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165 Cards in this Set
- Front
- Back
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Treatment for AML?
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Induction - anthracycline/cytarabine
Consolidation - chemo/HSCT |
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Risks and AML?
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Good - 15/17
Bad - 5q, 7q, 9-22 |
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What is the good AML? How do you treat it?
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M3, 15-17 translocation. Treat with ATRA and follow up with AsO3.
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Side effects of ATRA?
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fever, fluid retention, pulm infiltrate, ARF. Called Retinoic Acid Syndrome.
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ALL Treatment
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Remember CNS prophylaxis.
Possible supportive care Induction - anthra Consolidation - Chemo/HSCT Maintenance - eliminate residual dz (Methoxtrate) |
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How does MDR work?
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binds ATP and chemo in cytoplasm, hydrolyzes ATP and pumps chemo out
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How does Methotrexate work? Class?
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Antifolate. Binds tightly to DHFR. Prevents creation of reduced folate and prevents reactions critical for purines and thymidines.
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What allows you to do high dose MTX?
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Leucovorin. Rescue!
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What are the purine analogues?
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6-mp; 6-TG
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What are the pyrimidine analogues?
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5-FU, Ara-c
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Mech of Ara-C. side effects?
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Inhibits DNA polymerase and ribonucleotide reductase. Severe myelosuppression.
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Mech of 5-FU?
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Inhibitor of thymidylate synthase
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Mechanism of anthracyclines?
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Intercalate with DNA and generate free radicals especially Fe.
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Side effects of anthracyclines?
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Myelosuppression, N/V, Cardiomyopathy. Give Zinecard/Dexrazoxane to chelate Fe.
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Mechanism of Vinca alkaloids?
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Bind tubulin. Dissociation of microtubules.
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Toxicity of vincristine?
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Peripheral neuropathy
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Example of anthracyclines?
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doxorubicin/adriamycin; daunorubicin/daunomycin
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Example of vinca alkaloids?
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Vincristine and vinlastine
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Mechanism of Taxol?
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Binds and stabilizes microtubules messing up spindles
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Mechanism of epipodophyllotoxins? side effects?
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Mess with topoisomerase. Second malignancy
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Example of epipodophyllotoxins
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Etoposide, teniposide
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Which are the protypical alkylating agents? Action? Side effects?
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Mustards. Cross-link DNA. Male sterility and secondary malignancy.
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What is the most widely used alkylating agent? Side effects?
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Cyclophosphamide.Hemorrhagic cystitis. Treat with MESNA to bind the agroline.
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What class are Platins? Side effects?
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Alkylating agents.Severe vomiting (worst), hearing loss
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Examples of platins
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Cisplatin carboplatin
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Newest antiemetic mechanism? Examples?
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5-HT3 sertonoin receptor antagonists. Better than the previous dopamine antagonists. Ondansetron is an example.
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What are the antimetabolites?
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Antifolates, purine analogues, pyrimidine analogues
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What are the natural substances?
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Anthracyclines, Vinca Alkaloids, Taxol, Epipodophyllotoxins
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What are the alkylating agents?
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Mustards, Platins, Cyclophosphamide
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Three sources for hematopoeitic progenitor cells?
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Bone marrow, peripheral after G-CSF, cord blood
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Benefits from peripheral hematopoietic stem cells?
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graft faster. Maybe higher risk for GVHD.
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Minimum acceptable match for HSCT?
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5/6
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Two types of HSCT chemos?
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Myeloablative = cytoreduction; Nonmyeloablative = immunosuppression and want GVL
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Acute GvHD targets?
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Skin (rash), GI tract and diarrhea, Liver
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Chronic GvHD targets?
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Veno-occlusive disease of the liver, DAD and hemorrhage of the lung
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How do you prevent or treat GvHD?
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Better HLA. Calcineurin inhibitors/MTX.
Rx: Cylosporine and Steroids |
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What is their a higher risk post HSCT?
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Second malignancies
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Bad risk factors for Diffuse large cell lymphomas
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old, performance status high, elevated LDH, high stage
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Treatment for Diffuse large cell lymphoma
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R-CHOP. Consider intrathecal CNS prophylaxis
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Prognosis for Follicular NHL
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pretty good but not curable unless HSCT. High age, high stage, low Hb, elevated LDH are bad.
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treatment for follicular NHL
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R-chop, possible HsCT for younger. also watchful waiting. Single alkylating agents, and purine analogues. Radioimmunotherapy for those with low BM invovlement.
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Lymphoblastic lymphoma treatment and presentation
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Watch out. T cell rapid. ALL regimen. CNS prophylaxis. Do tumor lysis prophylaxis with Allopurinol and hydration: avoid high K, high uricemia, high P, low Ca.
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Risk factors for Hodgkin's
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EBV and HIV, high SES, high education, early birth order, small family - suggest delayed exposure to infectious agent
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What is pathognomonic for Hodgkin's?
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alcohol-induced pain in lymph nodes
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Diff in presentation with NHLs and HL
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Diffuse - 55yo, painful, B symtpoms. Follicular - older, asymptomatic painless. Burkitts - abdominal. Hodgkin - young and old bimodal. Painless lymphadenopathy
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Prognosis and Treatment for Hodgkins
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poor for early - bulky and old
poor for late - old, male, anemia early and good - short chemo and rad early and bad - chemo and rad advanced - combo chemo for 6months every 2 weeks - ABVD = adriamycin, bleomycin, vinblastine, dacarbazine |
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Side effects of Hodgkins treatment
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2ndary solid tumors, cardiac dz (pericarditis) from RAD
Chemo - cardiomyopathy, peripheral neuropathy, sterility |
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Triad for infexs mono?
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fever, adenopathy, pharyngitis
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Findings for infxs mono
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atypical lymphocytes, leucopenia followed by leukocytosis
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Complications of infxs mono
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splenic rupture, tonsilar hypertrophy (airway obstruction), HAs and thrombocytopenia from autoantibodies
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Double Whammy of CLL?
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Bone infiltration leading to anemia, neutropenia, and/or thrombocytopenia. But also hypogammaglobulinemia. See splenomegaly too.
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Important prognostic factors for CLL?
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Bad = 17p-, 11q-, Zap-70
really important = doubling time if less than 12 months |
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Indications for therapy for CLL?
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Any change or bad thing.
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Therapy for CLL?
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Watchful waiting! Otherwise, alkylating agents, purine analogues, monoclonal AB for refractory.
Younger - allogeneic HSCT |
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Presentation of Macroglobulinemia of Waldenstrom
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Splenomegaly. Hyperviscosity syndrome. String of sausage appearnce of retinal veins. CHF and expanded plasma volume. Renal failure.
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Path feature of Multiple Myeloma
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Rouleaux formation. Plasma cells in blood. immunosuppression from high Ig levels, also marrow replacement - anemia, thrombocytopenia, and leukocpenia. Renal failure, and amyloidosis.
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Therapy for Multiple Myeloma
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Standard dose chemo for older. Autologous HSCT - good.
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What does vWF bind?
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GPIb - leads to shape change and granule release of ADP.
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Classifications of thrombocytopenias?
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Increased destruction, decreased producion, sequestration
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What is TTP? Signs?
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MAHA, thrombocytopenia, neurologic dysfunction, renal failure, fever.
Due to Ig antibodies against ADAMTS13. leading to platelet aggregation - thromboses. |
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Treatment for TTP?
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Plasmaphresis
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What is vWF?
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binds to GPIb on platelet surface. Acts as bridge. Also carries factor VIII.Cleaved by ADAMTS13 to not cause giant platelet aggregations.
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What is Von willebrand disease? Dx?
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Bleeding of platelet dysfunction and/or factor VIII deficiency. Diagnose with multimer gel electrophoresis.
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Types of VWD?
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1 = partial quantitative VWF deficiency
2 = qualitative VWF deficiency 2A = decreased VWF platelet binding without large multimers 2B = increased VWF affinity for platelet GPIb 2M = decreased VWF binding with large multimers 2N = decreased affinity for factor VIII (like hemophilia A) 3= virtually complete VWF deficiency |
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Treament for VWD?
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DDAVP for type 1. Increases factor VIII too.
Possible factor VIII/VWF concentrates. |
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PT measures abnormalities in?
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Fibrinogen, II, VII, V, X
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aPPT measures abnormalities in?
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XI, X, IX, VIII, V, X, II, Fibrinogen.
also XII, HMWK, prekallikrein |
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What test do you perform to check for antibodes in coagulation?
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50:50 mix
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For what is Vit K required? When do you see deficiencies?
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II, VII, IX, and X; warfarin, malnutrition, antibiox, biliary obstruction.
See prolongation of PT |
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How does liver disease affect clotting times?
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II, VII, IX, X, XI, fibrinogen. decreased synth.
Rx: FFP, Liver transplant |
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How can you treat DIC? What is it?
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Consumption of clotting factors triggered by some event.
rx: cryo and FFP for bleeding. Heparin if thrombosing. fibrinolysis and coagulation gone rampant. |
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Rx for hemophilia?
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IV factor replacement. Prophylaxis with e-amino caproic acid or DDAVP for mild VIII deficiency. Watch out for new inhib antibodies.
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Treat arterial thrombosis with? Venous thrombosis?
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A = antiplatelets
V = anti thrombotics/fibrin |
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What does antithrombin inhibit?
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IIa, Xa, IXa
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Activation of protein C?
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Thrombomodulin changes thrombin to cleave protein C zymogen
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Factor V leiden and protein C deficiency lead to?
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Venous thrombosis
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Risk factors for VTE?
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factor V Leiden, plasma protein deficiencies, elevated plasma homocysteine, anti-phospholipid antibodies
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What is neonatal purpura fulminans?
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homozygous deficiency of protein C or S. Fatal if not treated with FFP or liver transplant.
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How do you treat VTE?
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Heparin overlapped with warfarin. Fibrinolytics. Vena cava filter.
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What is HIT? Fix it?
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heparin binding to PF4 and antibodies to these forming. Complexes activating platelets. Induction of tissue factor on endothelial cells leading to thrombin formation. Thrombosis then thrombocytopenia.
Hirudin or argatroban. |
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Warfarin blocks?
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II, VII, IX, X, C and S
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Warfarin Indicated for? How does it travel?
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VTE, a fib prevention of atrial thrombosis;
bound to proteins |
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With what is warfarin action correlated?
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PT/INR mirrors VII decrease. True benefit follows II.
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Complications from warfarin?
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Bleeding - give K or FFP
Teratogenic Skin necrosis - follow up with heparin |
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Functions of EPO?
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expansion of committed erythroid progenitors, shortened maturation time of RBCs, increased release of immature RBCs from marrow
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What does TPO do?
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stimulate platelet production by increasing marrow megakaryocytes and megakaryocyte progenitors
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What does G-CSF do?
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increases level of circulating neutrophils. Mobilizes progenitor cells from the bone marrow to blood. Modulates neutrophil function.
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Indications for G-CSF?
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myeloablative therapy, BMT, severe congenital neutropenia, HSCT mobilization
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EPO indications?
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GIVE IRON! CRF, Zidovudine HIV pts, certain CA pts, preoperative for nonvascular noncardiac surgery in anemic patients.
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What causes Chronic Granulomatous Disease?
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Lack of NADPH oxidase. Cannot kill certain organisms like e coli.
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How do you calculate Red Cell index?
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% retic x observed HCT/normal HCT x 1/2
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Sources for Target Cells?
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Liver dz, thalassemia, Hb C, low iron
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Serum markers for Fe deficiency?
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low Fe, high TIBC, low transferrin saturation, low ferritin
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Clinical features of Fe deficiency? Rx?
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Pica. Ferrous sulfate.
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What are people with Fe deficiency at risk of?
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Pb poisoning due to transferrin low saturation.
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Serum markers for anemia of chronic disease?
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Low serum iron. High ferritin. Low transferrin saturation. High hepcidin.
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Serum markers for HH, types 1-3?
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High serum iron. High ferritin. High transferrin saturation. Low hepcidin.
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Major features of HH?
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liver damage, pancreas damage, cardiac damage, skin damage.
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Types of HH
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1 - HFE mutations, reduces hepcidin production
II - low hepcidin. unknown why. III - transferrin receptor knockout. Thinks there's Fe deficiency. Increased absorption. IV - ferroportin mutation. Low hepcidin. |
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Rx for HH?
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Phlebotomy
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Consequences of ineffective erythropoiesis for megaloblastic anemia?
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pancytopenia, poikilo-anisocytosis, increased TIBC, higher ferritin, increased LDH, increased bilirubin, decreased haptoglobin, extramedullary hematopoiesis with time
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Signs of folate or B12 deficiency?
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pallor, icterus, glossitis
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Where is folic acid absorbed?
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jejunum
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What does folic acid circulate as?
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methyl-THF
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What is folic acid needed for?
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DNA synthesis and for production of dTMP from dUMP
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Causes of folic acid deficiency?
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Inadequate diet, impaired absorption, increased requirements (HA, pregnancy)
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Causes for impaired absorption of B12?
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lack of IF, HCl/pepsin, Zollinger-Ellison, decreased bicarb, lack of trypsin, ileal resection, Crohn's, sprue, bacterial competition, fish tapeworm
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Schilling test mechanics?
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saturate B-12, monitor radioactive B-12 in urine, try again after IF, antibiotics, pancreatic enzymes, B12 bound to protein to test HCl
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Dx deficiency in Folic acid or B12?
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Serum levels. then Folate = high Homocysteine. B12 = high MMA and homocysteine.
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Changes for treating megaloblastic anemia?
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Serum iron decreases, K decreases pretty much immediately. Normalization after 2 months. MCV, thrombocytopenia resolve in 10-14 days.
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Causes of macrocytosis?
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Alcohol abuse, Megaloblastic, Reticulocytosis, Liver dz, MDS, hypothyroidism
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Breakdown of hemoglobin types?
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95% = A = a2b2
2-3% = A2 = a2d2 1-2% = F = a2g2 |
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Sign of B thal?
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higher A2 than normal. May see increases in serum Fe and ferritin.
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Problems from thalassemia?
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Long bone damage from explosive growth, splenomegaly, increased Fe absorption and overload
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Rx for thalassemia?
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Splenectomy, iron chelation, lifelong transfusions
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When does SCD cells sickle?
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with low O2.
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What are treatment methods for ITP?
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Splenectomy, glucocorticoids, rituximab (for B cells)
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When does extramedullary hematopoiesis arise?
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IMF, when ineffective erythropoiesis has happened for a long time (Megaloblastic anemia, thalassemias)
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Dx for SCD?
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Hgb electrophoresis
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Complications of SCD?
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splenic sequestration, imapired growth and devo, delayed puberty. See increased retics and increase bone marrow activity.
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Good factors for ameliorating SCD?
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high HbF, heterozygosity with HbC or b thal mutations (less conc of polymer in RBC).
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Treatment for SCD?
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Hydroxyurea and increasing HbF. Pneumococcal prophylaxis.
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What is a thalassemic hemoglobinopathy?
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Hb E. unstable and also loss of expression.
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Signs of Hb EE?
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microcytosis severe, mild splenomegaly. Target cells. Normal levels of A2 and F. Mild anemia.
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Most common enzyme deficiency of glycolysis?
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pyruvate kinase deficiency
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Pathophysiology of G6PD deficiency?
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Lacks G6PD which is essential for reducing sulfhydryl groups. If oxidized, like by ETC agents/benzene rings like antimalarials, no way to reverse it. Get Heinz bodies. Macs and spleen phagocytize them.
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Dx for G6PD deficiency?
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Spot test.
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How does destruction arise in hereditary spherocytosis?
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intrinsic defect in RBCs render them vulnerable to premature entrapment and destruction in the spleen.
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How is hereditary spherocytosis inherited?
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AD
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Clinical features of HS?
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Mircrospherocytes, splenomegaly, jaundice with increased indirect bilirubin
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Treatment for HS?
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can take out spleen,
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Dx of HS?
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Osmotic fragility test. Lyse at higher concs of salt. But it only shows microspherocytes.
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Where are mutations for HS?
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ankyrin, then band3
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What type of lysis is G6PD?
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Intravascular. Should see lower haptoglobin.
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what type of hemolytic anemia is HS?
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Extravascular. Non-immune.
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Etiology of AIHA?
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Idiopathic, Lymphoproliferative diseases (CLL, HL), Collagen Vascular Dzs, Infections (myco = cold), syphilis = PCH
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Lab features of AIHA
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bilirubin increase, decrease in haptoglobin, higher retics, LDH higher
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Signs of Warm AIHA?
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see splenomegaly. Microspherocytes. Positive DC for IgG. Positve Indirect coombs.
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Treatment for Warm AIHA?
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Glucocorticoids, splenectomy, rituximab
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Signs for Cold AIHA?
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positive C3d for DC, cold agglutinin
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Treatment for Cold Agglutinin?
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Rituximab. Treat underlying B cell neoplasm. Avoid the cold.
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Signs for Paroxysmal Cold Hemoglobinuria?
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Direct Coombs for C3d, Donath-Landsteiner test
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Types for Drug-Induced AIHA?
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Covalent attachment (PCN) - Positive for DC IgG and C3d.
Ternary complex formation (quinine)- DC Positive for C3d. Negative for IgG. Induction of true autoantibodies (Aldomet) - DC Positive IgG. IC positive. |
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Treating Hemolytic Dz of the Newborn
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RhoGam (anti-D antibody)
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Shared mechanism of genes responsible for MPDs?
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Increased proliferation and/or survival. Preservation of differentiation.
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What does expression of BCR-ABL induce?
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cell prolif, survival, motility and adhesion, genomic instability
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Definition of blast crisis for CML?
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>20% blasts in blood, >30% blasts in BM
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CML presentation?
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splenomegaly, basophilia, thrombocytosis
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What is risk of progression to blast crisis for CML?
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first two years - 5-15%; then 20-25% per year
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Rx for CML
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GLEEVAC!!!, if young consider allo HSCT
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Treating Gleevac resistant CML?
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Nilotinib; Dual Bcr-abl/Src kinase inhibitor - Dasatinib
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Presentation and risks for PV?
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splenomegaly, erythromelalgia, thrombosis, pruritus
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Rx for PV?
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phlebotomy, myelosuppression (HU for RBC production prevention)
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ET presentation and risks?
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THROMBOSIS, spontaneous abortion, erythromelalgia, splenomegaly
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Initial bone marrow feature for MPDs?
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HYPERCELLULAR
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Rx for ET?
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Hydroxyurea for myelosuppression, low dose aspirin, anagrelide when intolerant of HU
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Presentation for IMF?
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Tear drop RBC, Nucleated RBCs, immature myeloid cells, marked splenomegaly, portal hypertension. Susceptibility to infections and hemorrhaging.
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Rx for IMF?
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HSCT. Supportive. Splenectomy. Lenalidomide for pancytopenias.
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Characteristics for aplastic anemia?
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NO SPLENOMEGALY. decreased cellularity. Pancytopenia. Poikilo-anisocytosis. Macrocytosis. No immature hematopoietic cells.
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Rx for aplastic anemia
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anti-thymocyte globulin, cyclosporine. HSCT for youths.
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Cause of PNH?
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no PIG-A gene. No GPI to bind DAF and C8 inhibitor. Increased complement activation. Can progress to AML but more often aplastic anemia.
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Dx for PNH?
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sucrose, acid test. Looking for anti-CD59 mAB. don't bind.
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MDS presentation?
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anemic, neutropenic, thrombocytopenic. Bone marrow - hypercellular or normocellular. Macrocytic anemia. Nucleated red cells. Can look like B12 deficiency. Hyposegmented neutrophils.
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Bad vs good MDS
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Bad = -7q. Good = 5q-, Y-, 20q
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Rx for MDS?
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Supportive care for late age patients - transfusion, G-CSF, perhaps EPO, antibiotics.
hypomethylating agents possibly Lenalidomide for pancytopenia - esp 5q- HSCT allogeneic only cure |
