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112 Cards in this Set
- Front
- Back
What test can be used to diagnose B-thalassemia minor?
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Hemoglobin electrophoresis.
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You see hypersegmented neutrophils on a peripheral blood smear. What are you thinking?
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Megaloblastic anemia.
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What is one cause of megaloblastic anemia that doesn't respond to Vit B12 and folate supplementation?
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Orotic aciduria.
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A bone marrow biopsy shows hypocellularity with fatty infiltration. What's the dx? What causes this?
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Aplastic anemia; radiation and drugs, viral agents, Fanconi's anemia, idiopathic.
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A patient is diagnosed with macrocytic, megaloblastic anemia. What is the danger of giving folate alone?
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Correct anemia, but not address B12 def --> pt could get peripheral neuropathy w/o anemia --> you're going to be like "WTF".
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A patient with sickle cell disease develops osteomyelitis. What is the offending organism?
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Salmonella.
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What is the difference between the hemoglobin S and hemoglobin C defect?
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HbC: glutamic acid-to-lysine mutation at position 6 in β chain.
HbS: glutamic acid-to-valine mutation at position 6 in β chain |
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What enzyme does Warfarin inhibit?
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Epoxide reductase. No activation of Vitamin K for gamma-carboxylation of glutamate residues on immature clotting factors.
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Which clotting factor is deficient in Hemophelia A? Hemophelia B?
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Factor VIII; Factor IX.
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Why are neonates given a shot of Vit K after birth?
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They lack the enteric bacteria needed to produce Vit K.
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What are the effects of bradykinin on the body?
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Increased vasodilation, increased permeability, and increased pain.
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What clotting factors are dependent on Vitamin K for synthesis?
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Factors II, VII, IX, X, Protein C, Protein S.
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What is the function of Proteins C and S? What is the clinical consequence of a deficiency in Protein C and/or S?
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Proteins C and S inactivate Va and VIIIa; Hypercoaguable state.
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What is the defect in Bernard-Soulier disease?
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Defect in platelets! Decreased Gp1b on platelets = decreased adherence to vWF on endothelial collagen --> no platelet to collagen adhesion.
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What is the defect in Glanzmann's thrombasthenia?
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Defect in platelets! Decreased GpIIb/IIIa = no platelet to platelet aggregation!
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What is the defect in Idiopathic Thrombocytopenic Pupura (ITP)? What might you see on a blood smear?
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Poor platelet survival! Anti-GpIIa/IIIb antibodies --> peripheral platelet destruction! Increased megakaryocytes on blood smear.
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What is the defect in Thrombotic Thrombocytopenic Purpura (TTP)?
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Poor platelet survival! Deficiency in ADAMTS 13 = decreased degradation of vWF multimers = increased platelet aggregation and thrombosis.
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What's the defect in vonWillebrand's disease?
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Decreased vWF = defect in platelet-to-collagen adhesion. MOST COMMON INHERITED BLEEDING DISORDER.
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What can cause DIC? What will you see in the labs?
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"STOP Making New Thrombi": Sepsis (gram-negative), trauma, obstetric complications, acute pancreatitis, malignancy, nephrotic syndrome, transfusion; Increased fibrin split products (D-dimers), decreased fibrinogen, decreased factors V and VIII.
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What are the hereditary thrombosis syndromes leading to hypercoaguability?
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Factor V Leiden, Prothrombin gene mutation, antithrombin deficiency, protein C or S deficiency.
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What's the defect in Factor V Leiden?
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Mutant Factor V cannot be degraded by Protein C. MOST COMMON CAUSE OF INHERITED HYPERCOAGUABILITY.
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What are the treatments for overdose of heparin and warfarin?
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Protamine sulfate for heparin OD and Vit K +/- FFP for warfarin OD.
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What lab value is used to monitor heparin? warfarin? enoxaparin?
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PTT; PT/INR; Xa.
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What is the MOA for heparin?
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Supercharges antithrombin! Decreases the action of IIa (thrombin) and Xa.
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What is the benefit of LMW heparins like enoxaparin?
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Increased bioavailability, no need to monitor PTT, longer half-life, can be admin SC, acts more on Xa.
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What is the treatment for heparin-induce thrombocytopenia (HIT)?
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Lepirudin, bivalirudin --> directly inhibit thrombin.
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You have to anticoagulate a pregnant woman. Which drug will you give her?
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Heparin, b/c it doesn't cross the placenta like warfarin.
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What are the thrombolytics? What is their MOA?
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Streptokinase, urokinase, tPA (alteplase), and APSAC (anistreplase); Directly or indirectly aid in converting plasminogen --> plasmin, which cleaves thrombin and fibrin clots.
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When would you use thrombolytics?
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EARLY MI, EARLY ischemic stroke.
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How do you treat a thrombolytic toxicity?
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Aminocaproic acid.
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Where does fetal erythropoiesis take place?
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Yolk sac (wks 3-8) --> Liver (wks 6-30) --> spleen (wks 9-28) --> bone marrow (wks 28+).
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Where does adult erythropoiesis take place?
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Long bones, pelvis, sternum, ribs, cranial bones, vertebrae.
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How are the γ chains of fetal hemoglobin different from the β chains of adult hemoglobin?
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Decreased affinity for 2,3 BPG and increased affinity for O2.
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What is the average lifespan of an erythrocyte? What gives the erythrocyte its characteristic biconcave shape and flexibility? What is the main energy source for the erythrocyte?
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120 days; Spectrin! Glucose (it's the ONLY energy source!).
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You see a teardrop cell on a blood smear. What do you think?
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Bone marrow infiltration (e.g., myelofibrosis).
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You see target cells on a peripheral blood smear. What do you think?
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"'HALT' said the hunter to his TARGET": HbC disease, asplenia, liver disease, thalassemia.
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You see Howell-Jolly bodies on peripheral blood smear. What do you think?
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Patient with functional hyposplenia or asplenia (e.g., sickle cell disease or splenic trauma).
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You see basophillic stippling on a peripheral blood smear. What do you think?
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"BASte the ox TAIL": Thalassemias, anemia of chronic disease, iron deficiency, lead poisoning.
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You see schistocytes/helmet cells on a peripheral blood smear. What do you think?
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DIC, TTP/HUS, traumatic hemolysis.
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What is the rate-limiting enzyme in heme synthesis?
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ALA-synthase.
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What enzyme is affected in lead poisoning? What substrate accumulates?
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ALA-dehydratase and Ferrochelatase; Protoporphyrin accumulates.
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What are the sx of lead poisoning?
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Lead lines on gingivae and epiphyses of long bones, encephalopathy and erythrocyte basophillic stippling, abd colic, sideroblastic anemia, wrist and foot drop.
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How do you treat lead poisoning?
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Adults: EDTA, Dimercaprol.
Children: Succimer, Dimercaprol. |
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What enzyme is affected in acute intermittent porphyria? Which substrate accumulates? What are the clinical sx?
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Porphobilinogen deaminase; Porphobilinogen, ALA accumulate; Sx include RED-WINE COLORED URINE, polyneuropathy, psych problems, acute abd, precipitated by drugs.
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What are the features of porphyria cutanea tarda? What enzyme is affected? What substrate accumulates?
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Blistering cutaneous photosensitivity, TEA-COLORED URINE; nuked uroporphyrinogen decarboxylase, uroporphyrin accumulates.
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What are the main type of microcytic anemia?
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Iron-deficiency, ACD, thalassemias, lead poisoning, and sideroblastic anemia.
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What syndrome is associated with iron-deficiency anemia? What are the histological findings?
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Plummer-Vinson syndrome (ID anemia, atrophic glossitis, esophageal web); Hypochromia, microcytosis seen under the microscope.
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What are some of the causes of iron-deficiency anemia?
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Chronic blood loss (GI or menorrhagia), malnutrition/absorption disorders, increased demand (pregnancy). R/O COLON CANCER!
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What type of mutation is present in β-thalassemia? What does it result in? In which populations is this mutation prevalent?
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Point mutation in splice sites and promotor sequences --> decreased β-globin synthesis; Mediterranean populations.
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What test can be done to diagnose β-thalassemia minor? What would be considered a "positive" result.
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Hb electrophoresis; HbA2 > 3.5%.
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What type of hemoglobin is increased in both β-thalassemia major and minor?
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HbF (α2γ2).
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In which populations is α-thalassemia prevalent? What does a 4 gene deletion result in? 3 gene deletion? 1-2 gene deletion?
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Asian and African populations; 4 gene deletion = γ4, incompatible with life (causes hydrops fetalis); 3 gene deletion = HbH disease (β4); 1-2 gene deletion results in no significant anemia.
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Which enzymes does lead inhibit? What is the genetic disease with the same pathogenesis?
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Ferrochelatase and ALA dehydratase --> inhibits heme synthesis; Sideroblastic Anemia --> defect in the ALA gene --> defect in heme synthesis --> ringed sideroblasts in the bone marrow!
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What is the cause of megaloblastic anemia with peripheral neuropathy? What bug might cause this? What are other possible causes?
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B12 deficiency; Diphyllobothrium latum; malabsorption (Crohn's), strict vegan diet, pernicious anemia.
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What type of anemia is commonly seen in alcoholics?
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Megaloblastic anemia caused by Folate deficiency.
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What could be the cause of a megaloblastic anemia in an HIV+ patient?
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Zidovudine.
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What would cause a megaloblastic anemia refractive to tx w/Vit B12 and folate, but that is reversible with Vit B6?
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Orotic aciduria.
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What type of labs would you see with ACD?
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Decreased Iron, Decreased TIBC (it's just not being used), Increased Ferritin.
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What is the mutation responsible for Sickle Cell Hb (HbS)? What is the mutation responsible for HbC?
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Glutamate --> Valine in β chain.
Glutamate --> Lysine in β chain. |
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What disease has a characteristic "crew cut" appearance on x-ray?
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Sickle cell anemia.
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What is the defect in hereditary spherocytosis? What are the findings? Tx?
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Defect is in ankyrin or spectrin -- loss of characteristic discoid shape to RBC --> premature removal of RBCs by spleen; splenomegaly, jaundice, pigmented gallstones!, aplastic crisis (if infected with B19), Howell-Jolly bodies after splenectomy; Tx is splenectomy
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What is the defect in pyruvate kinase deficiency anemia?
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Defect in pyruvate kinase --> decreased ATP --> rigid RBCs --> hemolytic anemia in the newborn.
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Impaired synthesis of what molecule is responsible for paroxysmal nocturnal hemoglobinuria?
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CD55 or CD59 (GPI anchor/decay-accelerating factor in RBC membrane) --> prevents complement-mediated RBC lysis!
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What types of complications are seen in patients with HbSS?
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Aplastic crisis, autosplenectomy, increased risk of infection with encapsulated bugs, SALMONELLA OSTEOMYELITIS, painful crisis, renal papillary necrosis.
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What are the findings of extravascular hemolysis?
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Macrophages in spleen clear the RBCs: increased LDH, increased UCB --> jaundice.
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What are the features of intrinsic hemolysis?
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Decreased haptoglobin, increased LDH, hemoglobinuria.
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What type of Ig is involved in warm agglutinin AIHA? Cold agglutinin AIHA?
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IgG; IgM.
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What is an example of a potentially deadly warm agglutinin AIHA? What test is used to detect the possibility of this occurring?
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Erythroblastosis fetalis. INDIRECT Coombs' test will be POSITIVE.
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What will you see on a blood smear of a patient with microangiopathic anemia? Where is this pathology seen?
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Shistocytes (Helmet cells) -- d/t mechanical destruction of RBCs; Seen in DIC, TTP-HUS, SLE, malignant HTN.
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What causes macroangiopathic anemia?
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Prosthetic heart valves and aortic stenosis --> mechanical destruction of RBCs + schistocytes on peripheral blood smear.
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What bugs chomp up RBCs?
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Plasmodium spp. (malaria) and Babesia.
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What drug can improve the sx of sickle cell disease? What is the mechanism of this drug?
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Hydroxyurea; Inhibits ribonucleotide reductase but also STIMULATES HbF PRODUCTION!!.
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Cold agglutinins are nearly always seen in which infections?
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Mycoplasma pneumoniae and EBV.
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Who carries around vWF in the blood? Where else is vWF found?
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Factor VIII; endothelial cells of blood vessels.
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What causes ITP?
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Auto-antibodies to GpIIb/IIIa --> decreased platelet survival.
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What is the defect in Bernard-Soulier disease?
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Deficient GpIb --> poor platelet to collagen adhesion.
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What is the lifespan of a platelet?
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8-10 days.
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What molecule is expressed on the surface of a platelet after it becomes activated? To what does this molecule bind?
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GpIIb/IIIa; binds fibrinogen, which links it to another platelet GpIIb/IIIa.
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What is the mechanism of action for Clopidogrel and Ticlopidine? SE?
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Inhibits platelet aggregation by blocking the platelet's ADP receptor --> prevents expression of GpIIb/IIIa --> no binding to fibrinogen --> no linking to other platelets --> no aggregation; NASTY BONE MARROW SUPPRESSION.
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What is the clinical use for Clopidogrel and Ticlopidine?
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Acute coronary syndrome, coronary stenting.
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What is the mechanism of action for Abciximab? What's the indication?
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Monoclonal antibody to GpIIb/IIIa --> binds GpIIb/IIIa on activated platelets --> prevents platelet aggregation; acute coronary syndromes, particularly NON-STEMIs.
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What structure is pathognomonic for a MYELOID leukemia?
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Auer Rods.
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What are faggot cells? What are they pathognomonic for? What is the chromosomal abnormality in this disease?
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Blasts with stacks of Auer rods; Pathognomonic for AML--M3; t(15;17).
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What is used to treat AML-M3? What is the risk associated with tx of AML-M3?
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all-trans retinoic acid (vitamin A) --> matures myeloblasts. If this isn't done, lysis of the myeloblasts will release auer rods, which can elicit DIC.
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Which type of disorder has cells that are CD13 and CD33 + and is PAS - ? Who is at increased risk for developing this dx?
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AML; patients with myeloproliferative disease, myelodysplastic syndrome, aplastic anemia, Down syndrome, Fanconi syndrom, or Bloom syndrome.
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What is the name for peroxidase-positive cytoplasmic inclusions in granulocytes and myeloblasts? Which disease do you see these in? What is the average age of onset?
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Auer rods. AML (2-3). 50 yrs old.
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Greater than 20% blasts in the bone marrow is the cut-off for diagnosing this disease.
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AML.
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What is the chromosomal abnormality in the most common leukemia of U.S. adults? Which genes is it always associated with? What do these genes encode for? What is the tx?
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Philadelphia chromosome: t(9;22); bcr-abl genes; bcr-abl encodes for a mutant tyrosine kinase receptor that is constitutively active; Tx is Imatinib.
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The disease shows hyperplasia of all three cell lines (granulocytic, erythroid, and megakaryocytic), but granulocyte precursors predominate.
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CML.
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What is the average age of onset for CML? What are the presenting sx? What cell will you see under the microscope that will make you shout "CML! CML!"?
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25-60 years old; Sx: fatigue, abdominal pain, splenomegaly, bleeding tendency; BASOPHILS.
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This is the most common leukemia in children, often presents with bone pain, and cells are PAS +.
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ALL.
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A 11 y/o male presents with bone pain and a mediastinal mass; cytology reveals TdT+ cells. What is the diagnosis? What chromosomal alteration gives him a better prognosis?
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ALL; t(12;21).
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What congenital syndrome is ALL associated with?
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Down Syndrome.
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Who gets SLL/CLL? What are the presenting sx? What will you see on a peripheral blood smear? What other pathological process goes on?
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People >60 yrs old; Often asymptomatic; SMUDGE CELLS under the microscope; Warm antibody (Which isotype?...IgG!) autoimmune hemolysis.
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What's the difference between SLL and CLL?
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They are the same, but CLL has increased peripheral blood lymphocytes.
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You see a cell under the microscope with filamentous, hairlike projections. It stains TRAP+. What is it? Who has it?
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Hairy cell leukemia; Adults and elderly.
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What are the chronic myeloproliferative disorders? Which mutation is common to all of them but one? Which one doesn't have this mutation?
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Polycythemia vera, Essential thrombocytosis, Myelofibrosis, CML; JAK2 mutation (hematopoietic growth factor signaling); CML.
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What type of Ig is overproduced in multiple myeloma? What will you see on x-ray? What will you see on protein electrophoresis? What will you see on a blood smear? UA?
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IgG (55%) and IgA (25%); punched-out lytic bone lesions on x-ray; M spike; Numerous plasma cells with "clockface chromatin" and intracytoplasmic inclusions containing Ig, also rouleaux formation; Bence Jones proteins (Ig LIGHT CHAINS) in urine.
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What are the presenting sx of multiple myeloma?
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"CRAB": hypercalcemia, renal insufficiency, anemia, bone lytic lesions/back pain.
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What are some toxic changes you will see in a leukemoid reaction?
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Granulocytosis, vacuoles, Dohle bodies.
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What cellular finding makes for a better prognosis in Hodgkin lymphoma?
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Increased lymphocyte to Reed-Sternberg cell ratio.
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What type of Hodgkin lymphoma will you find lacunar cell variants of the Reed-Sternberg cell?
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Nodular sclerosing.
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What type of cell does the R-S cell originate from? What are its cell surface markers?
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B cell; CD30+ and CD15+
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In what type of lymphoma will you see mediastinal involvement, constitutional sx, and an association with EBV infection?
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Hodgkin lymphoma.
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Which type of lymphoma is associated with multiple, peripheral node involvement, extranodal involvement and noncontiguous spread?
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Non-Hodgkin lymphoma.
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What is the most common adult non-Hodgkin lymphoma?
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Diffuse large B-cell lymphoma.
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What is the chromosomal abnormality in Burkitt's lymphoma? What gene is this associated with? What infection is Burkitt's lymphoma associated with?
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t(8;14); c-myc gene (moves next to heavy Ig chain gene, 14); EBV infection.
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Who gets Burkitt's lymphoma? What does it look like under the microscope?
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Adolescents or young adults; STARRY SKY appearnace -- sheets of lymphocytes with interspersed macrophages.
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What is the genetic defect in mantle cell lymphoma? What gene is associated with this?
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t(11;14); DEACTIVATION of Cyclin D regulatory gene --> cell progresses through cell cycle uninhibited.
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Who gets follicular lymphoma? What is the genetic defect in this disease? What gene is associated with this?
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Adults; t(14;18); bcl-2 expression --> inhibits apoptosis. Poor prognosis.
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Who gets adult T-cell lymphoma? What causes this?
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Adults in Japan, West Africa, and Caribbean populations; HTLV-1 infection. Present with cutaneous lesions.
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How does Mycosis fungoides/Sèzary syndrome present? What do the cells look like?
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Adults present with cutaneous patches/nodule; Under the microscope the patient's blood will show CEREBRIFORM cells! Little brains!
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