs -Macrophages chop off a small segment of RBC membrane -Marker phagocytosis is strongly suggestive of IMHA --can also be seen with poor formation of RBCs -Spherocytes are rarely seen with other diseases besides IMHA --usually in small amounts --zinc toxicosis, DIC, sepsis |
|
|
Direct Coombs’ Test
|
-Tests for presence of antibodies on RBCs
-Allo and auto antibodies on the RBC surface -Can do as a strip or as a capillary test |
|
|
Positive Coomb’s test
|
-Direct coomb’s or antiglobulin test
-Detects IgG, IgM and complement on RBCs -Species specific reagents -Needs to be done in an established lab -Measures agglutination -If true agglutination happens, cannot do test |
|
|
IMHA prognosis
|
-High mortality rate, even with major supportive therapy
--30% -Death due to anemia and complications -Most deaths occur in the first few weeks of disease -No conservative or aggressive therapy has been better than any others -VERY difficult disease to treat |
|
|
Fluid therapy for Anemia
|
-Rehydration and maintenance of hydration is essential!
-Needed to avoid hypoxia and thrombosis, even if it lowers PCV overall |
|
|
Blood Transfusions with IMHA
|
-Transfusions are beneficial for IMHA patients
-Want freshest RBCs available -Provide blood type and cross-match compatible blood -If there is true autoagglutination and unknown blood type, only give DEA 1.1- blood |
|
|
Therapeutic treatment for IMHA
|
-Treat underlying disease or remove trigger first!
-Impair phagocytosis, reduce clearance of Ab coated RBCs -Decrease complement activation -Reduce anti-RBC antibody production -Limit adverse effects of immunosuppressive therapy |
|
|
Adverse effects of Immunosuppressive therapy for IMHA
|
-Bone marrow suppression
--can lead to cytopenias -Predisposes patient to infection -Predisposes patient to thrombosis -Lots of other side effects |
|
|
Glucocorticoids for IMHA treatment
|
-Preferred initial treatment
-Impair expression and function of macrophage Fc receptors -Immediately effective -Prednisolone or Dexamethasone -Major side effects are expected --PU/PD, immunodeficiency, leukocytosis, neutrophilia, weakness, thin skin, hair loss -Does NOT decrease Ab expression on RBC surface |
|
|
IMHA glucocorticoid treatment duration
|
-Varies by individual
-Could be 1-3 months, or as long as 6 months -Look at immunological parameters to determine end of treatment --spherocytes, autoagglutination, Coombs’ test |
|
|
Immunosuppressive Agents for IMHA treatment
|
-Glucocorticoids
-Azathioprine -Cyclosporine -Cyclophosphamide -Danazol -Leflunamide -Mycophenylate -Human Ig |
|
|
Splenectomy for IMHA treatment
|
-Rarely done
-Has not been adequately investigated -May be warranted therapeutically and diagnostically if spleen is large or irregular and there is no response to other treatments -Post-splenectomized dogs are severely immunocompromised, need to be monitored |
|
|
Fe supplementation for IMHA
|
-Not necessary!
-RBCs are lysed in the body, Fe is bioavailable and recirculated --does not need to be supplemented -Can accumulate excess Fe in the liver, will lead to hepatic failure |
|
|
Hemolysis and Alloantibodies
|
-Previously transfused dogs or type B cats have alloantibodies to RBCs
-Transfusion without a cross-match will result in reaction |
|
|
Feline Neonatal isoerythrolysis
|
-Type A or AB kittens born to type B queens
-Type B queen has alloantibodies to all other RBCs -when kittens drink colostrum, ingest Ab, and will attack own RBCs -Kittens have massive hemoglobinuria due to intravascular hemolysis -Get ill after nursing -May suddenly die during the 1st day |
|
|
Prevention of Neonatal Isoerythrolysis
|
-Only breed type B queens t B toms
-Do not allow type A kittens to nurse from B queens -Foster nurse kittens with milk replacer for 24 hours |
|
|
Transfusion reactions in Cats
|
-Type B cat receiving type A blood
-Due to anti-A antibodies in B patient plasma -Less than 1ml of blood can be fatal! -Causes hypotension, bradycardia, tachycardia, shock -Hemoglobinuria, hyperthermia, hypothermia |
|
|
Babesia Canis
|
-Most likely infectious agent that can cause hemolytic anemia in dogs
|
|
|
Mycoplasma hemofelis
|
-Most likely infectious agent to cause hemolytic anemia in cats
|
|
|
Feline Hemobartonellosis
|
-Hemomycoplasma with several distinct species
-Mycoplasma felis: large and more pathogenic -Mycoplasma hemominutum: small form -Mycoplasma turicensis: small form -Diagnose on blood smear and PCR --cannot do serology for Dx -Transmission is unknown -Infection causes RBC distortion --sequestration and removal of RBCs by spleen --increased osmotic fragility, immune hemolysis -Cyclic or progressive hemolytic anemia and fever -Recovered cats are chronic carrier |
|
|
Feline Mycoplasma felis Treatment
|
-Doxycycline
-Prednisolone -Transfusions |
|
|
Canine Babesiosis
|
-Several hemoprotozoans in North America
-Babesia canis is large, bi-lober, piriform, often paired -babesia gibsoni is smaller, singular -Babesia comrade in California -Many infected dogs are subclinical carriers -Babesia multiplies in RBCs via budding |
|
|
Canine Babesiosis Diagnosis
|
-Blood smear with pear-shaped organisms in RBCs
-indirect fluorescent antibody test -B. canis and B gibsoni antibodies will cross-react --need to do PCR to differentiate |
|
|
Canine Babesiosis Clinical signs
|
-Regenerative anemia
-Thrombocytopenia -Hyperbilirubinuria -Fever -DIC leading to death |
|
|
Treatment for Babesia
|
-Imidocarb diproprionate
--effective for B. canis, not so much for B gibsoni -Diminazene -Clindamycin -Metronidazole -Prednisone with severe hemolysis -Blood transfusions -Remove the tick vector |
|
|
Hemolytic Anemias associated with Infections
|
-Hemobartonellosis in cats and dogs
-Babesiosis in dogs -Cytauxzoonosis in cats -Ehrlichiosis in dogs -Caval syndrome -Leptospirosis -Sepsis |
|
|
Zinc Intoxication
|
-Gastric foreign body
-Increases plasma zinc levels -Causes intravascular hemolysis -GI signs usually present -Endoscopic removal or surgery for treatment -Transfusions can be helpful |
|
|
Heinz Bodies
|
-Precipitated Hemoglobin
-Refractile bodies on a regular stain -Distort RBCs and cause hemolysis -Small buds on the edges of RBC membranes |
|
|
Heinz Body Anemia
|
-Precipitated Hb, cannot bind to O2
-History of exposure to drugs or onions -Lthargy, weakness, anorexia, vomiting, salivation, death -Causes pallor or icterus -Hemoglobinuria -Bilirubinuria |
|
|
Methemoglobinemia
|
-Oxidized hemoglobin
-Does not bind O2 -Can be caused by many chemicals --acetaminophen in cats -Onions, broccoli -Blood is not oxygenated, causes cyanosis |
|
|
Methemoglobinemia Clinical Signs
|
-Lethargy, weaknes
-Anorexia, vomiting -Salivation -Death -Cyanosis -Tachypnea and tachycardia |
|
|
Toxic Hemolytic anemias
|
-Heinz body anemia: precipitated Hb
-Methemoglobinemia: oxidized heme, prevents O2 binding -Intravascular hemolysis: results in hemoglobinemia and hemoglobinuria |
|
|
Treatment for Toxic Hemolysis
|
-Remove offending agent
--may need surgery to remove foreign body -Induce emesis if early enough -Activated charcoal and cathartics -Acetylcysteine (Mucomyst) -Methylene Blue -Ascorbic acid -Sodium sulfate -Blood transfusions and other supportive care |
|
|
Hypophosphatemia and Hemolytic Anemia
|
-Decrease in serum phosphate results in decreased ATP availability
-Decrease in phosphate is due to treatment of hepatic lipidosis or diabetes mellitus, shift of phosphate into the tissues --more phosphate is lost from kidneys, decreased absorption from GI -Results in Heinz body formation and hemolytic anemia -Give oral or IV phosphate |
|
|
Microangiopathic Hemolytic Anemia Lab signs
|
-Schistocytes in peripheral blood smears
-Fragmented RBCs -Part of DIC classic signs -Platelets are usually decreased -Abnormal coagulation tests -FSP and D-dimers increased |
|
|
Microangiopathic Hemolytic Anemia Causes
|
-Vasculitis |
|
|
Pathophysiology of Hemolytic Anemias |
-ignore |
|
|
Hemolytic Anemias |
-Accelerated RBC destruction
-Intravascular, extravascular -Intrinsic (RBC itself is damaged) -Extrinsic (external things are damaging RBC) -Inherited or acquired -Compensated or uncompensated -All are regenerative anemais except during the first few days -No bone marrow disorder or iron deficiency, just RBC destruction |
|
|
RBC Destruction |
-Normal pathway and process AND pathological process
-Macrophages phagocytose old or diseased RBCs in the spleen -RBCs are broken down into components --Fe, Globin, Billirubin --Fe goes into tissues for storage --Globin is recycled -Bilirubin is put into the bloodstream --increased bilirubinemia/bilirubinuria is hallmark of hemolysis |
|
|
Extravascular Hemolysis
|
-RBCs are phagocytosed by macrophages
-RBCs are broken down into components (Fe, Globin, Bilirubin) -Unconjugated bilirubin is sent to Liver for conjugation |
|
|
Intravascular Hemolysis
|
-More dramatic process, less common
-RBCs are damaged and lysed within the vasculature -Haptoglobin binds free Hb and brings Hb to the liver --has limited capacity, is easily overwhelmed --results in free Hb in the vasculature -Can see Hb in plasma, will turn pink -Free Hb does not cause damage to kidneys in dogs and cats |
|
|
Pathophysiology of Hemolytic Anemias
|
-Hereditary RBC defects
-Immune-mediated hemolytic Anemia -Hemolysis associated with infection -Hemolysis associated with chemicals or mechanical breakdown |
|
|
Clinical Signs of Hemolysis
|
-Anemia
-Pigmenturia -Icterus --may not see icterus, body may have developed enhanced metabolism of RBCs -Splenomegaly -Fever -Cyanosis (rare) |
|
|
Laboratory tests for Hemolysis
|
-Hyperbilirubinemia
-Bilirubinuria -Hemoglobinemia (intravascular) -Hemoglobinuria (intravascular) |
|
|
Poikilocytosis
|
-RBCs of abnormal shapes and sizes
-Can indicate hemolysis |
|
|
RBC membrane defects
|
-Abnormally formed RBCs
-Abnormal RBC shape -Increased osmotic fragility -Deficient RBC membrane protesin |
|
|
Feline Porphyrias
|
-Dominant and recessive forms
-Mild to severe anemia and pigmenturia -Discoloration or fluorescent teeth and bones --porphyrins are deposited in the teeth |
|
|
Pyruvate Kinase Deficiency
|
-Can cause intermittent severe hemolytic crises
-Exaggerated by infections and other illnesses -Regenerative mild to severe anemia -Mild splenomegaly -Causes osteosclerosis in animals over 1 year old -Mutations are breed-specific |
|
|
Phosphofructokinase deficiency
|
-Intermittent severe hemolytic anemia and intermittent icterus
-Metabolic myopathy, muscle cramping -Induced by heat, exercise, or barking -Causes intravascular and extravascular hemolysis |
|
|
Hereditary RBC defects
|
-Hemoglobinopathies
--not described in dogs and cats -Cytosolic enzyme deficiencies --Pyruvate kinase deficiency --phosphofructokinase deficiency -Membrane abnormalities --Elliptocytosis --Stomatocytosis --Spherocytosis --Increased osmotic fragility |
|
|
Primary Immune-mediated Hemolytic Anemia
|
-Autoimmune issue
-Idiopathic -Issue is with the animal itself |
|
|
Secondary Immune-mediated Hemolytic Anemia
|
-Known causes
-Some agent on the RBC membrane is causing immunological reaction |
|
|
Genetic Predisposition for IMHA
|
-Breed predilection for cocker spaniels
--33% of all cases -Poodles, Old English Sheep dogs, English springer spaniels, dachshunds also |
|
|
Infectious diseases and IMHA
|
-Lots of infectious agents, can cause RBC destruction
-Babesiosis -Ehrlichiosis -Leishmaniasis -Dirofilariasis -Bacterial infections --Leptospirosis, chronic abscesses, discospondylities, pyometra, colitis, pyelonephritis |
|
|
IMHA and vaccinations
|
-Vaccines can trigger an underlying condition that stimulates immune system
-Macrophages are stimulated and take out Ab-marked RBCs -25% of IMHA cases occur within 1 month of vaccination |
|
|
Seasonality of IMHA
|
-IMHA cases are higher in summer months
-Warmer months, more infections and antigens around -Suggests trigger --infection, inflammation, allergy, other |
|
|
IMHA in dogs
|
-Causes massive inflammatory an necrotic processes
-HUGE neutrophil response -Will have leukocytosis with or without a left shift -High plasma fibrinogen levels -Variably increased liver enzyme levels -Evidence of infection is common -Clumped red cells, spherocytes, positive coomb’s test, persistent agglutination |
|
|
IMHA diagnosis
|
-Search for underlying diseases and triggers
--genetics --infection --inflammation and necrosis -Drugs, chemicals, insect stings -Neoplasia |
|
|
Diagnosis of Autoimmune Hemolytic Anemia
|
-Diagnosis of exclusion
-Rule out all other possible causes |
|
|
Clinical Evidence of Immune Destruction
|
1. Presence of Hemolysis
-Extravascular: hyperbilirubinuria and icterus -Intravascular: Hemoglobinurua, icterus 2. Regenerative Bone marrow Response -polychromasia, reticulocytosis 3. Immune destruction -autoagglutination, spherocytes, positive coombs’ test 4. Additional tests --platelet antibodies --positive ANA --test for hypothyroidism |
|
|
Autoagglutination
|
-Can be macroscopic or microscopic
-Saline agglutination is NOT a sufficient test --breaks up rouleaux but not other forms of agglutination -True or persistent agglutination is done by mixing 1:4 blood to saline --spin sample, remove supernatant --repeat 3 times, check for agglutination -With persistent autoagglutination cannot do any blood testing, blood agglutinates! |
|
|
Spherocytosis
|
-Indication of immune destruction of RBCs
--any dog with 20-30% spherocytes probably has IMHA -Partially phagocytosed or lysed RBCs -Macrophages chop off a small segment of RBC membrane -Marker phagocytosis is strongly suggestive of IMHA --can also be seen with poor formation of RBCs -Spherocytes are rarely seen with other diseases besides IMHA --usually in small amounts --zinc toxicosis, DIC, sepsis |
|
|
Direct Coombs’ Test
|
-Tests for presence of antibodies on RBCs
-Allo and auto antibodies on the RBC surface -Can do as a strip or as a capillary test |
|
|
Positive Coomb’s test
|
-Direct coomb’s or antiglobulin test
-Detects IgG, IgM and complement on RBCs -Species specific reagents -Needs to be done in an established lab -Measures agglutination -If true agglutination happens, cannot do test |
|
|
IMHA prognosis
|
-High mortality rate, even with major supportive therapy
--30% -Death due to anemia and complications -Most deaths occur in the first few weeks of disease -No conservative or aggressive therapy has been better than any others -VERY difficult disease to treat |
|
|
Fluid therapy for Anemia
|
-Rehydration and maintenance of hydration is essential!
-Needed to avoid hypoxia and thrombosis, even if it lowers PCV overall |
|
|
Blood Transfusions with IMHA
|
-Transfusions are beneficial for IMHA patients
-Want freshest RBCs available -Provide blood type and cross-match compatible blood -If there is true autoagglutination and unknown blood type, only give DEA 1.1- blood |
|
|
Therapeutic treatment for IMHA
|
-Treat underlying disease or remove trigger first!
-Impair phagocytosis, reduce clearance of Ab coated RBCs -Decrease complement activation -Reduce anti-RBC antibody production -Limit adverse effects of immunosuppressive therapy |
|
|
Adverse effects of Immunosuppressive therapy for IMHA
|
-Bone marrow suppression
--can lead to cytopenias -Predisposes patient to infection -Predisposes patient to thrombosis -Lots of other side effects |
|
|
Glucocorticoids for IMHA treatment
|
-Preferred initial treatment
-Impair expression and function of macrophage Fc receptors -Immediately effective -Prednisolone or Dexamethasone -Major side effects are expected --PU/PD, immunodeficiency, leukocytosis, neutrophilia, weakness, thin skin, hair loss -Does NOT decrease Ab expression on RBC surface |
|
|
IMHA glucocorticoid treatment duration
|
-Varies by individual
-Could be 1-3 months, or as long as 6 months -Look at immunological parameters to determine end of treatment --spherocytes, autoagglutination, Coombs’ test |
|
|
Immunosuppressive Agents for IMHA treatment
|
-Glucocorticoids
-Azathioprine -Cyclosporine -Cyclophosphamide -Danazol -Leflunamide -Mycophenylate -Human Ig |
|
|
Splenectomy for IMHA treatment
|
-Rarely done
-Has not been adequately investigated -May be warranted therapeutically and diagnostically if spleen is large or irregular and there is no response to other treatments -Post-splenectomized dogs are severely immunocompromised, need to be monitored |
|
|
Fe supplementation for IMHA
|
-Not necessary!
-RBCs are lysed in the body, Fe is bioavailable and recirculated --does not need to be supplemented -Can accumulate excess Fe in the liver, will lead to hepatic failure |
|
|
Hemolysis and Alloantibodies
|
-Previously transfused dogs or type B cats have alloantibodies to RBCs
-Transfusion without a cross-match will result in reaction |
|
|
Feline Neonatal isoerythrolysis
|
-Type A or AB kittens born to type B queens
-Type B queen has alloantibodies to all other RBCs -when kittens drink colostrum, ingest Ab, and will attack own RBCs -Kittens have massive hemoglobinuria due to intravascular hemolysis -Get ill after nursing -May suddenly die during the 1st day |
|
|
Prevention of Neonatal Isoerythrolysis
|
-Only breed type B queens t B toms
-Do not allow type A kittens to nurse from B queens -Foster nurse kittens with milk replacer for 24 hours |
|
|
Transfusion reactions in Cats
|
-Type B cat receiving type A blood
-Due to anti-A antibodies in B patient plasma -Less than 1ml of blood can be fatal! -Causes hypotension, bradycardia, tachycardia, shock -Hemoglobinuria, hyperthermia, hypothermia |
|
|
Babesia Canis
|
-Most likely infectious agent that can cause hemolytic anemia in dogs
|
|
|
Mycoplasma hemofelis
|
-Most likely infectious agent to cause hemolytic anemia in cats
|
|
|
Feline Hemobartonellosis
|
-Hemomycoplasma with several distinct species
-Mycoplasma felis: large and more pathogenic -Mycoplasma hemominutum: small form -Mycoplasma turicensis: small form -Diagnose on blood smear and PCR --cannot do serology for Dx -Transmission is unknown -Infection causes RBC distortion --sequestration and removal of RBCs by spleen --increased osmotic fragility, immune hemolysis -Cyclic or progressive hemolytic anemia and fever -Recovered cats are chronic carrier |
|
|
Feline Mycoplasma felis Treatment
|
-Doxycycline
-Prednisolone -Transfusions |
|
|
Canine Babesiosis
|
-Several hemoprotozoans in North America
-Babesia canis is large, bi-lober, piriform, often paired -babesia gibsoni is smaller, singular -Babesia comrade in California -Many infected dogs are subclinical carriers -Babesia multiplies in RBCs via budding |
|
|
Canine Babesiosis Diagnosis
|
-Blood smear with pear-shaped organisms in RBCs
-indirect fluorescent antibody test -B. canis and B gibsoni antibodies will cross-react --need to do PCR to differentiate |
|
|
Canine Babesiosis Clinical signs
|
-Regenerative anemia
-Thrombocytopenia -Hyperbilirubinuria -Fever -DIC leading to death |
|
|
Treatment for Babesia
|
-Imidocarb diproprionate |
|
|
Hemolytic Anemias associated with Infections
|
-Hemobartonellosis in cats and dogs
-Babesiosis in dogs -Cytauxzoonosis in cats -Ehrlichiosis in dogs -Caval syndrome -Leptospirosis -Sepsis |
|
|
Zinc Intoxication
|
-Gastric foreign body
-Increases plasma zinc levels -Causes intravascular hemolysis -GI signs usually present -Endoscopic removal or surgery for treatment -Transfusions can be helpful |
|
|
Heinz Bodies
|
-Precipitated Hemoglobin
-Refractile bodies on a regular stain -Distort RBCs and cause hemolysis -Small buds on the edges of RBC membranes |
|
|
Heinz Body Anemia
|
-Precipitated Hb, cannot bind to O2
-History of exposure to drugs or onions -Lthargy, weakness, anorexia, vomiting, salivation, death -Causes pallor or icterus -Hemoglobinuria -Bilirubinuria |
|
|
Methemoglobinemia
|
-Oxidized hemoglobin
-Does not bind O2 -Can be caused by many chemicals --acetaminophen in cats -Onions, broccoli -Blood is not oxygenated, causes cyanosis |
|
|
Methemoglobinemia Clinical Signs
|
-Lethargy, weaknes
-Anorexia, vomiting -Salivation -Death -Cyanosis -Tachypnea and tachycardia |
|
|
Toxic Hemolytic anemias
|
-Heinz body anemia: precipitated Hb
-Methemoglobinemia: oxidized heme, prevents O2 binding -Intravascular hemolysis: results in hemoglobinemia and hemoglobinuria |
|
|
Treatment for Toxic Hemolysis
|
-Remove offending agent
--may need surgery to remove foreign body -Induce emesis if early enough -Activated charcoal and cathartics -Acetylcysteine (Mucomyst) -Methylene Blue -Ascorbic acid -Sodium sulfate -Blood transfusions and other supportive care |
|
|
Hypophosphatemia and Hemolytic Anemia
|
-Decrease in serum phosphate results in decreased ATP availability
-Decrease in phosphate is due to treatment of hepatic lipidosis or diabetes mellitus, shift of phosphate into the tissues --more phosphate is lost from kidneys, decreased absorption from GI -Results in Heinz body formation and hemolytic anemia -Give oral or IV phosphate |
|
|
Microangiopathic Hemolytic Anemia Lab signs
|
-Schistocytes in peripheral blood smears
-Fragmented RBCs -Part of DIC classic signs -Platelets are usually decreased -Abnormal coagulation tests -FSP and D-dimers increased |
|
|
Microangiopathic Hemolytic Anemia Causes
|
-Vasculitis
-Dirofilariasis/caval syndrome -Hemangiosarcoma or metastatic tumors -Severe hepatic disease -Snake bites |
|
|
Pathophysiology of Hemolytic Anemias
|
-Hereditary RBC deficiencies
-Immune-mediated hemolytic anemia -Hemolysis associated with infection -Hemolysis associated with chemicals |
|
|
Non-regenerative Anemia
|
-Occurs during first few days of ANY anemia
-Usually normocytic, normochromic -Sometimes associated with leukopenia or thrombocytopenia --Bone marrow is only site with RBCs, WBCs, and platelet production |
|
|
Bone marrow exam for Hematopoiesis
|
-Important to find Non-regenerative anemia
-Normal cellularity should be 40-70% -Aspirate is generally preferred over a core biopsy -Myeloid to RBC ratio should be 1.25 in dogs and 1.6 in cats -Should see maturation of all hematopoietic lines -Fe staining with Prussian blue -Should see lymphocytes, plasma cells, tumor cells |
|
|
Types of non-regenerative anemia
|
-Refractory anemia
-Aplastic anemia |
|
|
Refractory Anemia
|
-non-regenerative anemia in which Leukocytes and platelets are spared
-Disease is outside of the bone marrow -No panleukopenia present -Anemia of chronic disease -Fe deficiency anemia -Chronic renal failure -Other organ disorders |
|
|
Aplastic Anemia
|
-Non-regenerative anemia with pancytopenia
-Bone marrow disease --aplastic or hypoplastic bone marrow -Can be due to chemicals or radiation exposure -Infection (ehrlichiosis) -leukemia and other neoplasia, tumor replaces bone marrow tissue |
|
|
Myelodysplastic syndrome
|
-Group of related bone marrow disorders
-Cytopenias -Normal or hypocellular bone marrow -Dyspoiesis with relative excess of blast cells -May progress to overt leukopenia, can result in cancer |
|
|
Nutritional deficiency Anemia
|
-Fe deficiency
-Vitamin deficiency (B12 or folate) -GI malabsorption |
|
|
Chemical-induced aplastic anemia
|
-Estrogen
-Phenylbutazone -Chemotherapeutic agents -Irradiation -Idiopathic |
|
|
Estrogen-induced Aplastic Anemia
|
-Can be due to a cryptorchid retained testicle
-Affects bone marrow of dogs and ferrets -Endogenous or exogenous estrogen source -Estrogens regulate stem cell proliferation, block EPO utilization --does not block EPO secretion -Other bone marrow cell lines are stimulated to exhaustion -Dogs may be more sensitive due to decreased affinity of plasma proteins to bind estrogens |
|
|
Endogenous estrogen inducing anemia
|
-Sertoli cell tumor
-Seminoma -Interstitial and granulosa cell tumors -Ferrets with prolonged estrus |
|
|
Exogenous estrogen inducing anemia
|
-Therapeutic estrogen administration
-Oral diethylstilbesterol |
|
|
Bone marrow suppression with Estrogen induced anemia
|
-Severe bone marrow suppression occurs within weeks
-Toxicity is often irreversible -Pancytopenia has a poor prognosis -Increased serum estrogens |
|
|
Clinical signs of Estrogen induced anemia
|
-Clinical signs depend on cause of estrogen excess
-Result from cytopenias and feminization -Anemia -Hemorrhage due to thrombocytopenia -Infection -Abdominal mass -Hair loss |
|
|
Treatment for Estrogen induced Anemia
|
-Remove endogenous or exogenous estrogen source
-Fresh blood transfusions -Antibiotics -Females respond better than males -Generally poor prognosis -Prevention is most important! --do not use any high-dose estrogens in dogs! |
|
|
Anemia of chronic disease
|
-Most common form of non-regenerative anemia
-Occurs with all other organ diseases --chronic infections, inflammation, neoplasia -Fe sequestration by macrophages causes shorter RBC lifespan -RBCs are sequestered -Causes a mild to moderate anemia |
|
|
Lab findings with Anemia of chronic disease
|
-non-regenerative
-Normocytic, normochromic anemia -Decreased serum Fe, decreased Fe binding capacity -Will have adequate Fe stores in bone marrow, just no Fe in circulation -Hypoplastic or normal bone marrow -Increased macrophages and Fe in bone marrow -DDx: iron deficiency |
|
|
Anemia of Chronic Disease Treatment
|
-Treat underlying disease
-Otherwise no specific therapy -Fe supplementation is not helpful, animal is not Fe deficient |
|
|
Pure Red Cell Aplasia
|
-No red cell precursors are available
-Selective erythroid bone marrow depression results in anemia -may be immune-mediated -Clinical signs are related to anemia -Blood transfusions may be needed -Immunosuppressive drugs needed? -Guarded prognosis in dogs --spontaneous remission is possible -Grave prognosis in cats with FeLV |
|
|
Pure Red Cell Aplasia as an Immune mediated disease
|
-Serum Ab directed against RBC progenitor cells
-in cats is associated with FeLV infections -in dogs may be due to drugs, chemicals, infectious agents |
|
|
Anemia of Chronic Renal Failure
|
-Renal disease is often associated with mild to moderate anemia
-Degree of anemia is proportional to degree of uremia -Anemia is more severe in younger animals -Anemia is caused by decreased EPO production |
|
|
Causes of Anemia in Chronic Renal Failure
|
-Decreased EPO production due to kidney damage
-Uremic toxins inhibit bone marrow and response to EPO --uremic toxins sit on platelet surface and cause thrombocytopenia -Decreased RBC survival -Blood loss from GI ulceration and thrombocytopathia -Impaired Fe utilization |
|
|
EPO and anemia of chronic disease
|
-EPO should increase as anemia increases
-Since kidney is damaged, no EPO is produced |
|
|
Characteristics of Anemia of Chronic renal failure
|
-Nonregenerative normocytic normochromic anemia
-Usually results in mild to moderate anemia -Anemia may be masked by dehydration -Crenated RBCs may be present -Thrombocytopathia due to uremia --prolonged buccal mucosal bleeding time -Erythroid marrow hypoplasia -Low serum EPO levels -Renal disease is rarely associated with erythrocytosis |
|
|
Treatment for Anemia of Chronic Renal Failure
|
-Supportive blood transfusion |
|
|
Polycythemia
|
-Increase in total RBC mass
-Clinically = erythrocytosis -Dogs: PCV more than 55% -Cats: PCV more than 46% -Varies from patient to patient -Splenic contraction is NOT the cause |
|
|
Absolute polycythemia
|
-Increase in RBC mass
-Can be primary or secondary -Normal or increased blood volume -No signs of dehydration -Normal plasma protein concentration -Normovolemia or hypovolemia |
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Relative polycythemia
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-Proportional increase in RBCs due to decreased fluids in vasculature
-Dehydration -Adipsia -Diarrhea -Skin burns -Hypovolemia -Increased plasma proteins |
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Primary absolute polycythemia
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-EPO independent increase in RBC mass
-Polycythemia vera -EPO defect or mutation, EPO receptor defect or mutation -Not well-defined in animals -Diagnosis of exclusion -No cardiopulmonary or renal issues, no underlying disease -No cyansosis |
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Secondary absolute polycythemia
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-EPO dependent increase in RBC mass
-Increased EPO levels in the serum -Cardiopulmonary disorders -Renal hypoxia or EPO producing tumors -Can be appropriate or inappropriate |
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EPO
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-Produced in the kidneys
--renal peritubular interstitial cells |
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Appropriate secondary absolute polycythemia
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-Increase in RBC mass due to EPO due to systemic hypoxia
-Body senses that there is not enough O2 and responds by producing more RBCs -Can be due to elevation/altitude -Cardiovascular defects --tetralogy of fallot --reversed R-L patent Ductus arteriosus --Ventricular septal defects --other cardiopulmonary disorders -Methemoglobinemia |
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Inappropriate secondary absolute polycythemia
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-Increase in RBC mass due to EPO, due to local hypoxia or neoplasia
-Tumor produces EPO-like product or EPO |
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Clinical Signs of Absolute polycythemia
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-Hyperemic mm
-Tortuous blood vessels -Cyanosis in rare cases -Epistaxis and bleeding -Neurological disturbances (coma, behavior changes, convulsions) -Cardiopulmonary signs (murmur, dyspnea, tachycardia) -Renal abnormalities (cysts, tumors) -Enlarged organs -Tumors |
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Serum EPO concentration
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-Primary polycythemia: EPO will be low to normal
-Secondary polycythemia: EPO will be normal to high --EPO increase maybe intermittent and mild --highest EPO levels with renal tumors -Elevated serum EPO rules out primary polycythemia -Normal EPO concentration is not diagnostic for Polycythemia vera |
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Treatment for Polycythemia
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-Absolute: phlebotomy
--also possibilities for drug therapy -Relative: rehydration |
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Phlebotomy
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-Treatment for absolute polycythemia
-Bleed 10-20 ml/kg per day -Target PCV should be 50-60% in primary cases -No fluid replacement is generally needed -Hyperviscosity may make collection difficult initially -Blood that is collected should not be used for transfusions -Re-phlebotomize every 1-2 months after initial treatment -Fe deficiency may slow regeneration |
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Other therapy for Absolute polycythemia
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-Exercise restriction |
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Hydroxyurea
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-Can be used as treatment for absolute polycythemia when phlebotomy fails long-term |
