Heme/Onc Flashcards
How does Factor V Leiden cause hypercoagulable state?
Usually activated protein C proteolytically inactivates Va (and VIIIa). Va Leiden doesn’t get cleaved as well. Furthermore, Va helps prothrombin - >thrombin.
How prevent tumor lysis syndrome?
Hydration and hypouricemic agents like allopurinol (xanthinse oxidase inhibitor) or rasburicase (urate oxidase which makes uric acid into allantoin)
Hydroxyurea tx for sickle cell?
Increases Hb F synthesis by unknown mechanism. Use for those w/ freq. pain crisis.
HUS
Microangiopathic hemolytic anemia, thrombocytopenia, renal insufficiency. Typically after EHEC O157:H7 -> hemorrhagic diarrhea and cramping, undercooked beef/unpasteurized milk. Endothelial injury > isolated activation of PLT = micro thrombi -> schistocytes w/o coagulation system activation (DIC).
HbC?
Glutamic acid -> Lysine (Neg to POS). Less movt non electrophoresis.
FFP vs. Cryoprecipitate
FFP contains all coagulation factors. Cryo only contains cold-soluble proteins (VIII, fibrinogen, vWF, vitronectin, XIII). Cold F-Eight von Vitronectin!
High dose ADH affects coagulation how?
Increases factor VIII activity in pts with Hemophilia A and von Willebrand disease.
Von willebrand Disease
AD with variable penetrance. vWF is mediator of platelet adhesion. Absence leads to function factor VIII and pot deficiency = inc. PTT and inc. bleeding time.
Where does 2,3-DPG bind?
To the two beta subunits of HbA after Hgb is deoxygenated. HbF (2 alpha, 2 gamma) does NOT bind to 2,3-DPG as well, so binds to O2 with HIGHER affinity (usu. bad, except helpful for HbF).
Polycythemia vera
Plethoric face, splenomegaly, peptic ulceration, itching, gouty arthritis. Mutation in JAK2 = non-receptor tyrosine kinase associated with EPO receptor. Constiutive kinase activation -> inc. production of blood cells.
Vincristine, bleomycin, doxorubicin, cyclophosphamide side effects
Vincristine - neurotoxicity. Bleomycin - pulmonary fibrosis and flagellate skin discoloration, doxo - CHF, cyclo - hemorrhagic cystitis.
Precursor B-ALL vs T-ALL immunophenotypes
TdT+, CD10+, CD19+ vs. all T-cell (CD2,3,4,5,7,8), TdT, and CD1a
Mature B-cell leukemia immunophenotypes
CD19 and co-express CD5 (T-cell)
Hemophilia A vs. B
VIII vs. IX. Both have isolated PTT elongation.
Desmopressin acetate effect on clotting?
Releases vWF and VIII (think Hemophilia A) from the endothelium.
Plummer-Vinson/Patterson Kelly Syndrome
Formation of esophageal webs 2/2 to Fe-deficiency anemia -> dsyphagia. Disfigured fingernails are also specific for Fe-deficiency anemia. Atrophic glossitis
How do parasethesias occur after pRBC transfer?
Citrate in transfusions can chelate Ca+ –> hypocalcemia. Requires massive transfusions (5-6L/24h)
Reticulocyte characteristic
Immature RBC that is slightly LARGER and BLUER (2/2 ribosomal RNA). Lacks cell nucleus.
BCR-ABL
CML (chromosome 9 to chromosome 22). Imatinib.
t(8;14)
Burkitt lymphoma
Acute promyelocytic leukemia
Subset of AML. Can present with persistent infection and COAGULOPATHY -> hemorrhagic signs and symptoms. Biopsy with promyelocytes with intracytoplasmia AUER rods. t(15;17) -> alpha RETINOIC acid receptor w/ PML.
Histopath of follicular lymphoma?
LN biopsy shows aggregates of packed follicles. Mostly centrocytes > centroblasts (larger). T(14;18) w/ BCL-2 over-expression.
ITP vs. DIC?
ITP has ISOLATED thrombocytopenia (dec. plt count and increased bleeding time). DIC has throbocytopenia, INC PT, PTT, DEC plasma fibrinogen, and RBC fragmentation.
TTP vs. HUS?
Disease spectrum w/ pentad of fever, neuro, ARF, thrombocytopenia, microangiopathic hemolytic anemia. TTP adults w/ neuro. HUS children with renal. NO COAG involvement.
Osmotic fragility test
Spherocytes are more susceptible to hypertonic saline. Sickle cells are NOT.
Complications of hereditary spherocytosis?
Pigment gallstones, asplastic crises 2/2 parvovirus B19
What are the important platelet receptors?
GpIb for vWF receptor. GpIIb/IIIa for fibrinogen receptor.
What granules do platelets carry?
Dense granules (ADP and Ca2). Alpha granules (vWF, fibrinogen)
Hypersegmented polys?
Vitamin B12/folate deficiency
Surface marker for macrophages?
CD13, CD14, CD15, CD64
Causes of eosinophilia?
NAACP = Neoplasia, Asthma, Allergic processes, Connective tissue diseases, Parasites
Basophil function?
Mediates allergic reaction. Basophilic granules contain heparin, histamine, leukotrienes (SRS-A: “slow reacting substance of anaphylaxis”)
What drug prevents mast cell degranulation?
Cromolyn sodium
B lymphocyte CD’s?
CD 19, CD20.
Treatment to prevent hemolytic disease of the newborn?
Rho(D) immune globulin. Which is IgG (there CAN cross placenta but doesn’t cause disease b/c it is in low levels….) Apparently IgG > IgM, so that’s why they use IgG.
Roles of bradykinin
Vasodilation, increased permeability, and increased pain. Produced by cleavage of HMWK by kallikrein
Fibrin vs. Plasmin?
Fibrin is used for making clots. Plasmin is used to break said clots.
What coagulation factors does IIa activate?
Factors VIII, V, and XIII.
Extrinsic pathway key?
TF:VIIa
At what point do the intrinsic and extrinsic pathways coalesce?
In activating factor X. Because factor X (w/ Ca, PL, and Va) activates II.
Factor V Leiden mutation?
Produces a factor V that is RESISTANT to CLEAVAGE by Protein C.
Protein C pathway?
Activated via thrombin-thrombomodulin complex, then with Protein S, cleaves and inactivates Va and VIIIa. “Chad Ocho Cinco.”
What factors does anti-thrombin inhibits?
1972 + XI and XII.
Walk me through platelet plug formation.
Exposed collagen. vWF binds to it. Attracts PLT via GpIb receptor inducing release of ADP and Ca2+. ADP induces GpIIb/IIIa receptor expression, which attracts fibrinogen to LINK platelets. Now it’s a fight between TXA2 and PGI2/NO.
Ristocetin
Activates Gp1B-vWF interaction.
Drugs inhibiting ADP induction of GpIIb/IIIa receptor expression
Clopidogrel, ticlopidine, prasugrel, ticagrelor
Glanzmann thrombasthenia
Deficiency in GpIIb/IIIa
Bernard-Soulier syndrome
Deficiency in Gp1B
Causes of decreased ESR?
Polycythemia, sickle cell anemia, CHF, microcytosis, hypofibrinogenemia.
Acanthocyte
Spiny, “spur cell.” Liver disease, abetalipoproteinemia
Basophilic stippling
Anemia of chronic disease, alcohol abuse, lead poisoning, thalassemias
Schistocyte
“Helmet” cell. DIC, TTP/HUS, traumatic hemolysis (e.g. mechanical heart valve)
Teardrop cell
Bone marrow infiltration
Target cell
HbC disease, Asplenia, Liver disease, Thalassemia
Heinz bodies
Seen in G6PD w/ crystal violet stin.
Howell-Jolley bodies
Basophilic nuclear remnants usu. removed by functioning splenic macrophages. May be sign of hyposplenia/asplenia
Etiological differences between alpha and beta-thalassemias?
Alpha thalassemias are due to the deletion of the four alpha globin genes. Beta thalamssemias are often due to mutations of splicing/promoting problems that decrease the amount of Beta-globin synthesis. Alpha not seen on electrophoresis but Beta does.
Lead poisoning physical findings and lab findings?
Burton lines (Gingivae) and lead lines on long-bones. Wrist/foot drop. Sideroblastic microcytic anemia. Accumulated protoporhyrin and d-ALA
Lead poisoning mech and treatment?
Mech - inhibits ferrochelatase and ALA dehydratase -> decreased heme synthesis and increased RBC protoporphyrin. Tx = EDTA and dimercaprol.
Causes of sideroblastic anemia?
EtOH (mitochondrial damage), vitamin B6 deficiency/INH (ALA synthase problem), X-linked defect in ALA synthase gene, lead poisoning. Tx = pyridoxine