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409 Cards in this Set
- Front
- Back
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Where does hematopoiesis occur in adults?
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Sternum, proximal long bones, and pelvic bones
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What is the normal minimum of bone marrow cellularity in adults?
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20-30%
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What are the 6 myeloid and 3 lymphoid cells seen in peripheral blood?
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Myeloid: Erythrocytes, Platelets, Monocytes, Neutrophils, Eosinophils, and Basophils.
Lymphoid: B-cells, T-cells, NK cells |
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What is the ratio of myeloid to erythroid production during normal production
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3 myeloid cells: 1 erythroid cell
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Where and when, embryologically, does hematopoiesis begin? What types of cells are involved
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At week 3, in the embryo's yolk sac, mesenchymal cells differentiate into primitive blood cells and primitive endothelial cells
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Where does hematopoeisis occur during gestation and post-partum?
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First 6 weeks: Yolk sac
6-18 weeks: Liver 18-30 weeks: Liver and spleen 30 week to birth to 8 wk old infant: Liver, spleen, and bone marrow After 10 week old infant: Bone marrow only |
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Name the 5 precursors to mature erythrocytes and describe the general nucleic and cytoplasmic changes during maturation
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Pronormoblast, basophilic normoblast, polychromatophilic normoblast, orthochromatic normoblast, reticulocyte
Chromatin is originally fine and lacy and condenses down until it is expelled at the reticulocyte stage Cytoplasm is originally basophilic and becomes magenta with hemoglobin accumulation |
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Describe the size and shape of erythrocytes and explain how they contribute to the cell function
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Erythrocytes are ~8µm and exhibit a biconcave shape
The shape allows for a high level of deformity through small blood vessels and the biconcavity increases surface area, increasing gas exchange |
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Name the 3 types of mature granulocytes and describe their general appearance in a blood smear
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Neutrophils, Polymorphonucelar neurtophils (PMN), or Segmented neutrophils (Segs): 3 lobes with non-descript granules
Eosinophils:2 lobes with pink granules Basophils: 3 lobes with blue granules |
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Name the 2 common and 4 differentiated precursors of granulocytes in order
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Myeloblasts become promyelocytes which then differentiate into neutrophilic, eosinophilic, or basophilic myelocytes, which become metamyelocytes, bands, and finally mature cells
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What are the main functions of neutrophils?
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They fight bacterial infections and phagocytize small particles. They surround the particle, release granule contents dropping the pH, killing and digesting the bacteria.
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What are the main functions of eosinophils?
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They respond to parasitic infections, are involved in allergic reactions, vasculitis, and the occasional hematologic malignancy
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What role do basophils play?
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They are involved in the allergic response. They have IgE receptors and when an allergen binds, they release histamine
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What function do monocytes serve and where to they carry out their role?
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They migrate to the tissues where they become macrophages. They also invest fungi, mycobacteria, and battle pyogenic bacteria
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What clusters of differentiation are associated with B-cells?
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CD10, CD19, CD20, CD79a, sIg κ/λ
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What clusters of differentiation are associated with T-cells?
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CD3, CD4, CD5, CD7, CD8
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What clusters of differentiation are associated with NK-cells?
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CD16, CD56
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What is the immunophenotype of early B-cells?
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TdT, CD10, CD19, CD20, CD79a
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What is the immunophenotype of early T-cells?
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TdT, CD7, CD3, CD5, CD4 & CD8
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What is the lymphoid organization in the white pulp of the spleen?
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T-cells are localized in periarterial lymphatic sheaths. B-cells comprise a majority of the lymphoid nodule
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A person with Type A blood has anti-bodies for what type of blood?
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Anti-B antibodies
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A person with Type B blood has anti-bodies for what type of blood?
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Anti-A antibodies
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A person with Type AB blood has anti-bodies for what type of blood?
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No antibodies
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A person with Type O blood has anti-bodies for what type of blood?
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Anti-A and Anti-B antibodies
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What blood type is the universal recipient and universal donor?
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Universal recipient is AB because they have no antibodies. Universal donor is O because they have no surface antigens
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What is the yield form 1 unit of whole blood?
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1 unit each of packed RBcs, random donor platelets, plasma, and cryoprecipitate
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How much does 1 unit of PRBCs raise a Hb and Hct?
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Increases Hb by 1 g/dL and Hct by 3%. Double for pediatric patients
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Where are the different portions of blood stored?
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PRBCs = Refrigerator
Platetes = Room temperature Plasma = Frozen Cryoprecipitate = Frozen |
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What are some reasons plasma are transfused?
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Disseminated Intravascular Coagulopathy (2 units), to reverse warfarin
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What is the D antigen?
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Rh±. Important during pregnancy. Mother can develop anti-Rh IgG antibodies that can cross the placenta and cause hemolytic disease of the newborn.
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How is a cross match test performed?
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Mix patient's serum with donor RBCs, if they clump the unit is incompatible
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What is the difference between the direct and indirect Coombs' Test?
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In indirect, the patient's antibodies bind the donor RBCs and the anti-IgG reagent causes agglutination if the patient antibodies bound the donor RBCs is present. The direct Coombs' the patient's blood is drawn and tested directly with antibodies.
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What are the most common risks of infection from transfusion?
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HBV, HCV, HIV, HTLV, WNV, Syphilis, Chagas, Babesiosis, Malaria
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What are some common signs and symptoms of an infusion reaction?
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Fever, chills, local pain, blood pressure changes, respiratory distress, skin changes (urticaria, flushing, edema), nausea / vomiting, dark urine or jaundice, bleeding
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What are three ways to test for hemolysis?
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Visually (specimen and unit), labs (total and conjugated bilirubin, LDH, plasma hemoglobin, haptoglobin), urinalysis
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What is the etiology, symptoms, and management of Acute Hemolytic Transfusion Reaction?
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Transfusion of ABO incompatible blood. Fever, chills, back pain, dyspnea. Stop and support (fluids and pressors to elevate BP)
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What is the etiology, symptoms, and management of Delayed Hemolytic Transfusion Reaction?
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Recepient forms antibodes against transfused RBCs. Fever/chills, decreasing Hct, jaundice, dark urine. Monitor renal function, restore Hct
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What is the etiology, symptoms, and management of Febrile Non-Hemolytic Transfusion Reaction?
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Recipient WBCs react with donor WBCs or platelets leading to cytokine accumulation (TNF-α, IL-1, IL-6, IL-8). Fever, chills, headache, tachycardia, myalgia. Administer antipyretics, premedicate with Tylenol.
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What is the etiology, symptoms, and management of Urticarial Transfusion Reaction?
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The recipient is sensitized to the donor plasma protein. Urticaria, flushing, itching, erythema. Stop or slow transfusion, administer antihistamine.
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What is the etiology, symptoms, and management of an Anaphylactic Transfusion Reaction?
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IgA deficient recipient with IgA antibodies is given IgA+ blood. Anaphylactic shock, hypotension, flushing rash, chills, coughing, respiratory distress, abdominal cramping, vomiting, diarrhea, LOC. Stop, ABCs, Epinephrine, steroids, O2, pressors
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What is the etiology, symptoms, and management of Transfusion Related Acute Lung Injury?
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Donor B-cell and T-cell antibodies react to recipients WBCs (HLA and neutrophil specific). Acute respiratory insufficiency without heart failure, dyspnea, tachycardia, bilateral "white-out" CXR. Stop, may need intubation.
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What is the etiology, symptoms, and management of transfusion associated graft v. host disease?
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Donor lymphocytes grafted into recipient bone marrow mount immune response against recipient cells. Rash, diarrhea, hepatosplenomegaly, pancytopenia. High dose steroids.
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What is the etiology, symptoms, and management of a septic transfusion reaction?
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RBC (Yersinia, citrobacter, pseudomonas, E. coli), platelets (GP cocci, pasteuralla, yersinia). "Warm shock" - fever and hypotension. Stop, immediately treat with IV antibiotics and pressor support.
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What is the etiology, symptoms, and management of an Transfusion Associated Circulatory Overload?
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Fluid administered faster than the circulatory system can handle (CHF, pediatrics, elderly). Cough, dyspnea, tachycardia, rales, distended neck veins, hypertension, headache. Stop, treat for pulmonary edema (O2, diuretics, morphine)
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What is the etiology, symptoms, and management of an Thermal/Mechanical Hemolysis?
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Excess heat/cold, using hypotonic solution. Acute hemolysis transfusion or asymptomatic except hemoglobinuria / hemoglobinemia. Stop, give fluids
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What is the etiology, symptoms, and management of an Hypothermia?
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Rapid infusion of cold blood (trauma, OR case). Hyperkalemia or hypocalcemia leading to ventricular arrythmias or impaired hemostasis. Warm blood during massive transfusion.
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What are normal ranges for WBC, RBC, Hb, Hct, MCV, MCHC, RDW, and Platelets
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WBC = 4.8-10.8
RBC = 4.7-6.1 Hb = 14-18 g/dL Hct = 42-52% MCV = 80-100 fL MCHC = 33-37 pg RDW = 11.5-14.5% Platelets = 140-360 |
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What is the normal order of prevalence of WBC types?
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Never Let Men Eat Bologna.
Neutrophils (60-70%), Lymphocytes (30-40%), Monocytes (2-10%), Eosinophils (2-4%), Basophils (<1%). |
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What pathologies are target cells associated with?
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Hemoglobinopathies, thalassemias, iron deficiency anemia, drug-induced hemolytic anemia, liver disease
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What pathologies are Schistocytes associated with?
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Disseminated Intravascular Coagulation, Thrombotic Thrombocytopenia Purpura
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What pathologies are Rouleaux cells associated with?
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Multiple Myeloma, Plasma cell leukemia, Infection
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What pathology is Howell Jolly Bodies associated with
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Surgical or functional asplenia. Nuclear chromatin normally filtered out remains.
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What levels are measured in a BMP and what additional levels are added with a CMP
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Sodium, Potassium, Chloride, CO2, BUN, Creatinine, Glucose, Calcium. CMP adds Total protein, Albumin, AST, ALT, Alkaline Phosphatase, Total Bilirubin.
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What chromosome are a-globin genes on?
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Chromosome 16
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What chromosome are b,d, and g-globin genes on?
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Chromosome 11
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What globin varieties do humans have two copies of?
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α and ϒ
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What is the composition of Hemoglobin A?
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2a chains and 2b chains
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What is the composition of Hemoglobin A2?
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2a chains and 2d chains
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What is the composition of Hemoglobin F?
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2a chains and 2g chains
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Which direction does lowering pH push Hb's oxygen affinity curve?
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To the right. If the environment is acidic, you want Hb to release O2, shifting the curve to the right ensures that at any PO2 the is less O2 saturation of Hb. Hb releases more O2 to the tissues.
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What is the function of 2,3-bisphosphoglycerate in Hb and it's O2 affinity?
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2,3-BPG stabilizes Hbs tense, deoxygenated state, meaning a higher PO2 is needed to saturate the same amount of Hb, shifting the curve to the right.
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What are the three main points of the Embden-Meyerhof Pathway?
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- The reaction need 2 ATPs to get started but yields 4 ATPs for a net of +2.
- 2,3-BPG stabilizes the taunt, deoxygenated state of Hb, allowing more O2 to remain in the tissues, shifting Hb's curve to the right. - Methemoglobin, with Fe3+, is converted to hemoglobin, with Fe2+, allowing the globin molecule to transfer an electron to O2 |
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Why is the Hexose monophosphate shunt important?
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G6PD is responsible for converting NADP to NADPH. NADPH metabolizes gluthathione, and reduces H2O2 to H2O reducing oxidative damage
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What are the three general causes of intracorpuscular hemolysis?
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Cell membrane problems (hereditary spherocytosis or elliptocytosis), Enzyme problems (G6PD deficiency, pyruvate kinase deficiency), Hemoglobin problems (Thalassemias, hemoglobinopathies)
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What are the general causes of extracorpuscular hemolysis?
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Antibodies against RBCs, enlarged spleen (sludging, entrapment, and destruction), intravascular trauma, chemical exposure (ROS), infection (malaria, babesiosis)
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Where does extravascular hemolysis occur?
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In the liver or spleen
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What are some causes of intravascular hemolysis?
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Valvular shear stress, lysis from bacterial toxins, direct trauma, osmotic lysis, complement-induced lysis
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What abnormal lab results suggest intravascular hemolysis?
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Decreased free haptoglobin, hemoglobinemia, hemoglobinuria, hemosiderinuria
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What cells are responsible for extravascular hemolysis?
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Monocytes and macrophages in the liver and spleen
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What are the expected changes in LDH, serum haptoglobin, reticulocyte count, total and indirect bilirubin in the case of hemolysis?
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LDH = increases
Serum haptoglobin = decreases Reticulocyte count = increases Total and indirect bilirubin = increase |
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What is the deficit in hereditary spherocytosis?
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There is no binding between ankyrin and spectrin, this leads to ineffective membrane synthesis
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What cytoplasmic granules are common to all granulocytes?
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Azurophilic granules (lysosomes)
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What accounts for the basophilia of the cytoplasm in early stages of erythrocyte development and the eosinophilia in later stages
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Abundance of rRNA for ribosomes make the basophilic stain and the Hb protein formed leads to the eosinophilic staining later.
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How does prematurity affect the physiologic anemia of the newborn?
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Premie babies haven't developed the Fe stores or the appropriate levels of HbF to compensate and counteract the bottoming out from physiologic anemia
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What are the 3 most common causes of anemia in the newborn?
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Hemorrage (twin-twin, feto-maternal), Congenital (hemoglobin, membrane, enzymopathies), Acquired (ABO incompatibility, Rh disease)
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What is the difference between Diamond Blackfan and Fanconi syndromes?
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Diamond Blackfan is a purely red cell plasia. Fanconi is an aplastic anemia, affecting white and red blood cells, as well as platelets.
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What are some signs that would make you suspect an anemia?
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Fatigue, pallor, dyspnea, tachycardia, postural hypotension, jaundice, pica, koilonychia
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What are the 3 general mechanisms of anemia?
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Decreased RBC production, increased RBC destruction, bleeding
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What is the common mechanism among microcytic anemias?
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Defective hemoglobin synthesis or function
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What is the common mechanism among macrocytic anemias?
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Defective DNA synthesis or function
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What enzyme is responsible for binding Iron to the porphyrin ring and what oxidative level of iron is needed?
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Ferrochelatase binds a Fe2+ into the protoporphyrin ring
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What are three general ways hemoglobin synthesis can be abnormal?
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Decreased iron availability/utilization, disordered heme synthesis, disordered globin synthesis
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What role does hepcidin play in iron metabolism?
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In cases of iron deficiency (anemia, hypoxia), hepcidin is downregulated, allowing ferroportin to release iron recycled by macrophages and absorbed by the gut. In cases of high iron levels (like with inflammation), hepcidin is upregulated and binds to both the gut and macrophages, blocking release and increasing iron storage.
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What is a common way children can become iron deficient?
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By changing over to cow's milk from breast milk. Humans can't readily absorb iron from cow's milk.
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What are 2 main causes of iron deficiency in adults?
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Blood loss (GI malignancy, menorrhagia), increased requirements (pregnancy, lactation)
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What will an iron panel show if anemia is caused by iron deficiency?
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Serum iron, ferritin, and iron saturation will be decreased, Transferrin Iron Binding Concentration will be increased.
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What are some hereditary and acquired causes of sideroblastic anemia?
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X-linked and autosomal recessive disorders. Drugs (isoniazid), toxins (alcohol, lead), neoplasm (MDS)
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What are sideroblasts?
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Abnormal, atypical, nucleated erythroblasts
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What are the four ways chronic disease can lead to anemia?
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Chronic inflammation activates monocytes and T-cells which increases hepcidin synthesis in the liver, and erythropoietin release by the kidney. These cytokines also inhibit erythroid proliferation in the bone marrow and increases hemophagocytosis.
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What is the difference between a thalassemia and a hemoglobinopathy?
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Thalassemias are disorders of quantity of globin chains while hemoglobinopathies are disorders of quality of globin chains.
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What type of Hb is increased in a B-Thalassemia?
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A2 (aadd) with little or no b chains present there will be an increase in A2 globin as well as an excess in a globin chains
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What is the clinical presentation of someone with B-Thalassemia trait?
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Mild anemia, normal Fe stores, HbA2 will be slightly increased on electrophoresis
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What is the clinical presentation of someone with Cooley's Anemia?
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B-Thalassemia Major. Severe anemia (needs transfusions), increased iron stores, elevated HbF on electrophoresis, absent HbA. Thalassemic facies (frontal bossing, maxillary hyperplasia), splenomegaly, osteopenia, Fe overload (cirrhosis, endocrinopathies, heart failure)
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What are the two types of Hb variants possible with A-Thalassemia?
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Hb Barts - gggg (Hydrops Fetalis)
Hb H - bbbb |
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What are the ethnic differences in A-Thalassemias?
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Africans are more likely to have a single deletion on each chromosome 16. SE Asians are more likely to have both deletions on the same chromosome 16, increasing the likelihood of hydrops fetalis.
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What is the clinical presentation of someone with A-Thalassemia trait?
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Mild microcytic, hypochromic anemia, target cells, Hb Barts on newborn screening because the levels of a globin is severely lacking
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What is the clinical presentation of someone with Hemoglobin H disease?
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Moderate to severe hemolysis, microcytic, hypochromic anemia, osseus changes, splenomegaly. Treat with transfusions and iron chelation
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What is the clinical presentation of a newborn with hydrops fetalis?
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Incompatible with life, death in the 3rd trimester, due to Hb Barts having and incredibly high affinity for O2 depriving the tissues of O2. Severe hemolysis, massive hepatosplenomegaly, anasarca, extreme extramedullary hematopoiesis
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What is the cause and morphologic pattern of megaloblastic anemia?
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Defective DNA synthesis (unbalanced cell growth, impaired division). Immature nucleus with mature cytoplasm, hypersegmented neutrophils and large cells
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What are the most common causes of megaloblastic anemia?
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B12 and folate deficiency
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What can one determine using methylmalonic acid and homocysteine testing?
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Methylmalonic acid is not dependent on folate, so if methylmalonic acid is elevated, the patient must have a B12 deficiency. Homocysteine levels are dependent on Folate and B12, so if homocysteine levels are high, you cannot determine whether the patient has a folate or B12 deficiency.
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How do B12 and folate deficiencies cause a megaloblastic anemia?
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Both folate and B12 are necessary to convert deoxyuridylate to thymidylate in purine synthesis and normal DNA production
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What are common sources of B12 and folate?
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B12 = fish, eggs, poultry
Folate = leafy greens |
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What factor is involved in Cobalamin absorption, where is it generated, and where does cobalamin absorption occur?
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Intrinsic factor is generated and released in the stomach and leads to cobalamin absorption in the small intestine
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What is pernicious anemia and how is is diagnosed?
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Pernicious anemia is an autoimmune destruction of gastric cells or intrinsic factor and it is diagnosed with anti-IF antibodies, (previously the Schilling test)
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What are some of the neuropsychiatric manfestations of B12 deficiency?
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Peripheral neuropathy, dorsal column defects (loss of position and vibratory sense, ataxa), subacute combined degeneration of the spinal cord (demyelination causing impaired motor function and spasticity), and psychiatric symptoms (dementia, psychosis)
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What are some non-megaloblastic caused of macrocytic anemia?
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Drugs (dilantin, sulfa, AZT, methotrexate), alcohol, liver disease, thyroid disease, Myelodysplastic syndrome
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What is the mutation responsible for Sickle Cell Anemia?
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A single nucleotide polymorphism causing a glutamic acid to be substituted for valine at codon 6 of the B-globin gene.
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What is the phenotypic mutation that causes sickle cell anemia?
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When valine is substituted for a glutamic acid in the b-globin chain, the deoxygenated form of the hemoglobin molecule becomes unstable and predisposed to polymerize into long rods making the RBC rigid, inflexible, and sickle-shaped. These mutated RBCs also have shorter lifespans.
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What are common complications of sickle cell disease?
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Pain crises = Tissue/bone infarcts caused by vaso-occlusions
Chronic hemolytic anemia = gallstones, risk of red cell aplasia from Parvovirus, decreased vascular tone Increased infection susceptibility = functionally asplenic, infarcted tissue Acute chest syndrome = vaso-occlusion with reperfusion injury and lung parynchema death Stroke, renal insufficiency |
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What are the treatments utilized for sickle cell patients?
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Transfusions, hydroxyurea, folic acid, vaccines, pain medication
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How do you calculate the absolute neutrophil count?
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ANC = #PMNs + #bands
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Where in the peripheral blood are neutrophils stored and how can they be mobilized?
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More than half the neutrophils are attached to the vascular endothelium. These stores can be demarginated by administering epinephrine or steroids.
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What are some non-malignant causes of leukocytosis with neutrophilia?
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Infection, stress, smoking, pregnancy, MI, general marrow stimulation (hemolysis)
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What is meant by "left shift" and where is it commonly seen?
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An increase in immature WBCs, especially bands, commonly seen in bacterial infection
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What is a common non-malignant cause for leukocytosis with lymphocytosis?
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Viral infections: mono (EBV), CMV, HIV, mumps, varicella, influenza, hepatitis, rubella, measles
Other infections: Bordetella pertussis, bartonella henselae, toxoplasmosis, babesiosis Hypersensitivity, stress |
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What is a common non-malignant cause for leukocytosis with eosinophilia?
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Secondary eosinophilia = infection (parasite, aspergillus), allergic, mediations, toxins, autoimmune disorders
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What is a common non-malignant cause for leukocytosis with basophilia?
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Hypersensitivity reactions, ulcerative colitis, rheumatoid arthritis, hypothyroidism, infections (viral, TB, worm)
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What is a common non-malignant cause for leukopenia with neutropenia?
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Normal variation (african-americans, nonsmokers), pseudoneutropenia (more marginated neutrophils), infections (mono, HBV, HIV), medications, immune mediated (Autoimmune hemolytic anemia, ITP), congenital
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What is a common non-malignant cause for leukopenia with lymphopenia?
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Decreased production (AIDS, aplastic anemia), increased destruction (steroids, chemotherapy, radiation), congenital disorders
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How does thrombopoietin regulate platelet production?
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Thrombopoietin is produced in the liver and in the presence of normal platelet numbers, platelets bind free thrombopoietin decreasing TPO amounts reaching the bone marrow stimulating platelet production. During thrombocytopenia, there are fewer platelets to bind TPO, leaving higher amounts to reach the bone marrow and stimulate thrombopoiesis.
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What make up the contents of platelets two types, alpha granules and dense bodies?
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Alpha granules = Fibrinogen, von Willebrand factor, and platelet factor 4
Dense bodies = ADP (activates neighboring platelets) and serotonin (a vasoconstrictor) |
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What are the 3 "As" of platelet function?
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Adhesion to non-platelet surface, activation of platelets to discharge granule contents, and aggregation of platelets to one another
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How do activated platelets adhere to the endothelium?
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Exposed subendothelial collagen binds vWF, which has a binding site for platelets (GpIb)
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What elements are responsible for platelet aggregation?
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Activated platelets aggregate by creating a bridge with Gp IIb/IIIa and fibrinogen in the presence of Calcium
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Name 5 functions of platelets.
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Form mechanical plugs during primary hemostasis, locally release vasoconstrictors to decrease blood flow, catalyze fibrin clot formation, initiate tissue repair, regulate local inflammation
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Name 4 mechanistic causes of thrombocytopenia.
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Decreased platelet production, increased platelet consumption, abnormal platelet distribution, dilutional loss
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What are some causes of platelet production failure?
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Drugs, chemicals, viral infections, general bone marrow failure (cytotoxic drugs, radiation, marrow infiltration, HIV)
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What are some causes of increased platelet consumption?
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Immune = ITP, infections (HIV, malaria), drug-induced, heparin
Disseminated intravascular coagulation, thrombotic thrombocytopenic purpura |
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What is the presentation, mechanism, and treatment of immune thrombocytopenic purpura?
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Abrupt onset bruising, petechiae, and/or mucosal bleeding in a previously healthy person. May follow and infection (URI or GI). The body forms antibodies against autoplatelets, signalling platelets for macrophage phagocytosis. Immune system (steroids, splenectomy, IVIg), give TPO agonist
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What is the mechanism of heparin induced thrombocytopenia
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Following a treatment with heparin, the body develops antibodies to the heparin-platelet factor 4 complex, greatly increasing the activation rate of platelets causing venous, arterial, and microvascular thrombosis
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What is the clinical pentad of thrombotic thrombocytopenic purpura?
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FAT-RN. Fever, anemia, thrombocytopenia, renal dysfunction, neurologic deficits
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What would a peripheral smear look like from a patient with TTP?
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Schistocytes (RBCs are destroyed when they run into thrombosis from uncleaved vWF) and few platelets
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What is the pathophysiology of Thrombotic thrombocytopenic purpura?
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Defective or absent ADAMTS13 is unable to cleave vWF allowing long "sticky" forms of vWF to trap platelets and cause thrombi. These clots lead to end-organ damage and the pentad of clinical features (fever, anemia, thrombocytopenia, renal dysfunction, neurologic deficits)
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Do you transfuse platelets to treat Heparin induced thrombocytopenia or thrombotic thrombocytopenic purpura?
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No, platelets will only exacerbate the mechanism of injury
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Name the 3 main disorders associated with bone marrow failure.
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Aplastic anemia, paroxysmal nocturnal hemoglobinuria (no Gp-I anchor protein to allow CD55 or CD59 to bind and protect RBC from MAC), myelodysplastic syndrome
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What cell is damaged in aplastic anemia?
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The pluripotent stem cell, leading to a pancytopenia
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What are some congenital and acquired causes for aplastic anemia?
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Congenital (Fanconi anemia), acquired (radiation, chemo, medications, viral infections - HIV,EBV, immune disorders like lupus or GvHD)
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What is the pathophysiology of Paroxysmal nocturia hemoglobinuria and how can you treat it?
|
Patients have a defect in the PIG-A gene leading to a lack of GpI-anchor proteins. GpI-anchor binds CD55 and CD59 to the surface of the RBC to protect it from complement attack (MAC). The defect leads to hemolysis through the complement cascade. Over time this can develop into a pancytopenia. Administer monoclonal C5 or Eculizumab
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What do the bone marrow and peripheral blood look like in myelodysplastic syndrome?
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Bone marrow will be hypercellular, with abnormal cells. The peripheral blood will have a cytopenia.
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What are the clinical symptoms of myelodysplastic syndrome and what is the underlying reason for these symptoms?
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Cytopenia in the peripheral blood leads to recurrent infections, fatigue, pallor, bleeding, with no splenomegaly
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How many blasts are diagnostic of MDS?
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6-19% blasts
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What is a common genotype with MDS and how do its favorability compare?
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5q- will have a benign clinical course and are responsive to thalidomide and lenalidomide
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What treatments are available for myelodysplastic syndrome?
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Supportive care (Antibiotics, transfusions, growth factors, iron chelators), chemotherapy, monitor for AML transformation
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What are some causes of normocytic anemia?
|
Acute hemorrhage, RBC enzyme defects, RBC membrane defects, bone marrow disorders, hemoglobinopathies, autoimmune hemolytic anemia, anemia of chronic disease
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How do you calculate an MCV and what is its normal range?
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MCV (fl) = Hct/RBC
Its normal range is 80-100 fl |
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How do you calculate an MCH and what is its normal range?
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MCH (pg) = Hb/RBC
Its normal range is 26-33 pg |
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How do you calculate an MCHC, what is its normal range, and how is it used?
|
MCHC (g/dL) = Hb/Hct
Its normal range is 32-36 g/dL and it represents the concentration of Hb in RBC (hyper/hypochromic) |
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What lab test measures anisocytosis and what is its normal range?
|
Anisocytosis or the variation/range in cell volume is measured by the RDW and its normal range is 12-16%
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What are the clinical features of Parvovirus B19 infection in the immunocompetent v immunocompromised host?
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Immunocompetent = "Fifth Disease", low fever, malaise, slapped cheek rash, polyarthropathy
Immunocompromised = Chronic B19 infection, transient aplastic crisis |
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What are two other names for Acute Myeloid Leukemia
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Acute Myelogenous Leukemia, Acute Nonlymphocytic Leukemia
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What cell is defective in AML?
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The myeloblast
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What is the basic pathophysiology of AML?
|
The myeloblast is defective and grows uncontrollably, its maturation is halted, and it inhibits the growth of normal cells
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How do we recognize AML and how is it diagnosed?
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By the presenting symptoms: anemia (fatigue, dyspnea on exertion), thrombocytopenia (petechiae, bleeding), neutropenia (persistent infections). It is diagnosed with a bone marrow biopsy where the aspirate shows >20% blasts and often Auer rods
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How is AML distiguished from ALL?
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Flow cytometry, cytogenetics, or FISH must be performed to determine lineage
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What is the treatment for AML?
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7+3 Cytarabine and daunorubicin. Sometimes etoposide is added (7+3+3). Supportive care is provided (antibiotics, pRBCs, platelets, monitoring tumor lysis syndrome and chemo side effects). Perform nadir. If it didn't work 5+2(+2) of something else.
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What are sludging symptoms, what state are they seen in, and how is it treated?
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Chest pain, shortness of breath, headaches, blurry vision seen in leukostasis (high WBC). Patients are given emergent leukopheresis
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What is given as the consolidation treatment of AML?
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3 booster treatments of high-dose cytarabine on days 1,3, and 5. Patients are discharged with antibiotics.
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What are bad prognostic factors seen in AML?
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Increased age (decreased ability to tolerate chemo, higher incidence of MDR, and antecedent hematologic disorders), secondary AML, genetic factors (5-, 7-, 11q23), not achieving remission after induction chemo
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What are good prognostic factors seen in AML?
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Acute promyelocytic leukemia (t15:17), Inv(16), t(8:21)
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What is t(15:17) diagnostic for and how does this diagnosis differ from AML and what are they at a high risk for?
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Acute promyelocytic leukemia is a defect in the promyelocyte. It tends to be seen in younger patients and they have a better prognosis than AML patients. They have a high risk of DIC and can die from intracranial hemorrhage. They are treated with 7+4+ATRA (Retionic acid which pushes cells to mature)
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What is the most common childhood malignancy?
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Acute lymphocytic leukemia
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What is the epidemiology of ALL?
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White, males, aged 2-5 years
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What are the clinical manifestations of ALL?
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Fatigue, pallor, bruising, bleeding, fever, lymphadenopathy, hepatosplenomegaly, mediastinal mass, musculoskeletal pain
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What are the lab finding of ALL?
|
Leukocytosis or leukopenia depending on progression of the disease, blast may be seen on smear, anemia, thrombocytopenia, tumor lysis
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What is the diagnostic test for ALL?
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25% lymphoblasts in bone marrow biopsy, flow cytometry to determine lineage (ALL v AML, T-cell v B-cell)
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What are the different classifications of ALL and what phenotypic markers are found in each?
|
Pre-pre B-cell: CD19 11q23 rearrangement, infants
Early pre-B-cell: CD19, CD19, common ALL Pre-B-cell: CD19, CD20, cIg, older children B-cell: CD19, CD20, cIg, sIg, Burkitt (must have t8:14 myc/IgH) T-cell: CD7, CD4/8, adolescents, anterior mediastinal mass, CNS |
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What are favorable cytogenetic findings for ALL?
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Hyperdiploidy, t(12:21), trisomies of chromosomes 4, 10, and 17
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What are unfavorable cytogenetic findings for ALL?
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Hypodiploidy, t(4:11) MLL, t(9:22) Bcr-Abl, amplification of chromosome 21, early T-cell precursor ALL (CD1a-, CD8-, weak CD5)
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What is the general treatment regimen for ALL?
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Induction, consolidation, CNS treatment, maintenance
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Where are to havens or sanctuaries for malignant cells to hide?
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CNS and testicles
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What are the 4 causes of impaired host resistance?
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Impaired phagocyte function, impaired cell-mediated immunity, reduced antibody levels, breakdown of mechanical barriers
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What tests are used to determine host defense defects?
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Impaired phagocyte function: ANC <500
Impaired cell-mediated immunity= CD4 count <200 Reduced antibodies= (hypogammaglobulinemia) IgG <800 |
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What are some causes of impaired phagocytic function?
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Diabetes Mellitus II, acute leukemias, steroids, alkylating agents, cytotoxic agents
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What are some causes of impaired cell-mediated immunity?
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HIV, Hodgkin lymphoma, steroids
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What are some causes of reduced antibody levels?
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Multiple myeloma, antimetabolites, alkylating agents
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What are some causes of mechanical barrier breakdowns?
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Vascular insufficiency, trauma, medical procedures,
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Are bacteria, fungi (candida, aspergillus, zygomycetes), viruses (HSV, CMV), and the pneumocystis parasite acquired endogenously or exogenously?
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Bacteria= endogenous
Candida= endogenous Aspergillus= exogenous Zygomycetes= exogenous HSV= endogenous CMV= exogenous Pneumocystis= endogenous |
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What class of antibiotics are appropriate for prophylactic treatment against endogenous organisms in the immunocompromised host?
|
Fluoroquinolins (moxifloxacin, ciprofloxacin, levofloxacin)
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What are some sources of acquiring exogenous organisms by immunocompromised hosts?
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Hands of personnel, air, food, fomites, medical devices
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What quantifies a fever of worry in an immunocompromised host?
|
A single temperature of 38.3 (101) or a temperature of 38 (100.4) for over an hour or on 2 or more occasions in 24 hrs
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What are some microbial causes of fever and skin lesions in the immunocompromised host?
|
Bacteria: S.aureus, GNR (pseudomonas), nocardia, M. tuberculosis
Viruses: HSV, VZV Fungi: Aspergillus, Candida, Cryptococcus |
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What are some microbial causes of fever and CNS findings in the immunocompromised host?
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Bacteria: GPC (S. aureus), GNR, P. aeruginosa, Listeria, Nocardia, M. tuberculosis
Fungi: Cryptococcus, Aspergillus, Zygomycetes, Candida Viruses: VZV, HSV, Papovavirus Parasites: Toxoplasma |
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What are common pathogens that cause pneumonia in patients receiving induction chemo for AML?
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P. aeruginosa, Klebsiella, S. aureus, Aspergillus
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What are common pathogens that cause anorectal lesions in patients receiving induction chemo for AML?
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P. aeruginosa, E. coli
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What are common pathogens that cause pharyngitis in patients receiving induction chemo for AML?
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Normal flora, GNR, Candida, S. aureus
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What are common pathogens that cause esophagitis in patients receiving induction chemo for AML?
|
Candida, CMV, HSV, GNR
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What are common pathogens that cause skin lesions in patients receiving induction chemo for AML?
|
GNR, S. aureus, skin flora, HSV
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What is a common cause of UTIs in patients receiving induction chemo for AML?
|
E.coli
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What is a common cause of hepatitis in patients receiving induction chemo for AML?
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HCV
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What type of pathogen is implicated in infecting patients with a phagocytic cell deficiency?
|
Extracellular pathogens. Pyogenic bacteria (S. aureus, GNR), filamentous fungi (Aspergillus, zygomycetes), candida
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What type of pathogen is implicated in infecting patients with a cell-mediated immune deficiency?
|
Intracellular pathogens. Viruses (HSV, VZV, CMV), parasites (toxoplasma, pneumocystis), mycobacteria, fungi (candida, cryptococcus), legionella, nocardia
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What type of pathogen is implicated in infecting patients with an antibody deficiency?
|
Encapsulated bacteria. S. pneumonia, H. influenza
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What pathogens are implicated in infections during early neutropenia?
|
First 2 weeks. Pyogenic extracellular bacteria (S. aureus, GNR, pseudomonas), viruses (CA URI, HSV)
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What pathogens are implicated in infections during late neutropenia?
|
After 2 weeks. Pyogenic extracellular bacteria (S. aureus, GNR, pseudomonas), Fungi (candida, aspergillus)
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Name 4 main functions of the Embden-Meyerhof pathway
|
There is a net gain of 2 ATP. 2,3-BPG is generated which stabilizes the taunt, deoxygenated state of Hb increasing the O2 levels in the tissue (shifts curve to the right). Methemoglobin (Fe3+) is converted back to Hemoglobin (Fe2+) so O2 can bind again. G6PD is needed to protect RBCs from oxidative damage.
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What are Heinz bodies and in what cases are they found?
|
Heinz bodies are precipitated unstable Hb found in cases of hemolysis (oxidative damage, G6PD deficiency)
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What are the treatments for Thrombotic thrombocytopenic purpura and heparin-induced thrombocytopenia?
|
NO PLATELETS. For TTP, pheresis to remove clumps of platelets and vWF. For HIT, remove offending agent and anticoagulate
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What is necessary for a CML diagnosis?
|
The Philadelphia chromosome, Bcr-Abl, t(9:22)
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The Philadephia chromosome is common in what types of leukemia and which what sizes of the Bcr-Abl tyrosine kinase is implicated in each?
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ALL-190 kDa, CML- 210 kDa
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Describe the different phases of CML
|
Chronic phase: <5% blasts in the marrow
Accelerated phase: 6-19% blasts Blast crisis: 20% blasts (can be myeloid or lymphoid) |
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What is the treatment for CML and what are its side effects?
|
Imatinib (Gleevec) is a special Bcr-Abl tyrosine kinase inhibitor. Now Dasatinib and Nilotinib are used! Side effects include mild nausea / vomiting, periorbital edema, and pleural effusions
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How is CML in blast crisis treated?
|
Myeloid blast crisis is treated like AML, 7 cytarabine + 3 daunorubicin
Lymphoid blast crisis is a multi-agent regimen like de novo ALL |
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What does a CLL blood count look like?
|
There will be an elevated WBC with a differential that is primarily lymphocytic. In early stages, the Hb and platelet levels will be normal. In later stages, there is no room in marrow to escape and the Hb and platelet levels will be low.
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How is Chronic Lymphocytic Leukemia diagnosed?
|
No need for a bone marrow biopsy. Use peripheral blood for flow cytometry. Cells will exhibit B-cell markers (CD19, CD23, weak CD20, sIg K/L) with an abnormal T-cell marker (CD5)
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When is treatment for CLL indicated?
|
Patients need to be symptomatic with lymphadenopathy, splenomegaly, anemia or thrombocytopenia
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What immune defect is caused by Chronic Lymphocytic Leukemia?
|
Hypogammaglobulinemia making it difficult for patients to fight infection. Administer IVIg if the patient suffers from recurrent severe infections
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How is the immune system affected by Chronic Lymphocytic Leukemia?
|
Can be immune defficient (hypogammaglobulinemia) or have an over active immune system (Autoimmune hemolytic anemia, ITP)
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What is a concerning development of CLL, how is it diagnosed, and how is it treated?
|
Richter transformation is when one CLL clone becomes a diffuse large B-cell lymphoma. B-symptoms may be present, one abnormal area of lymphadenopathy, a PET scan reveals an active area, biopsy is necessary. Treat DLBCL with R-CHOP
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What is the treatment for CLL and what monitoring is important?
|
Purine analog based chemo (fludarabine, pentostatin). Patients are at high risk for tumor lysis, so hydrate and monitor closely
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|
How is Hairy Cell Leukemia diagnosed?
|
It a B-cell malignancy (CD19, CD20, CD22) with an abnormal T-cell marker (CD103). HCL is tartrate-resistant acid phosphatase (TRAP) positive.
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What does the bone marrow of a patient with Hairy Cell Leukemia look like?
|
Cells will look like fried eggs. Marrow will be fairly dry, with lots of fibrosis.
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|
What is Hairy Cell Leukemia treated with?
|
Purine analog (Cladribine)
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|
What type of karotype abnormalities are common in MDS as opposed to MPN?
|
MDS - mutations affect hematopoietic differentiation (mono/trisomies, deletions)
MPN - mutations affect proliferation (Bcr-Abl, RAS) |
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What is the general hematopoiesis of MPNs v MDS
|
MPN is highly effective, ordered hematopoiesis while MDS has ineffective, disordered hematopoiesis
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|
What are the general blood counts and organ involvement of MPNs v MDS?
|
In MPNs, the blood count is increased and there is organomegaly. With MDS, there will be a decrease in blood counts and no organomegaly
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|
What is the mechanism of alkylating agents?
|
Binds N7 guanine causing DNA mismatching, cross-linking, strand breaks, and ineffective DNA molecules
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|
What is a toxic byproduct of Ifosfamide, what does it cause, and how is this side effect combated?
|
Ifosfamide yields acrolein. When acrolein accumulates it binds to thiol in the bladder wall causing hemorrhagic cystis (hematuria, urinary frequency, irritation). Give with MESNA, which binds acrolein.
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|
What is the general indication for platinum analogues and what is its toxicity and side effect?
|
Platins are used in solid tumors (breast, lung, testicular, gyn, colorectal, bladder, lymphoma). Cisplatin is highly emetogeneic and nephrotoxic.
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|
What are the common toxicities of alkylating agents?
|
Myelosuppression, 2˚ leukemias, infertility, alopecia, nausea / vomiting
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|
Are camptothecins Topo I or II inhibitors?
|
Irinotecan and Topotecan are Topo I inhibitors
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|
Are anthracyclines Topo I or II inhibitors?
|
Rubicins are Topo II inhibitors
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|
Are epipodophyllotoxins Topo I or II inhibitors?
|
Etoposide and Teniposide are Topo II inhibitors
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|
What are the common toxicities of Topoisomerase inhibitors?
|
Myelosuppression, cardiotoxicity, extravasation injury, nausea / vomiting, red/orange urine
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|
What is given to prevent cardiotoxicity from anthracyclines?
|
Dexrazoxane inhibits iron-dependent free radical formation.
Liposomal doxorubicin isn't taken up as readily by cardiac tissue |
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|
What class of chemotherapy agents have drugs that can change urine color?
|
Topoisomerase inhibitors. Anthracyclines (red devils) turn urine red/orange. Mitoxantrone turns urine blue-green.
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|
What type of cancers are camptothecins indicated for?
|
Solid tumors (ovarian and cervical, lung, colorectal)
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|
What is the major side effect of irinotecan?
|
SEVERE diarrhea. "run to the can"
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|
What are some common clinical uses for methotrexate?
|
Osteosarcoma, ALL, NHL, CNS lymphomas, breast/bladder cancer
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|
What is the mechanism of methotrexate and what drug is necessary to give with it?
|
Methotrexate is a folate analog that blocks DNA synthesis. High does Methotrexate requires rescue doses of leucovorin which bypasses DHFR allowing DNA synthesis
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|
What are common methotrexate toxicities?
|
Nephrotoxicity, myelosuppression, GI toxicity, hepatotoxicity, neurotoxicity, dermatitis, death
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|
What is the mechanism, what are the indications, and toxicities for cytarabine?
|
Cytarabine is a cytosine analog that inhibits DNA polymerase. It is indicated in acute leukemias. It causes myelosuppression and at high doses causes nausea, CNS toxicity, and rash
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|
What is the main toxicity difference between Cytarabine and Gemcitabine?
|
Gemcitabine is not neurotoxic
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|
What is the mechanism of 5-fluorouracil and capecitabine?
|
5-FU and capecitabine are uracil analogs and they cause myelosuppression, bloody diarrhea, hand-foot syndrome, and mucositis.
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|
What are the indications and toxicities of Vinca Alkaloids?
|
VinBlastine, VinorelBine are for breast cancer and cause bone marrow suppression, anorexia, nausea / vomiting, diarrhea, alopecia
VinCristine are used in childhood leukemia and tumors and have CNS side effects. Vinca alkaloids also cause extravasation |
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|
What is the mechanism of taxanes?
|
The promote microtubule assembly and interfere with disassembly
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|
What are the indications for taxanes?
|
Gender tumors (Breast, ovarian, prostate), melanoma, NSCLC, head and neck cancers
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What are the toxicities of taxanes?
|
Myelosuppression, mucositis
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|
What drugs are indicated for multiple myeloma?
|
Vascular endothelial growth factor inhibitors. Bortezomib, then Carfilzomib if Bortezomib fails. Thalidomide and lenalidomide are also used.
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|
What is bleomycin indicated for and what is its major toxicity?
|
Testicular and Hodgkin lymphoma and it causes pulmonary fibrosis
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|
What is the mechanism, the two most common indications for hydroxyurea and what is its toxicity?
|
Hydroxyurea is a ribonucelotide reductase inhibitor. MPNs (CML, PV, ET), sickle cell disease. It causes myelosuppression.
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|
What pathway does Vismodegib inhibit and where is it indicated?
|
Inhibits the hedgehog pathway blocking proliferation of basal cell carcinoma
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|
What are the species origins of -omab, ximab, zumab, and umab?
|
-omab = mouse
-ximab = chimeric mouse/human -zumab = humanized -umab = human |
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|
What cluster of differentiation do rituximab, ofatumumab, and tositumomab work against?
|
CD20
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|
At what receptor do cetuximab and panitumumab have activity?
|
The epidermal growth factor receptor
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|
At what receptor do pertuzumab and trastuzumab have activity?
|
Human epidermal factor (HER-2)
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|
Where does alemtuzumab act and what is its indication?
|
Alemtuzumab acts on CD52 of B and T-cells and is a 2nd or 3rd lin CLL drug
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|
Where does rituximab act and what is its indication?
|
CD20 on B-cells and it is indicated for NHL and CLL
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|
Where does ibritumomab and tositumomab act and what is their indication?
|
Ibritumomab and tositumomab bind CD20 and are radioactive so they deliver local radiation. They are indicated as 3rd line treatment in follicular lymphoma. They are mouse derived and the patient will develop antibodies so they can only be given once.
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|
Where does ofatumumab act and what is its indication?
|
CD20 on B-cells. It is a 2nd or 3rd line treatment for CLL
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|
Where does brentuximab vedotin act and what is its indication?
|
CD30 with a mitotic inhibitor conjugate is used in Hodgkin and large cell lymphomas
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|
What receptor is a prime target for breast cancer drugs and what are the 1st and 2nd line treatments?
|
HER-2. Trastuzumab and Pertuzumab, then Lapatanib
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|
Where do Cetuximab and Panitumumab have their action and what are they indicated for?
|
HER-1/EGFR. Colorectal cancer
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|
Where do Erlotinib and Gefitinib have their action and what are they indicated for?
|
HER-1/EGFR. Non-small cell lung cancer. Erlotinib is 2nd line and Gefitinib is 3rd line
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|
Where does Vandetanib act and what is it indicated for?
|
A number of different receptors (VEGF, EGFR) and it is the 1st line therapy for medullary thyroid cancer
|
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|
What is the common toxicity for monoclonal antibodies?
|
Infusion reaction (SOB, fever, chills, nausea, asthenia, headache)
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|
What is Bevacizumabs mechanism of action, what are its indications, and what are its side effects?
|
Bevacizumab is a VEGF antagonist and decreases angiogenesis. It is indicated in metastatic solid tumors and can lead to thrombolitic bleeding events and headaches
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|
What is the mechanism of action for Temsirolimus and Everolimus and where is their indication?
|
mTOR antagonist, blocking cell growth, proliferation, angiogenesis, and metabolism. It is indicated in advanced renal cell carcinoma
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|
Where does ruxolitinib act and what is its indication?
|
Inhibits a mutated JAK-2 and is indicated in chronic myelofibrosis
|
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|
What two receptors do Vemurafenib and Ipilimumab act upon and what are they used to treat?
|
BRAF (Vemurafenib) and CTLA-4 (Ipilimumab) and they are used to treat melanomas
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|
What malignancy is treated with Sipuleucel-t and what are its side effects?
|
Castrate-resistant prostate cancer. It can cause an infusion reaction and fatigue
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|
|
How do lymphocyte enter lymph nodes?
|
Through high endothelial venules and afferent lymphatics
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|
|
What cell can be distinguished by its clock face appearance?
|
Plasma cells
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|
|
Where in the spleen are T-cell found?
|
In periarterial lymphatic sheaths in the white pulp
|
|
|
What are 5 different pathologies that Parvovirus B19 can cause?
|
Hydrops fetalis, fifths disease, aplastic crisis in chronic hemolytic anemia, seronegative RA, chronic hemolytic of immunocompromise
|
|
|
What are the most common causes of pneumonia in the immunocompromised host?
|
CMV, VZV, HSV, community acquired (RSV, influenza, parainfluenza)
|
|
|
What are the early and late immune deficits in allogeneic BMT patients?
|
Patients are neutropenic early and then have cell-mediated deficits (low T-cells)
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|
What is used to treat (or prevent) CMV infection with allogeneic BMT patients?
|
Check for seropositivity. Ganciclovir or valganciclovir.
|
|
|
What are the two things to know about radiation oncology?
|
It is a multi-disciplinary specialty, with many different people working together on the same case, and it is a local treatment that causes local side effects
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|
How do chemo drugs cause nausea / vomiting?
|
They centrally activate the chemo trigger zone which releases neurotransmitters that activate the brainstems vomiting center. Peripherally they irritate the GI mucosa, releasing neurotransmitters that activate the vomit center.
|
|
|
What is the treatment for acute chemo-induced nausea / vomiting?
|
Day 1: Ondansetron (5HT3 antagonist) + Dexamethasone +Aprepitant (NK-1 antagonist)
Day 2/3: Dexamethasone +Aprepitant |
|
|
What is used to treat delayed chemo-induced nausea / vomiting?
|
Neurokinin-1 antagonist with 5HT3 antagonist and a steroid
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|
|
What can be used to rescue patients from chemo-induced nausea / vomiting?
|
Metoclopramide (dopamine antagonist), dronabinol (cannabinoid), phenothiazines (prochlorperazine / promethazine - dopamine antagonists)
|
|
|
What does filgrastim do?
|
Filgrastim stimulates neutrophil proliferation and can increase the circulation of blood stem cells (for transplant harvest)
|
|
|
What does sargramostim do?
|
Stimulate neutrophil, macrophage, monocyte, and eosinophil production
|
|
|
When are ESAs indicated?
|
Erythropoietin stimulating agents are indicated for terminal patients to increase quality of life
|
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|
What do Oprelvekin, Romiplastim, and Eltrombopag do?
|
Stimulate thrombopoiesis
|
|
|
Where in the lymphatic system are plasm cells found?
|
In the medulla of the lymph nodes
|
|
|
Where do T-cells produced by alpha or beta genes circulate?
|
In the thymus
|
|
|
Where do T-cells produced by delta or gamma genes circulate?
|
In the epithelium of the pulmonary and GI tracts
|
|
|
What is the phenotype and genotype presentation of follicular lymphoma?
|
Small cleaved, mature-appearing cells, can have a raisin appearance. B-cell lineage: CD20+, CD10+, bcl-2+, CD5-. Centroblasts are proliferating and growing out of proportion
|
|
|
What genetic finding is common in follicular lymphoma?
|
t(14:18) IgH:bcl-2
|
|
|
What is the phenotype and genotype presentation of diffuse large B-cell lymphoma?
|
Large lymphocytes. B-cell lineage: CD19+, CD20+
|
|
|
What is the standard treatment for diffuse large B-cell lymphoma?
|
R-CHOP. Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone
|
|
|
What viruses are associated with Burkitt's Lymphoma?
|
EBV & HIV
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What blood malignancies are EBV associated with?
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Burkitt's and Hodgkin lymphoma
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What is the phenotype and genotype presentation of Burkitt's lymphoma?
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Tissue will exhibit a starry sky pattern (histiocytes). CD20+, CD10+, CD5-. Cytogenetic abnormality with chromosome 8, c-MYC. t(8:14), t(2:8), t(8:22)
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What are Burkitt's lymphoma patients at a very high risk for?
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Tumor lysis syndrome
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What translocation is associated with Burkitt's Lymphoma?
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t(8:14) MYC:IgH
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What malignancies are associated with a t(8:14) translocation?
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MYC:IgH. Burkitt's lymphoma, DLBCL
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What is the most common type of Hodgkin Lymphoma?
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Nodular sclerosis Classical Hodgkin Lymphoma
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What phenotype is associated with B-cell LBL?
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TdT+, CD20-, sIg-
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What are common genotype associated with B-cell LBL and are the favorable or unfavorable?
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Unfavorable: t(9:22) Bcr-Abl, t(4:11) MLL, hypodiploidy
Favorable: Hyperdiploidy, t(12:21) TEL/AML-1 |
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What phenotype is associated with T-cell LBL?
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TdT+, CD4/8 co-expression
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What malignancy are "smudge cells" associated with?
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Chronic Lymphocytic Leukemia
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What malignancy are "soccer ball" cells associated with?
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Clumpy chromatin of small lymphocytic lymphoma
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What phenotype is associated with CLL/SLL?
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B-cell lineage: CD19+, CD20+, dim sIg, CD5+ (abnormal T-cell marker)
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What translocation is associated with Follicular lymphoma?
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t(14:18) bcl-2:IgH
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What translocation is associated with mantle cell lymphoma?
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t(11:14)
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Which lineage of lymphomas present cutaneously and name 2.
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T-cell NHL (Mycosis fungoides, Anaplastic large cell lymphoma)
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What are smudge cells?
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Fragile abnormal B-cells from CLL that break and smear when put on a blood smear
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What is the phenotype and genotype found in CLL/SLL?
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B-cell lineage: CD19+, CD20+, dim sIg, CD5+ (T-cell marker). del 13q14 or trisomy 12.
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What phenotype and genotype is found in anaplastic large cell lymphoma? How does this expression aid treatment?
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T-cell lineage: CD3+, CD4+, strong CD30+, ALK-1. TCR rearrangement t(2:5) ALK/NPM. The presence of ALK allows a targeted chemo Crizotinib to be used
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What cell is characteristic of Hodgkin Lymphoma and what are it's phenotypic markers?
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Reed-Sternberg cell is of B-cell lineage. CD15+, CD30+, EBV+
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What are Bence Jones Proteins? Where will they be found and what organ are they toxic to?
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Monoclonal light chain immunoglobulins that are secreted in the urine and are toxic to the renal tubules
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What is the phenotypic and genotypic pattern seen in multiple myeloma?
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No B-cell markers. CD38+, CD138+. Clonal Ig rearrangement
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What are the common presentation of the two types of Burkitt lymphoma?
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African: head, neck, jaw masses
Endemic: rapidly expanding abdominal mass arising from ileocecal GI structure (intussusception common) |
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What is the treatment for Burkitt lymphoma?
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CNS prophylaxis, intrathecal methotrexate, craniospinal radiation
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What is the phenotype seen in Mycosis Fungoides?
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T-cell lineage: CD4+, CD7-
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How does the epidemiology differ among the different types of Hodgkin's Lymphoma?
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Nodular sclerosis: Mediastinal involvement. Females
Mixed cellularity: >55yo Lymphocyte rich: uncommon, young males Lymphocyte depleted: HIV/AIDS |
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What do vHL and HIF-1a do?
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In normoxic conditions, vHL protein ubiquitinates HIF-1a for proteosome degradation. Without HIF-1a, there is no HIF-1a/HIF-1b complex, which is needed for EPO transcription to be upregulated by the kidney. In hypoxic conditions, HIF-1a is not degraded, it complexes with HIF-1b and binds to and upregulates the transcription of EPO
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What is the relevant mutation in polycythemia vera and what are the resulting lab abnormalities?
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JAK-2 is constitutively active, releasing RBC production from EPO control. Lots of RBCs mean that there is no need for more EPO. EPO levels will be low, with elevated Hb, Hct, platelets, WBCs, and general bone marrow hypercellularity
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What are the signs/symptoms and treatment of Polycythemia vera?
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"Congestion": headaches, visual changes, dizziness, parasthesia, facial plethora. Warm pruritis, bleeding, bruising, thrombosis (MI, DVT, PE, CVA), hepatosplenomegaly, erythromelalgia. Phlebotomy, hydroxyurea, aspirin.
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What is the relevant mutation in essential thrombocytosis and what are the resulting lab abnormalities?
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Jak-2 mutation releases thrombopoiesis from TPO control. TPO levels will be normal of elevated, due to decreased absorption, WBC and Hb will be normal.
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What are the symptoms and treatment of Essential Thrombocytosis?
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Bleeding, thrombosis (CVA, TIA, MI), splenomegaly, erythromelalgia. Hydroxyurea and aspirin
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What treatment is used to treat chronic eosinophilic leukemia?
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Imatinib (Gleevec)
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What is the clinical presentation of chronic myelofibrosis?
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Hepatosplenomegaly, extramedullary hematopoiesis (pleural/pericardial effusion, ascites, CNS)
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What cells are associated with chronic myelofibrosis?
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Pseudo-Pelger-Huet cells, giant platelets
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What CBC and bone marrow findings do you get with patients with chronic myelofibrosis?
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Anemia, WBC and platelets cna be high or low, depending on the progression of the disease. Marrow will have decreased cellularity (dry taps) with reticulin and collagen fibrosis
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What is the treatment for chronic myelofibrosis?
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Palliative therapy: Ruxolitinib, Hydroxyurea, splenectomy, appropriate acute leukemia treatments if it transforms
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What are the common pathway, presentation, and treatment for myeloproliferative disorders?
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JAK-2 is mutated, leading to increased proliferation and splenomegaly. They are treated with hydroxyurea
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What diagnoses are on the spectrum of plasma cell dyscrasias and how do they differ?
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Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, and Plasma Cell Leukemia increase in number of plasma cells and proteins produced
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How are plasma cell dyscrasias diagnosed?
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Bone marrow biopsy and aspirate to measure number of plasma cells. Test to measure amount of protein (antibody): CMP, Serum quantitative immunoglobulins, serum protein electrophoresis, serum free light chains.
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Where are common sites of end organ damage in plasma cell dyscrasias?
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Lytic bone lesions: Calvarium, spine, ribs, pelvis, long bones.
Kidney damage occurs from infiltrating plasma cells and immunoglobin deposits. Bone marrow shows marked increase in plasma cells, causing a normochromic, normocytic anemia with circulating plasma cells. Sticky proteins lead to Rouleaux cells. Electrolytes: Increased bone reabsorption increases Ca, which contributes to renal dysfunction and stones, bones, moans, groans |
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How do we get stem cells in the peripheral blood for collection?
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Filgrastim, a G-CSF that promotes circulation of hematopoietic stem cells
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What are the most common indications for allogeneic transplants?
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Multiple myeloma, NHL, AML, HL
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What are the most common indications for autologous transplants?
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Multiple myeloma, NHL, HL, other cancers
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Why are autologous transplants beneficial?
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Allows for higher, stronger, more aggressive doses of chemo, while "rescuing" the patient from myelosuppression
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What are the relative 3 month transplant related mortatlity for autologous v allogenic transplants?
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Autologous <5%
Allogeneic 10-20% |
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What are 3 keys to a successful autologous BMT?
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Have a chemosensitive drug and be able to harvest a healthy graft (no contamination in graft, no bone marrow failure)
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What are 3 benefits of an allogeneic BMT?
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You are guaranteed a clean graft, it can be used in bone marrow failure disease, it is an INTERVENTION due to the graft v tumor effect.
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What is ideally matched to avoid GvHD?
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6/6 HLA matches (A,B,D)
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What are benefits of using umbilical cord blood in allogeneic BMT?
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Cells are relatively immune incompetent so less GvHD, donors can tolerate a wider HLA disparity, donor is less likely to be CMV+, more common for ethnic minorities
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What is the frequency of occurrence of GvHD in allogeneic BMT patients and what are some risk factors?
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10-50% of allogeneic BMT recipients will get GvHD. Increasing HLA disparity, gender disparity, CMV disparity, location of BM harvest, prophylactic regimen used
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Where and how does GvHD most commonly present?
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Cutaneously as an erythematous maculopapular rash with bullae beginning at the time of engraftment. If GvHD becomes chronic, sclerodermatous changes are seen
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Where are the three most common sites of manifestation for GvHD?
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Skin - erythematous maculopapular rash with bullae
Liver - increasing conjugated bilirubin and alkaline phosphatase, due to bile canaliculi damage GI tract - severe diarrhea, cramping |
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What is given to prevent GvHD?
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T-cell depletion: Alemtuzumab (liquid AIDS, binds CD52)
Pharmacology: Methotrexate, cyclosporine, steroids |
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What is given to treat GvHD?
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Add on immunosuppression: pulse dose steroids
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What are some host requirements for BMTs?
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Minimal disease state, preserved cardiac and liver function, no active infection
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What are the current age guidelines for hematopoietic stem cell transplants?
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Autologous up to 70 years of age.
Allogeneic up to 65 years of age. |
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How does chronic disease lead to anemia in the elderly?
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Chronic inflammation releases cytokines (IFN, TNF, IL-1, IL-6, IL-10) that act in 4 ways.
- Promotes hepcidin from the liver, decreasing serum Fe - Decreases EPO production and release by the kidneys, decreasing RBC count - Increases macrophage phagocytosis of RBCs - Inhibits erytropoiesis in the bone marrow |
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What is the general progression of anemia morbidity in older adults?
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Anemia increases cardiac disease (MI, CHF), which decreases muscle mass and strength, which increases disability and prevalence of falls and fractures. Anemia is also associated with cognitive impairment
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Why are some general causes for increasing malignancy with older adults?
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Longer carcinogen exposure, decreased DNA repair ability, increased genomic instability, decreased tumor suppression and immune surveillance
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What are some age related changes that affect pharmacological treatments?
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Decreased intestinal absorption can change bioavailability.
Declines in renal excretion can increase toxicity. Changes in volume of distribution increases toxicity from free drug Altered cytochrome p450 metabolism impairing activation or elimination |
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What are the two possible cofactors for Factor VIIa activity and in what circumstances do they occur?
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Factor X if it is a static system (already some clotting/stasis)
Factor IX if it is a flowing system |
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What are the functions of thrombin?
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It catalyzes fibrinogen into fibrin, activates Factor XIII (which cross-links fibrin to g and then a), activates Factors V and VIII which accelerate the generation of thrombin. Excess thrombin is also used to activate Protein C with the help of Thrombomodulin.
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What are 4 general mechanisms that can throw off the thrombin/plasmin ratio?
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Severe deficiency of a single factor (Hemophilia, Immune inhibitors), Combined deficiency of many factors (Vitamin K deficiency, Liver disease), Anticoagulation (Warfarin, Heparin), Excess fibrinolysis (Liver disease, Thrombolytic therapy)
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Based on hydraulic forces, is there more bleeding from arteries or veins?
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Arteries, there is a larger internal/external pressure gradient difference
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What is the mechanism responsible for a tamponade?
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If the external pressure exceeds the mean arterial pressure, blood flow will stop, also called "compartment syndrome"
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What is Virchow's triad and what pathology does it describe?
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The environment necessary for venous thrombosis. Alteration in the vessel (damaged endothelium), alteration in the blood (increased thrombin, decreased plasmin), stasis (valve pockets or areas of hyposia)
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What are some thrombophilic risk factors?
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Age, lupus anticoagulant, DIC, obesity, sedentary lifestyle, smoking, malignancy, surgery, pregnancy, HIT/HITT
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How can you control Stage 1 DIC
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Give low dose heparin to amplify AT3 effectiveness and shut down thrombin generation. GPIIb/IIIa inhibitors to block platelet aggregation. ASA, Clopidogrel (plavix) to block platelet activation.
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What necessary coagulation factors are deficient in stage 2 DIC?
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Factors V and VIII and AT3 have been depleted
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What treatment, in what order, is required for DIC?
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Give coagulation factors (platelets, AT3, prothrombin, cryoprecipitate), then heparin to inhibit thrombin, and finally AMICAR to inhibit plasmin
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How do primary hemostasis defects present differently than plasma coagulation defects?
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Primary hemostasis defects or platelet problems present as oozy-bruisy bleeding, while a defect in plasma coagulation will produce a hemorrhagic gushing bleed.
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Differentiate the inheritance of Hemophilia A, Hemophilia B, and vWD
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Hemophilia A & B are X-linked. vWD is autosomal dominant
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Why are both primary and secondary hemostasis defective in vWD?
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vWF is involved in primary hemostasis by adhering platelets to the damaged endothelial cells and aggregating platelets together and in secondary hemostasis by being a chaperone for Factor VIII, extending it's half-life. vWD decreases platelet adhesion and aggregation AND decreases thrombin formation via Factor Va upregulation
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What variation of Hemophilia is most common?
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Factor VII (Hemophilia A, Classical) is most common, 85%
Factor IX (Hemophilia B, Christmas Disease) is only 10% |
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On what chromosome is the gene for Hemophilia located?
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The X chromosome
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What are the most common genetic mutations that cause Hemophilia?
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Point mutations or an inversion of intron 22
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Where are when are common bleeds in hemophilics?
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Bleeds into target joints (hips, ankles, knees, wrists), deep muscles (psoas), or intracranially. That occur post-surgery, trauma, or dental extraction
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How do you determine the severity of a patient's Hemophilia?
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Measure their % of Factor compared to normal. <1% is severe (childhood, spontaneous), 1-5% is moderate (post minor trauma, maybe spontaneous), 5-20% is mild (post-trauma or surgery).
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What are side effects of a hemophilic patient bleeding into joints?
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With inadequate treatment, arthritis, decreased ROM, synovitis, joint destruction
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Where are common site for soft tissue bleeds in hemophiliacs and what is a severe consequence of those bleeds?
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Face, palms, calves, thigh or groin. In enclosed spaces, this bleed can lead to compartment syndrome
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What is given to prophylacticly treat hemophiliacs?
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Recombinant factor of whichever factor they are missing
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What is DDAVP and what is it used to treat?
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A vasopressant that causes vWF to be released from the endothelial cells, increasing clotting ability of hemophiliac patients with some Factor VIII (vWF-FVIII complex)
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What is a complication of treating Hemophilia patients with recombinant factor?
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Factor VIII deficient patients can develop alloantibodies to the factor, since their body doesn't recognize it. This happens less frequently with Factor IX
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Who is at risk for an acquired hemophilia?
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Older adults, postpartum, underlying autoimmune disorder (lupus, RA). They can develop antibodies to Factor VIII.
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What are two ways to treat vWD?
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DDAVP, release of VWF. Humate P, pure Factor VIII containing Factor VIII and vWF
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What protein is the target in ITP?
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The body makes antibodies against GPIIb/IIIa, tagging platelets for removal via the spleen.
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What will the PT and aPTT results look like in ITP?
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Normal. It is a platelet degradation problem, nothing is wrong with the coagulation cascade
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What are normal aPTT and PT times?
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aPTT = 21-35 seconds
PT = 10-14 seconds |
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Vitamin K deficiency can be identified using what coagulation test?
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Prothrombin Time, which is sensitive to VII, X, V, II, fibrinogen. (X, V, VII, II are vitamin K coag factors)
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What is the difference between what a traditional FDP assay and a D-dimer test are measuring?
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FDP doesn't distinguish between plasmin cleaving fibrinogen and fibrin and so it can be elevated even if there is no clot present. D-dimer only measures cross-linked fibrin degradation, from clots
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What would the PT, aPTT, and platelet levels be in DIC?
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PT will be increased. PTT will be increased. Platelets will be low.
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What would the PT, aPTT, and platelet levels be in TTP?
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PT will be normal. PTT will be normal. Platelets will be low.
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What would the PT, aPTT, and platelet levels be in HUS?
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PT will be normal. PTT will be normal. Platelets will be low.
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What would the PT, aPTT, and platelet levels be in liver disease?
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PT will be high. PTT will be high. Platelets will be normal.
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What are some disorders / risk factors for DIC?
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Malignancy, obstetric emergency, organ destruction, sepsis, severe toxic reactions (drugs, transfusion reactions), trauma, vascular abnormality
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What is the clinical pentad for Thrombotic thrombocytopenic purpura?
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FAT-RN: Fever, anemia, thrombocytopenia, renal dysfunction, neurologic defects
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What is the mechanism of HUS?
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Hemolytic Uremic Sydrome. E.coli 0157:H7 causes an infectious gastroenteritis where it is absorbed by the GI endothelia, releases Shiga-like toxin, and activates platelets. Causes a consumptive thrombocytopenia
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What coagulation factors are dependent on Vitamin K?
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Proteins C/S, Factors II, VII, IX, X
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What is an APC Mix used to diagnose?
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Factor V Leiden deficiency. A point mutation in Factor V renders it resistant to proteolysis by Protein C
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What are risk factors for thrombi?
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Bed rest, MI, Malignancy, A.fib, Sickle Cell
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What are some acquired risk factors for venous thrombus?
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Surgery, trauma, medical illness, immobilization, pregnancy, contraception, indwelling cather, malignancy, air travel
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What anticoagulant is recommended for cancer patients?
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Dalteparin or Enoxaparin for at least 6 months
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What medications are indicated to treat heparin-induced thrombocytopenia and where are their actions?
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Bivalirudin, Argatroban - direct thrombin inhibitor
Fondaparinux - Factor Xa inhibitor |
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What are the 4 T's and diagnostic test associated with HIT?
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Serotonin release assay.
Thrombocytopenia %, Timing of fall (compared to heparin dose), Thrombosis increase, no oTher causes |
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What is the reversal agent of Enoxaparin?
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Protamine sulfate
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What is the reversal agent of Dalteparin?
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Protamine sulfate
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What is the reversal agent of warfarin?
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Vitamin K
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Are heparins indicated in VTE prophylaxis, treatment, or both?
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Both
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What is the therapeutic INR range?
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2-3
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What are some factors that interfere with warfarin dosing?
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Cyp2C9 inhibitors or inducers (Fluconazole, rifampin), chemos (capecitabine [5-FU], Aprepitant [nk-1]), contraceptives, leafy green vegetables, cereal, lamb
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What are side effects of warfarin?
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Bleeding (reverse with Vitamin K), necrosis, vasculitis
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What is an important drug interaction of argatroban?
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It can produce an artifically high INR, affecting co-administration with warfarin
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Is warfarin indicated in VTE prevention, treatment, or both?
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VTE treatment
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Are direct thrombin inhibitors indicated in VTE prevention, treatment, or both?
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VTE prevention
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Are Factor Xa inhibitors indicated in VTE prevention, treatment, or both?
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Both
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What types of analgesics are indicated for mild to moderate pain?
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Non-opioids. Aspirin, NSAIDs
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What types of analgesics are indicated for moderate to severe pain?
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Mild opioids (codeine) with or without non-opioids
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What types of analgesics are indicated for severe pain?
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Strong opioids (morphine) with or without non-opioids
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What is the mechanism of acetaminophen?
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Blocks prostaglandins via the COX-3 receptor
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What is the maximum daily dose of acetaminophen?
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4 grams for adults
2 grams for older adults |
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What is a concern when you give acetaminophen to oncology patients?
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Acetaminophen masks fever, an important signal in immunocompromised patients
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Where does Celecoxib have it mechanism of action?
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COX-2 inhibitor. No GI insult
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What is the main side effect seen with opioids and how is it handled?
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Constipation. Give stool softener AND a stimulant laxative prophylactically. Treat with methylnaltrexone (acts quickly)
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What are the common side effects of opioids?
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Sedation, nausea, vomiting, CONSTIPATION, euphoria/ dysphoria
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Which analgesics are best used to treat neuropathies caused by chemotherapies?
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Anti-convulsants/ depressants: Gabapentin, venlafaxine, duloxetine
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