Drug Induced Blood disorder

  1. symptoms if plt count 30-50,000/mm3
    excessive bruise with minor trauma
  2. symptoms if plt count 10-30,000/mm3
    • petechiae
    • ecchymoses spontaneous
  3. symptoms if plt count <10,000/mm3
    risk of internal bleeding spontaneously
  4. thrombocytopenia can occur b/c of impaired production of plt. what kind of disorders can cause this?
    • disorders that damage stem cell or impair stem cell proliferation.
    • i.e. marrow aplasia, fibrosis, malignant infiltration, cytotoxic chemotherapy
  5. drugs that can cause thrombocytopenia. do they persist after d/c? (s40)
    • thiazide diuretic, ethanol, estrogen, linezolid (>2wk)
    • persist for months after drug d/c
  6. ___ sequestration can cause thrombocytopenia. it includes these two conditions. (s41)
    • splenic
    • portal hypertension, malignant splenic infiltration
  7. heparin induced platelet clumping can yield undercount of plt. effect is mild and early in tx. this is immune or non-immune effect?
    non-immune direct effect on platelet
  8. pathophys of immune thrombocytopenia
    • immune response with Ab targeting platelet for destruction by either -->
    • hapten type rxn
    • innocent bystander
  9. onset of immune thrombocytopenia
    • 6-12d of heparin (variable with other agents)
    • if prior heparin exposure, onset is in 1-4d (esp if in the last 100 days)
  10. how to you manage immune thrombocytopenia
    • drug withdrawal leads to plt count recovery (7-10d generally)
    • but if drug deposits in the body, it takes longer
  11. which one is exposure dependent, not concentration dependent, for thrombocytopenia?
    (the other three are conc dep)

    A) heparin
  12. petechiae is pinpoint hemorrhage that is ___mm in diameter. purpura is __mm in diameter.
    • <2mm
    • 2-10mm
  13. Reversible?
    a) type I (HAT)
    b) type II (HIT)
    a) type I (HAT)
  14. transient within few days of starting heparin
    a) type I (HAT)
    b) type II (HIT)
    a) type I (HAT)
  15. onset is 1-4 days
    a) type I (HAT)
    b) type II (HIT)
    a) type I (HAT)
  16. may not require stopping heparin
    a) type I (HAT)
    b) type II (HIT)
  17. platelet level is ~100,000/mm3
    a) type I (HAT)
    b) type II (HIT)
  18. delayed and serious
    a) type I (HAT)
    b) type II (HIT)
  19. platelet <100,000 or >50% decrease.
    a) type I (HAT)
    b) type II (HIT)
  20. requires d/c of heparin
    a) type I (HAT)
    b) type II (HIT)
  21. onset 5-12 d, sooner if prior use of heparin
    a) type I (HAT)
    b) type II (HIT)
  22. immune mediated: IgG and IgM antibody against heparin-platelet factor I complex.
    a) type I (HAT)
    b) type II (HIT)
  23. check antibody b/c this is an autoimmune process.
    a) type I (HAT)
    b) type II (HIT)
  24. may react with endothelial bound plt factor 4 leading to plt aggregation. clotting.
    a) type I (HAT)
    b) type II (HIT)
  25. hep-induced thrombo:
    does LMWH cross react with heparin? what else can you use?
    • yes
    • danaparoid (inhibit activated factor x)
  26. hep-induced thrombo:
    can you switch to lovenox if hep-ind thromb?
    • nope
    • cross reactivity
  27. if severe, can heparin be used in central line and peripheral line flushes?
  28. when do you support with platelet if hep-ind thrombocytopenia?
    when bleeding or platelet <10,000.
  29. what to do in continued anticoagulation in HIT?
    tx of choice?
    • d/c heparin and LMWH
    • could start warfarin (only when plt is normal)
    • tx: lepirudin, argatroban, fondaparinux
    brand name.
    pharmacological class.
    target and monitor.
    important to remember.
    • Refludan
    • direct thrombin inhibitor
    • aPTT 1.5-2 nl (can adjust q4h)
    • monitor platelet, PTT, renal fx, bleeding, allergy, fever, liver fx.
    • RENALLY adjusted
    pharmacological class
    when to adjust dose?
    how to monitor aPTT? when does it normalize?
    what else to monitor?
    • reversible thrombin inhibitor
    • caution in LP, severe htn, major surgery
    • adjust dose when hepatic issue
    • monitor q2h, adjust to 1.5-3 x nl. normalize w/i 2h of d/c drug
    • monitor platelet, apTT
    • SE bleed, hotn, allergy, GI
    brand name.
    pharm class.
    when to dose adjust.
    • Arixtra
    • synthetic pentasaccharide
    • bind to antithrombin III, potentiate factor Xa neutralization and inhibit thrombin formation. (3 and 10)
    • dose adjust when renal
    • CI when CrCl<30 and antiplatelet Ab present.
    • monitor platelet and anti-factor Xa
    • SE bleed, fever, rash
    pharm class
    pharm action
    does it cross react?
    • LMWH
    • inhibit thrombin via anti Xa and anti IIA (2 and 10)
    • indicated for subacute and acute event tx of venous or arterial thromboembolism.
    • SE bleed, fever, NV, constipation, rash
    • cross react 10-30%
  34. check aPTT in 2 h -->
    check aPTT in 4 h -->
    a) argatroban
    b) lepirudin
    • 2h for arga
    • 4h for lepi
  35. renal dysfx use -->
    hepatic dysfx use -->
    a) argatroban
    b) lepirudin
    • renal: use argatroban
    • hepatic: lepirudin (Liver for Lepi)
  36. what to monitor in both argatroban and lepirudin?
    • goal apTT (1.5-3 x baseline for arga and 1.5 - 2.5 x baseline for lepi)
    • platelet
  37. define leukopenia.
    WBC <3000 cells/mm3
  38. define granulocytopenia
    • granulocyte <1500 cells/mm3
    • (includes neutrophil, basophil, eosinophil, bands)
  39. define agranulocytosis.
    granylocyte <2000 cells/mm3
  40. define neutropenia.
    • ANC < 500 cells/mm3
    • or ANC of 1000 cells/mm3 with expected decline of <500 cells/mm3
  41. risks for neutropenia
    • renal fail
    • autoimmune disease
    • genetic
  42. another name for "segs"?
  43. calculate ANC.
    WBC 1.4
    segs 16%
    bands 20%
    lymph 60%
    eos 2%
    baso 2%
    • ANC = WBC x (% of seg + band)
    • 1400 x (0.16 + 0.20) = 504
    • this is not severe. severe is <500.
  44. onset of neutropenia and resolution time.
    what to do if not resolve?
    • 7-14 d onset
    • 10-14 d resolve
    • bone marrow aspirate and biopsy
  45. most common cause of neutropenia is...
  46. drugs for drug induced neutropenia?
    • clozapine (need to register w/ company. check q2w)
    • carbamazepine
    • chemotx
    • (also chloramphenicol, sulfa, sulfonylurea, phenylbutazone, felbamate, colchcine, dapsone, ganciclovir, methimazole, gold salts, isoniazid)
  47. S&S of neutropenia
    • FEVER!!!
    • usually blunted, malaise, chill, sore throat, pharyngitis, mouth ulcer, oral thrush, vaginal yeast infxn, diarrhea, infxn (bacteremia, sepsis, pna, cellulitis, uti)
  48. if ANC is < ___, whether you have fever or not you MUST treat.
    • 500
    • if 500-1500, just monitor. treat if fever present
  49. 2 mechanisms of neutropenia
    • immune mediated
    • direct toxic effect on bone marrow
  50. 5 agents that cause immune mediated neutropenia.
    • this is Ig induced peripheral destruction of cells.
    • carbamazepine, clozapine, chlorpropamide, methimazole, PTU
    • (CCCMP)
  51. 5 agents that cause neutropenia by direct toxic effect on the bone marrow.
    chemo, cimetidine, quinidine, ticlopidine, sulfonamide
  52. 2 agents that cause neutropenia via both mechanisms (immune-med and direct tox)
    • clozapine
    • flecainide
  53. how to manage neutropenia
    • d/c suspected agent
    • avoid sick ppl, fresh fruit/flower; barrier
    • face mask not necessary
    • wash hands
  54. neutropenic fever (NF) is medical emergency!
    how to manage?
    • broad spectrum pseudo
    • vanco only if G+ infxn
    • add fungal if no improve after 5-7d
  55. if you expect long course or high risk of neutropenia management, what to use? when are these indicated (ANC level).
    • Colony stimulating factor:
    • Filgrastim (Neupogen) 5mcg/kg/d sq
    • Peg-filgrastim (Neulasta) 6mg q14-21d sq
    • Sargramostim (Leukin) 250mcg/kg/d sq
  56. what to monitor for neutropenia?
    • temp
    • CBC w/ differential
    • S&S of infxn
    • SE of treatment
  57. aplastic anemia. what does BM bx show?
    decreased cellularity
  58. what is aplastic anemia?
    combo of 2 or more of neutropenia, thrombocytopenia or anemia
  59. S&S of aplastic anemia
    • fever, fatigue
    • malaise, chill, thrush, vaginal yeast infxn, mouth ulcer, diarrhea, infxn (b/c neutropenia), SOB (b/c lack of Hgb), dyspnea on exertion, weak, pallor, petechia, bruise (b/c low platelet), bleed
  60. drugs that induce aplastic anemia.
    • NSAID (indomethacin, diclofenac, aspirin)
    • beta lactam abx
    • phenytoin, felbamate, phenobarb
    • chlorpromazine, lithium
    • interferon
    • chlormaphenicol, chloroquine, sulfonamide (furosemide), captopril, enalaprin, methyldopa, quinidine
  61. what med to give when MS? how often monitor? impt blood disorder SE?
    • interferon
    • monitor q month for CBC, WBC
    • aplastic anemia
  62. how to manage aplastic anemia?
    • treat NF
    • immunosuppression
  63. current therapy of choice for aplastic anemia
    • stem cell transplant
    • ATGAM 40mg/kg/d IV x 4d
    • CSA 12mg/kg/d for adults div bid
    • methylprednisolone 1mg/kg IV qd
    • (+/- colony stimulating growth factor filgrastim 5mcg/kg sq qd)
  64. dosage of ATGAM for immunosuppression in aplastic anemia.
    • test dose required: 0.1ml intradermal of 1:1000 dilution
    • option 1: 10-20mg/kg/d IV qd x8-14d (long course)
    • option 2: 40mg/kg/d IV x 4d (preferred; short)
  65. how to decrease serum sickness when using ATGAM for aplastic anemia? what is serum sickness
    • use methylprednisolone 1mg/kg IV qd (minimum of 40mg) (3-5d)
    • fever, hypotension
  66. prednisone:methylprednisolone = __mg:__mg
  67. ATGAM (for aplastic anemia) stands for
    antithymocyte globulin
  68. ATGAM toxicity (this is for aplastic anemia)
    • anemia, thrombocytopenia, neutropenia
    • hypersensitivity rxn (thus need test dose; anaphylaxis, serum sickness, HA, chill, arthralgia, fever, rash, edema, joint pain, hotn, infxn, resp distress)
  69. MoA of cyclosporine A (this is for aplastic anemia)
    inhibit lymphocyte fxn from bone marrow
  70. dose for cyclosporine for immunosuppression in aplastic anemia.
    • 12mg/kg/d for adults
    • 15mg/kg/d for children (higher)
  71. what to monitor for cyclosporine (aplastic anemia)
    whole blood level 200-400 ng/ml
  72. toxicity of cyclosporine (this is for aplastic anemia)
    • renal tox
    • htn
    • cns
    • Mg loss (thus ALL needs Mg supple)
  73. which agents increase CSA level?
    • 3A4 inhibitors:
    • fluconazole, macrolides, metoclopramide, amiodarone, danazle, testosterone, CCB, oral contraceptive
  74. which agents decrease CSA level?
    • 3A4 inducers:
    • carbamazepine, phenobarbital, phenytoin
    • rifampin, rifabutin
    • bactrim
    • ketoconazole
    • imipenem
  75. what to evaluate in anemia?
    • Hgb/Hct
    • MCV, MCH, MCHC
    • as indicated: iron, B12, folate panel
    • as indicated: Coomb's test
  76. what's Coomb test? what is direct vs. indirect
    • to see if antibody is attacking RBC
    • indirect: see if antibody to RBC; done before blood transfusion
    • direct: see if antibody on RBC surface; to check if hemolytic anemia.
  77. what happen to Hgb and Hct if a lot of reticulocyte (immature RBC)?
    hgb and hct low
  78. when do you adjust for reticulocyte? what's the formula of corrected reticulocyte?
    • should be adjusted if low hematocrit and reticulocyte is >1%
    • corrected reticulocyte(%) = (observed reticulocyte count) x (patient's hct/ normal hct)
  79. etiology of anemia
    • decreased production: bone marrow injury, nutrition deficiency, endocrine dysfunct (hypothyroidism)
    • increased destruction, loss: hemorrhage, hemolytic anemia
    • hereditary: thalassemia, sickle cell anemia
    • deficient synthesis: hepatic insufficiency, chronic disease (CKD)
    • damage to RBC: spleen sequestration
  80. mechanism of immune hemolytic anemia
    • destruction of RBC by antibody to antigen on erythrocyte membrane: drug depdent and independent antibody, non-immunologic protein adsorption
    • mediated by either IgG or IgM (antibodies)
  81. immune hemolytic anemia signs and symptoms
    • pale, fatigue, SOB, dark urine, inc HR
    • inc: bili (yellow), haptoglobin, reticulocyte count, K+
    • dec: hgb, hct
    • hemolysis
    • (+) coomb test (esp direct)
  82. drugs that cause hemolytic anemia
    • cephalosporin
    • methyldopa (alpha agonist)
    • NSAIDs
    • sulfonamides (bactrim, sulfasalazine)
    • quinidine
  83. immune hemolytic anemia:
    mechanism of this anemia? when do symptoms occur?
    what to do??
    • generate drug-independent auto-ab --> stick to RBC then lysis.
    • 3-6 mo , usually mild
    • d/c meds!
  84. fludarabine can have auto-immune hemolytic anemia. how to decrease risk?
    combine with rituxumab and cyclophosphamide
  85. quinidine:
    what anemia?
    • hemolytic anemia
    • formation of immune complexes
    • bind to RBC membrane at allo-antigen site --> antigen-drug complex (neoantigen) activates complement --> rapid, acute, severe hemolysis
    • d/c drug, supportive care (transfusion, prednisone, immunosupp, IVIg, dialysis)
  86. drugs that cause hemolytic anemia via "drug adsorption" mechanism.
    pcn, cephalo, tetracycline
  87. what blood disorder do pcn, cephalo and tetracycline cause?
    • hemolytic anemia
    • drug adsorption: direct, covalent adsoprtion to RBC membrane --> splenic sequestration or direct lysis
    • stop drug or reduce dose (b/c usually mild and happens at high dose)
  88. methyldopa.
    what kind of anemia?
    • drug independent auto-ab
    • hemolytic anemia
    • could persist even after d/c drug
  89. cephalosporin:
    what kind of anemia
    hemolytic anemia (drug adsorption and non-immune drug adsorption)
  90. what drug causes hemolytic anemia via non-immune drug adsorption?
    how to manage
    • cephalosporin
    • bind to RBC membrane --> bind to other protein
    • no hemolysis
    • no treatment needed
  91. G6PD deficiency causes immune or non-immune hemolytic anemia?
  92. G6PD deficiency is common in which population?
    • African blacks
    • mediterranean (greek)
    • sephardic jews
    • chinese
    • these ppl don't have the enzyme so RBC destroyed
  93. in G6PD def, what condition can exacerbate hemolysis?
    oxidative environmental stress
  94. what to do for G6PD deficiency?
    • d/c drug
    • screen carefully - go for G6PD test
    • epoetin if hgb too low (<8)
    • hydration
  95. what drugs can induce G6PD hemolysis?
    • bactrim, sulfasoxazole
    • dapsone
    • pyridium (phenazopyridine)
    • nitrofurantoin
  96. once HIT is resolved, what would you start?
  97. if HIT type II, what should you check?
    • HIT antibody!
    • this is autoimmune dz
    • antibody to system and bind to platelet to destroy
  98. if warfarin is started before HIT/thrombocytopenia is resolved, what happens?
    venous gangrene
  99. what to monitor in hemolytic anemia?
    hgb, hct, haptoglobin, bili
  100. what should you NOT eat if you have G6PD def?
    fava beans (derr.?)
  101. normal platelet?
  102. normal hgb
    • men: 13.5 - 17.5 g/dL
    • women: 11.5 - 15.5 g/dL
  103. normal haptoglobin. what is it?
    • protein that binds to free hgb
    • 41-165 mg/dL
  104. what to consider in aplastic anemia (general management)
    • d/c drug!
    • broad spectrum abx (check PCN allergy and cx!! zosyn, aztreonam+gent, vanco)
    • neutropenic fever: tylenol
    • oral thrush and mouth sore: antifungal (nystatin, fluconazole, clotrimazole; no chlorexidine!)
    • ATGAM (test dose, methylprednisolone for serum sickness, tylenol, H1 or 2 blocker), or cyclosporine (check drug interaction)
    • transfuse blood if hgb <8
    • neupogen if ANC <500 (severe)
    • if young pt, allo SCT may help
  105. how to manage hemolytic anemia?
    • d/c agent
    • adequate hydration (NS 125-150ml/hr iv), may alkalinize urine (bicarbonate to IV fluid)
    • blood prodruct support if necessary (avoid if autoimmune hemolytic anemia) (only for severe, hgb <8 or sev sympt)
  106. when to avoid blood transfuse?
    when to give?
    • avoid if autoimmune dz (blood may hemolyze due to anti-RBC antibody b/c antibody still in the body)
    • give when severe sympt or hgb <8
Card Set
Drug Induced Blood disorder
Drug Induced Blood disorder