Thrombosis Hematology

  1. Unfractionated heparin
    complex glycosaminoglycan purified from animal tissues
  2. Unfractionated heparin MOA
    binds with antithrombin III (heparin cofactor) accelerates its activity by blocking thrombosis via inactivation of Factor Xa and Factor IIa. (prothrombin to thrombin and fibrinogen to fibrin)
  3. Unfractionated Heparin indications
    • Treatment of DVT's and PE's
    • Acute coronary syndrome: STEMI
    • angina
    • Strokes (ischemic)
    • Prophylaxis (DVT/PE prevention)
  4. UF dosing
    • Prophylaxis: 5000 units q12 or q8h
    • General Treatment: BASED ON WEIGHT. bolus dose.
  5. UF monitoring
    • aPTT. normal ~ 30 sec.
    • Therapeutic aPTT - 50-80 seconds.
    • Hgb and hematocrit
    • Platelet count (stopping clotting cascade, may develop thrombocytopenia)
    • Overt signs/symptoms of bleeding.
  6. UF kinetics
    • Absorption: 2-4 hours peak concentration
    • Metabolism: hepatic and reticulo-endothelial system
    • Dialyzable: no
    • Elimination 1/2 life: 1.5 hr.
  7. UF Adverse effects
    • Dermatologic (SQ injections) reactions. local irritation.
    • Hematologic: can get internal pockets of bleeding, hematomas, heparin induced thrombocytopenia
    • Musculoskeletal: (LMW heparins) osteoporosis if longterm tx or high dose.
    • Other: bruising/bleeding. interrupting coagulation cascade.
  8. Management of UF adverse effects
    • Time. gone in about 1.5 hr.
    • Protamine (life threatening bleed) antidote for heparin.
    • Fresh Frozen Plasma (FFP) works almost immediately.
    • Recombinant Factor VIIa (rFVIIA) $$ (Novo Seven) not first line or 2nd line.
  9. UF Clinical PEARLS
    • Big people require big doses. Weight based. Know normal dose, know red flags- not necessarily wrong.
    • Quick onset, quick elimination.
  10. LMWH MOA
    • fragment of UF. work similarly
    • higher affinity to factor X, rather than factor II.
    • more predictable dose response (don't monitor as often)
    • equally effective
    • given SQ, outpatient setting.
  11. LMWH Indications
    • prophylaxis (bedridden, acute, surg)
    • treatment of DVT/PE
    • acute coronary syndromes
    • *not given for ischemic stroke*
    • *can't use with HIT*
  12. LMWH Kinetics
    • Absorption: time to peak 2-4h
    • Metabolism: renal excretion
    • Dialyzable: no
    • Elimination 1/2 life: 5-7 hrs (longer)
  13. LMWH Dosing
    • Prophylactic: set dose (Lovenox)
    • 30 q12 or 40 once daily.
    • Treatment: Lovenox WEIGHT BASED. Max dose limits. adjust dose with renal insufficiency.
    • Really obese- UF may be better to use.
  14. LMWH Adverse Effects
    • Dermatologic: injection site rxn
    • Hematologic: hematomas, bleeding internally, HIT
    • Musculoskeletal: osteoporosis. long-term dosing. more likely. check bone densities.
    • Other: increased bleeding/bruising
  15. LMWH Monitoring
    • Renal function (serum creatinine)
    • Platelet count
    • Hgb/Hematocrit (don't care if they are low, care if they change!)
    • Signs/symptoms of bleeding
    • Anti-Factor Xa (MOA- inhibit X to Xa conversion) cancer patients.
    • Pregnancy- keep close eye on anti-Xa level.
    • Protamine- can help some, but not much 40-50%.
  16. Anti Factor Xa levels
    • Peak at 4 hours after last injection
    • Trough just prior to next injection
    • why do I want to know?
    • do I have enough on board?
    • Therapeutic level 0.1-1.0
  17. Available LMWH
    • Lovenox (Enoxaparin)- only one with specific renal dosing guidelines. only one with generic available.
    • Fragmin (Dalteparin) (1x/day)
    • Innohep (Tinzaparin)
  18. Fondaparinux
    • synthetic LMWH
    • inhibits only FX
  19. Fondaparinux Indications
    • Same as LMWH
    • prophylaxis (bedridden, acute, surg)
    • treatment of DVT/PE
    • acute coronary syndromes
    • *not given for ischemic stroke*
    • *can't use with HIT*
  20. Fondaparinux dosing
    • Weight based dose
    • big dosing ranges. not per/kg dose
  21. Fondaparinux elimination
    • Renal excretion
    • protamine has no effect
  22. LMWH Clinical PEARLS
    • renally eliminated use caution! check levels
    • weight limits do apply. UF may be best bet.
  23. Warfarin (Coumadin) MOA
    • Vitamin K antagonist (stops carboxylation of 2, 7, 9, and 10)
    • inhibits Protein C and protein S (natural anticoagulants along w/ antithrombin)
    • most effects extrinsic pathway. factor 9 in intrinsic pathway.
    • 2 and 10 in common pathway.
  24. Warfarin Indications
    • DVT/PE
    • Atrial fibrillation- stroke prevention
    • Mechanical heart valve- stroke prevention
    • Severe left heart failure- left ventricular thrombus, stroke prevention
    • Myocardial RE-infarction- not primary MI
  25. Warfarin (relative) Contra-indications
    • active cancer (LMWH recommended does better)
    • patients whom Vit K intake not stable (NPO or otherwise)
    • unable or unwilling to return to clinic for monitoring. home monitors available but expensive.
  26. Warfarin dosing
    • Acute PE or DVT: achieve therapeutic anticoagulation with UFH or LMWH prior to initiating warfarin (takes a few days for warfarin to kick in).
    • Begin warfarin at 5mg daily, NO BOLUS
    • Adjust per INR
    • "Bridge" or treat active thrombosis with UFH or LMWH + warfarin x at least 5 days or until INR therapeutic (whichever longer) x 24 hrs once INR is therapeutic. (except A-fib or valve pts- no active clot, can just start warfarin and monitor INR)
  27. Initiating Warfarin
    • Check INR 2x weekly until therapeutic!!!
    • once therapeutic- check again make sure they are stable then decrease monitoring.
    • maximum 4-6 weeks monitoring of INR.
  28. Warfarin Genetic Testing
    • recommended
    • look at metabolism polymorphisms.
    • takes 3-5 days
    • results: tell if need more/less/average doses of warfarin. not very useful.
  29. Warfarin Drug Interactions
    • Any drug or herbal preparation has potential to interact with warfarin.
    • Antibiotics and antifungals: Septra, Cipro, metronidazole, fluconazole, Rifampin.
    • Amiodarone: decrease warfarin dose by 1/3 to 1/2
    • Anticonvulsants: phenytoin*, gabapentin, Depakote.
    • NSAIDS: ibuprofen, naproxen. have platelet effect- increased risk for bleeding (recommend Tylenol).
    • Celebrex (cox2) has lower platelet effect than typical NSAIDs.
    • either have to up dose and keep close eye on monitoring, or switch to LMWH.
    • CP450 enzyme
  30. Warfarin monitoring
    • check INR (normalized ratio based on PT)... PT/INR.
    • frequent monitoring until on stable dose, then q4-6 weeks.
    • signs/symptoms of bleeding "black tarry stools" "apple cider colored urine"
    • sx of new clot- swelling, erythema, acute stroke signs.
    • Changes in: Diet (foods rich in VitK), Dose, Disease (acute illness, vomiting/diarrhea), Drinks (etOH up or down), Drugs (new meds or herbal meds). Gingko, Ginseng, Green tea- interact.
  31. Warfarin Adverse effects
    • Supratherapeutic:
    • increased bleeding risk
    • Treat with Vit K if bleeding, FFP if severe bleed.
    • Subtherapeutic:
    • risk of recurrent DVT/PE or CVA
    • "bridge" back to therapeutic if extremely subtherapeutic with a recent event.
  32. Warfarin Patient Education
    • Verbal/written info provided
    • Dietary restrictions concerning Vit K (dark green leafy veggies moderation)
    • Signs/symptoms of hemorrhagic/thromboembolic complications
    • Drug interactions (alcohol, prescription drugs, OTCs)
    • recommended Med-Alert bracelet/necklace
    • Monitoring contract?
  33. Warfarin Clinical PEARLS
    • warfarin causes BIRTH DEFECTS (teratogenic)
    • patients should use adequate contraception- condoms not considered sufficient.
    • patients should be transitioned to LMWH prior to attempting pregnancy.
  34. Prophylaxis Options to Prevent a Clot
    • SCD's- mechanical (leg squeezers).
    • Low Molecular Weight Heparin
    • Fondaparinux
    • Unfractionated Heparin
    • Retrievable IVC filter (only for patients you can't do meds in) trauma patient, MVC patient, acute stroke. doesn't prevent DVT because of where they sit. prevent clot from traveling to lungs or head.
  35. Management of Acute DVT
    • acute extremity DVT - LMWH and managed without hospitalization.
    • unstable pt or patients unable to afford or administer LMWH- hospitalization for IV heparin or SC LMWH.
    • Draw baseline PT, ABC, SCr.
    • Initiate LMHW or IV UF
    • Continue UF/LMWH while transitioning to warfarin. overlap at least 5 days, 24h after therapeutic INR.
    • monitor CBC, PTT (if using heparin) and INR.
  36. How long to treat acute DVT?
    • transient risk factor (BC pills, pregnancy, PICC line)- 3 months
    • Isolated calf vein thrombosis- 3 months
    • unprovoked thrombosis- 3-12 months (consider indefinite)
    • significant underlying thrombophilia- 12 months (consider indefinite)
    • Recurrent VTE- indefinite
    • Cancer-related VTE- indefinite or until cancer is resolved. LMWH recommended first 3-6 months.
  37. Bridge Therapy
    • Initiation of warfarin in patients with new thrombosis
    • Patients on chronic oral anti-coagulation need normal coagulation for surgery/procedures.
    • as INR falls, LMWH is begun, keeping number of days with subtherapeutic anticoagulation to minimum.
  38. Bridging with LMWH
    • Last dose of warfarin 5 days prior to surgery.
    • therapeutic LMWH 24 hours prior to surg.
    • Post op LMWH and warfarin restarted when hemodynamically stable.
    • LMWH stopped when protime/INR is therapeutic.
  39. Heparin Induced Thrombocytopenia (HIT)
    • Timing: platelet drop of 50%
    • Thrombocytopenia: platelet count 30-50K after 5-10 days of heparin
    • Thrombosis: high risk of arterial and venous thrombosis.
    • Other: other causes of thrombocytopenia (sepsis, chemo, etc)
  40. HIT Lab Diagnosis
    • IF HIGH CLINICAL SUSPICION- send both functional assay (high spec, low sens) platelet aggregation, C-serotonin release, heparin induced platelet activation, flow cytometry
    • Serological assay (ELISA, gel particle) (low spec, high sens)
  41. HIT/HITT Treatment
    • STOP HEPARIN- including IV flushes
    • Reverse- Coumadin/warfarin if already initiated
    • Begin a direct thrombin (FII) inhibitor (DTI):
    • *Lepirudin (IV or SC, mg/kg/hr)
    • *Argatroban (IV only, mcg/kg/min)
    • *Bivalirudin (IV only, best for MODS)
    • *Fondaparinux (used when platelets normal, SQ injection outpatient)
  42. Direct Thrombin Inhibitors
    • Monitor similar to UFH:
    • *aPTT
    • *hbg/hematocrit/bleeding
    • *Platelet count
    • **May falsely elevate INR (chromogenic factor Xa)
  43. HIT/HITT treatment duration
    • Platelet count normalizes- transition to Coumadin/warfarin.
    • uncomplicated HIT - anticoagulant for 4-6 weeks.
    • HIT with a thrombosis (HITT)- anticoagulant 3-6 months.
  44. HIT/HITT Clinical PEARLS
    suspicious enough to send the test = STOP ALL HEPARIN- start a DTI.
Card Set
Thrombosis Hematology
Thrombosis Hematology