Heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is not only a common but also a potentially serious drug adverse effect. Unlike other drug-induced thrombocytopenias, HIT does not usually cause bleeding, but instead causes thrombosis. Thrombosis in HIT can lead to limb gangrene (requiring leg amputation) or even death. HIT is mediated by an antibody that recognizes an epitope on the platelet factor 4 (PF4)-heparin complex. The antibody-PF4-heparin complex binds to FcgammaRII receptors on the platelet surface and cross-links the receptors. This induces intense platelet activation and platelet aggregation, and simultaneously activates blood-coagulation pathways. These changes are probably the basis of the thrombotic events in HIT. Diagnosis of HIT should be made mainly on clinical criteria but should be confirmed whenever possible by laboratory tests, particularly in patients with comorbid conditions, in whom the diagnosis of HIT cannot be made with certainty without testing. The tests for HIT antibodies are either immunoassays (e.g. ELISA), or functional tests, (e.g. 14C-serotonin release assay). Once a clinical diagnosis of HIT is made, heparin should be ceased immediately and treatment with an alternative anticoagulant (such as danaparoid, r-hirudin or argatroban) commenced. This should continue for at least 5 days unless the diagnosis of HIT is subsequently proven to be incorrect. Warfarin should also be commenced when the patient is clinically stable and thrombosis is under control. There should be an overlap of a few days between warfarin and the alternative anticoagulant therapy.
Chong
B H
BH
Department of Medicine, St. George Clinical School, Sydney, NSW, Australia. beng.chong@unsw.edu.au
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000378:metabolism; D000939:Epitopes; D006493:Heparin / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D007118:Immunoassay; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D013921:Thrombocytopenia / Q000175:diagnosis* / Q000209:etiology* / Q000628:therapy; D013927:Thrombosis / Q000175:diagnosis / Q000209:etiology
D000925:Anticoagulants; D000939:Epitopes; D006493:Heparin