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59 Cards in this Set
- Front
- Back
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What is normal platelet life span?
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10d
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Normal platelet count
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150,000 - 400,000/mm^3
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What is GpIIb-IIIa?
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Platelet surface protein that binds to fibrinogen, which binds other platelets
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Symptoms of platelet hypofunction
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epistaxis
gum bleeding bruising heave menses petechiae NOT hematomas or bleeding into joints |
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Effects of abnormal platelet activation:
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strokes
heart attacks gangrenous limbs |
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When evaluating thrombocytopenia, first r/o what?
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Pseudothrombocytopenia - lab artifact that must be confirmed on blood smear
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Three catagories of causes of thrombocytopenia
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Underproduction
Peripheral destruction Splenic sequestration |
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Three causes of platelet underproduction
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Marrow failure (myelodysplasia, aplastic anemia, vitamin deficiencies)
Marrow infiltration (tumors, etc) Marrow toxins (drugs, radiation) |
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What are the non-immune causes of peripheral destruction of platelets?
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DIC
TTP |
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DIC is characterized by:
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1. Abnormal activation of coagulation
2. Generation of thrombin 3. Consumption of clotting factors 4. Destruction of platelets 5. Activation of fibrinolysis |
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How is DIC diagnosed?
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1. Elevated PT
2. Elevated PTT in advanced cases 3. Low platelets 4. Low/falling fibrinogen 5. Elevated fibrin degradation products or D-Dimers 6. Few schistocytes on blood smear |
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Why is PT elevated in DIC?
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B/c of consumption of Factor VII, which has half-life of 4 hours
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What are the etiologies of DIC?
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Gram negative sepsis
Severe burns OB disasters Certain leukemias or tumors Shock Insect or snake venoms |
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What are supportive measures that can be used to treat DIC?
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Tx of platelets
Clotting factors Fibrinogen +/- low dose heparin to halt thrombin generation |
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What are the characteristics of TTP?
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1. Abnormal activation of platelets and endothelial cells
2. Fibrin deposition in the microvasculature 3. Peripheral destruction of platelets and red cells |
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What are the diagnostic features of TTP (The Pentad)?
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1. Microangiopathic hemolytic anemia (MAHA) - MUST BE PRESENT
2. Low platelets - MUST BE PRESENT 3. Fever 4. Neurological manifestations 5. Renal manifestations (hematuria, proteinuria, increased BUN/creatinine) |
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What are the hematological features of MAHA?
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1. Elevated LDH
2. Elevated bilirubin 3. Schistocytes on the peripheral smear |
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What is the etiology of TTP?
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Sporadic cases due to antibody against protease that cleaves ultra-large molecular weight multimers of von Willebrand's factor; ultra-large vWFs lead to abnormal platelet activation
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What are drugs that can cause TTP?
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Ticlopidine
Quinine Cyclosporine Tacrolimus Gemcitabine |
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What percentage of pts that survive TTP will relapse within 10 years?
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33%
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What is the treatment for TTP?
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Plasma Exchange
Remove all enciting agents |
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Should platelet transfusions be used to treat TTP?
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ABSOLUTELY NOT
doing so only fuels the fire |
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What are the unique features of TTP/HUS?
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Fewer neuro sequelae, but more renal manifestations
Usually precipitated by diarrheal illness, esp E. coli O157:H7 or Shigella Seen more in pediatric patients May respond less well to plasma exchange |
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What drugs classically induce thrombocytopenia?
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1. Beta-lactam antibiotics
2. Trimethoprim-sulfamethoxazole and other sulfa drugs 3. Quinine/quinidine 4. Heparin 5. Abciximab (ReoPro) |
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What is the platelet response seen in HIT?
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Platelets fall 30-50% 7-10d after heparin is started
PLATELET COUNTS DO NOT HAVE TO BE ABNORMAL |
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What is the initial treatment for ITP?
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Corticosteroids (prednisone)
IVIg if more rapid therapy needed |
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What is the second-line therapy for ITP and how often is it needed?
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Splenectomy
2/3 of pts relapse after steroid taper |
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What are the possible causes of splenomegaly?
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1. Portal hypertension
2. Malignancy 3. Infiltrative diseases 4. Infectious diseases 5. Chronic hemolytic diseases (hemoglobin C) |
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What are the congenital causes of qualitative platelet disorders?
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1. Glanzmann's thrombaesthenia
2. Bernard-Soulier |
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What are the causes of acquired causes of qualitative platelet disorders?
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1. Uremia
2. Drugs (ASA, NSAIDS) 3. Herbs (ginkgo, garlic, Vit E) 4. Myeloproliferative diseases |
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What is the Diff Dx for eosinophilia?
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NAACP
1. Neoplasm 2. Allergy/Asthma 3. Addison's disease 4. Collagen vascular disease 5. Parasites |
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Pale pink granular cytoplasm with condensed, segmented nucleus = ________
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Neutrophil
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Granulocytes with large, refractile, orange-pink granules; nucleus is typically bilobed = ________
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Eosinophil
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Large, dark blue granules which overlie the nucleus = ________
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Basophil
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Oval nucleus, with a thin rim of blue cytoplasm = ________
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Lymphocyte
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Folded nucleus with uneven countour; slate grey cytoplasm; there may be vacuoles = ________
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Monocyte
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What are the functions of PMNs?
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Chemotaxis
Phagocytosis Killing of phagocytosed bacteria |
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What are the functions of eosinophils?
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Chemotaxis
Phagocytosis Killing of phagocytosed bacteria Antibody dependent damage to parasites Regulation of immediate-type hypersensitivity reactions |
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What are the functions of basophils?
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Mediation of immediate-type hypersensitivity responses
Modulation of inflammatory responses |
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What are the functions of lymphocytes?
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Immune regulation and production of hematopoietic growth factors
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What are the functions of monocytes?
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Chemotaxis
Phagocytosis Killing of some microbes Antigen presentation |
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What are the major causes of elevated neutrophil counts?
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Acute Infections
Acute Inflammation Myeloproliferative disorders Leukocyte adhesion deficiency Drugs (corticosteroids, G-CSF, lithium) S/p splenectomy |
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What drugs can cause neutropenia?
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Anti-psychotics
Anti-epileptics Anti-thyriod Some antibiotics |
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What drugs can cause agranulocytosis?
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Clozapine
Propythiouracil Anti-convulsants Sulfa and chloramphenicol antibiotics |
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What are significant non-drug causes of neutropenia?
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Infection, especially with CMV
Systemic lupus erythematosus Felty's syndrome (rheumatoid arthritis, splenomegaly, and neutropenia) |
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What are significant causes of lymphocytosis?
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Viral infection
Bacterial infection, esp pertussis CLL |
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What are significant causes of lymphocytopenia?
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Immunodeficiencies (HIV/AIDS)
Immunosuppressive drugs Lymphomas Granulomatous diseases, including TB and sarcoidosis |
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What are the significant causes of acquired defects in neutrophil function?
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Corticosteroid use
Alcoholism Leukemias Myelodysplasia Myeloproliferative disorders |
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Where is von Willebrand’s factor located?
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Subendothelium
Inside platelets (secreted) |
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What agents can activate platelets?
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Thrombin
Thromboxane (TxA2) Collagen ADP Epinephrine Serotonin |
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What is dificient in Hemophilia A?
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Factor VIII
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What is dificient in Hemophilia B?
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Factor IX
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Hemophiliacs commonly suffer from erosion of what joint?
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The knee
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What is the most common hereditary bleeding disorder?
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von Willebrand Disease
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What are the two functions of vWF?
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Carrier molecule for F.VIII
Activation of platelet adhesion |
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What are common causes of acquired coagulopathy?
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Vitamin K deficiency (F.II, F.VII, F.IX, F.X, proteins C and S)
Liver disease Thrombocytopenia from hypersplenism DIC |
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A delayed PT indicates a deficiency or defect in what?
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Fibrinogen
Prothrombin Factor V Factor X Factor VII |
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A delayed PTT indicates a deficiency or defect in what?
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Fibrinogen
Prothrombin F.V F.X F.VIII F.IX F.XI F.XII |
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What do the results of the mixing study (aPTT) indicate?
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If it corrects the APTT, pt has coagulation factor deficiency
If it does not correct the APTT, pt has a factor inhibitor |
