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.