Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction characterized by thrombocytopenia and a high risk for venous or arterial thrombosis.1 It is caused by heparin-dependent, platelet-activating antibodies that recognize a “self” protein, platelet factor 4 (PF4), bound to heparin. The resulting platelet activation is associated with increased thrombin generation (Figure).2 Typically, the platelet count fall begins 5 to 10 days after starting heparin, although a rapid platelet count fall can occur in a patient who has antibodies from recent heparin use.3 Remarkably, transience of HIT antibodies permits safe heparin reexposure in selected patients (for example, heart surgery patients) despite a history of HIT.3,4 Pathogenesis of HIT. HIT antibodies of IgG class bind to multimolecular complexes of platelet factor 4 (PF4) and heparin on platelet surfaces, resulting in platelet activation when the IgG molecules interact with the platelet Fc receptors. Platelet-derived microparticles are generated, which enhance coagulation reactions. In addition, HIT antibodies can activate endothelium and monocytes, exacerbating the procoagulant response. Activation of platelets and increased production of thrombin could explain the high risk of arterial and venous thrombosis in HIT. Reprinted with permission from Greinacher and Warkentin.2 A 61-year-old woman5 with Ray-naud’s phenomenon underwent mechanical aortic valve replacement for aortic insufficiency. She developed persistent vasospasm of fingers and toes after surgery that responded to warming measures. Unfractionated heparin (UFH) prophylaxis was given until postoperative day 4, and warfarin (5, 5, and 2.5 mg) was given from days 2 to 4. On day 8, the patient developed ischemic necrosis of multiple fingers and toes. The platelet count had fallen by 44% from 221×109/L (day 4) to 124×109/L (day 8), and the international normalized ratio (INR) rose to 4.3. The diagnosis of delayed-onset HIT complicated by warfarin-induced digital necrosis was supported …