Venous thromboembolism in heparin-induced thrombocytopenia.
Deep-vein thrombosis (DVT) and pulmonary embolism are among the most common complications of heparin-induced thrombocytopenia (HIT), an antibody-mediated adverse effect of heparin that leads paradoxically to in vivo activation of platelets and the coagulation system. Inappropriate treatment of HIT-associated DVT with warfarin can cause the DVT to progress to limb gangrene: this results from impaired ability of the protein C natural anticoagulant pathway to down-regulate thrombin generation, thus leading to microvascular thrombosis and tissue necrosis. Appreciation of the importance of coagulation system activation in HIT provides a rationale for treatments that reduce thrombin generation, either via inhibiting factor Xa (danaparoid) or via inhibiting thrombin directly (lepirudin). Clinicians should know how to distinguish HIT from other thrombocytopenic disorders: for example, thrombocytopenia associated with pulmonary embolism can mimic HIT (pseudo-HIT), and acute dyspnea that can mimic acute pulmonary embolism can result from acute in vivo platelet activation in a patient with HIT antibodies who receives heparin bolus therapy (pseudo-pulmonary embolism).
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. twarken@fhs.mcmaster.ca
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D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D002809:Chondroitin Sulfates / Q000627:therapeutic use; D003871:Dermatan Sulfate / Q000627:therapeutic use; D004338:Drug Combinations; D005734:Gangrene / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects*; D006497:Heparan Sulfate / Q000627:therapeutic use; D006801:Humans; D007866:Leg / Q000098:blood supply; D011655:Pulmonary Embolism / Q000209:etiology*; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000150:complications*; D020246:Venous Thrombosis / Q000209:etiology*; D014859:Warfarin / Q000009:adverse effects
D000925:Anticoagulants; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D004338:Drug Combinations; D006493:Heparin; D006497:Heparan Sulfate; D014859:Warfarin; C035838:danaparoid