Hit antibody syndrome is a serious immune-mediated reaction that results in paradoxical thrombosis despite falling platelet counts.  It occurs in 1-3 % of patients exposed to unfractionated heparin.  Suspect Heparin-induced thrombocytopenia (HIT) when platelet count falls below 100,000 or with a greater than 50% drop from baseline.  HIT is an antibody mediated process that occurs most commonly in surgical patients and patients with underlying cancer and typically occurs 5-14 days into heparin-based treatment.  The disorder can occur earlier if there is previous heparin exposure in the preceding 3 months.  HIT is more common in women than men and occurs but to a lesser extent with fractionated heparin.  Venous thrombosis is more common than arterial thrombosis.  Mechanism of action is a negatively charged heparin molecule combining with a positively charged Platelet Factor 4.  This union becomes antigenic and stimulates IgG production, which binds with the complex, stimulating more platelet activation, more Platelet Factor 4 release and a self-ampifying cycle occurs, resulting in platelet consumption, resulting in thrombocytopenia, and massive thrombin generation.  The thrombin generation is initiated by the release of platelet microparticles, which are prothrombotic and bind clotting factors on their surface, promoting thrombin generation and clotting.  Confirmation with a Serotonin Release Assay is critical, but since this is a radio-isotope test, results may take at least several days.  Treatment should begin prior to confirmatory testing if the index of suspicion is moderate to high.  Treatment includes stopping all heparin, avoiding platelet transfusions, and giving an alternative anticoagulant to protect against or treat clotting.  First line agents are Argatroban (IV), Bivalirudin (IV), or Fondaparinux (SubQ).  Oral agents can be used once platelets rise above 150,000.  Avoidance of Warfarin until platelets normalize is important as Warfarin may promote skin necrosis in this setting.