Heparin-Induced Thrombocytopenia (HIT) (Last Updated - 3/29/2005)

-dx. requires either:
     A) new onset platelet count < 150,000 or
     B) 50% decrease of platelet count from pre-tx values

-Incidence:
     -occurs in ~3% of pts. (less in LMWH's)
     -1/3 of these 3% (overall 1%) will develop thrombotic complications
     -usually arises 5-10 days after initiation of heparin tx.

-Mechanism:
     -heparin triggers IgG & IgM Ab response (if given for > 4 days)
     -the Ab response is triggered by the heparin/PF4-complex on the platelet surface
     -the Ab's bind to the heparin/PF4-complex and:
          A) Activates the platelet --> platelet aggregation & premature removal from circulation
          B) Induces increased PF4 release --> pro-coagulation
          C) Induces prothrombin (Factor II) to thrombin (Factor IIa) activation --> pro-coagulation
     -leading to thrombosis & thrombocytopenia --> major clinical risks of HIT

-Diagnosis:
     -HIT-Ab level

-Tx:
     -d/c heparin immediately if pt. develops clinical signs (Ex.) thrombosis or thrombocytopenia) > 4 days after heparin initiation
     -thrombotic complications may still occur even after drug has been d/c'd --> must anti-coagulate w/ another drug:
          A) Direct Thrombin Inhibitors:
               1) Argatroban
               2) Bivalirudin (Angiomax)
               3) Lepirudin (Refludan)
          B) Non-Heparin Glycosaminoglycan Anti-Coagulants:
               1) Danaparoid (Orgaran)

-AVOID in pts. w/ HIT (possible cross-reactivity w/ heparin):
     1) LMWH's:
          -very often cross-react w/ heparin
     2) Warfarin (Coumadin):
          -may cause venous limb gangrene in pts. w/ HIT

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References:

Goodman & Gilman's: The Pharmacologic Basis Of Therapeutics - 10th Edition - 2001. Chapter 55.