1. Sisson, Evan M. PharmD, MHA, CDE

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Heparin-induced thrombocytopenia (HIT) has been reported to occur in 0.3% to 3% of patients receiving heparin, usually within five to 14 days of exposure, but onset can occur as long as four weeks after termination of therapy. HIT is thought of as an autoimmune disorder precipitated by the binding of heparin to platelet factor 4 (PF4). Antibodies to the heparin-PF4 complex activate platelets, resulting in their aggregation. The aggregated platelets are removed prematurely from the circulation, leading to thrombocytopenia (at platelet counts either less than 150 x 109/L or half of the baseline value). Platelet aggregation also initiates clot formation, leading to a 50% risk of venous or arterial thrombosis, which is associated with serious complications, including pulmonary embolism, ischemic stroke, myocardial infarction, skin necrosis, and limb ischemia and has a 17% to 30% mortality rate.


The treatment of HIT entails avoiding exposure to all heparin administration (including heparin flushes) and initiating nonheparin anticoagulation with one of the direct thrombin inhibitors, argatroban, lepirudin (Refludan), and bivalirudin (Angiomax). These reduce the risk of thrombosis significantly. (Patients with documented HIT should have their medical records clearly marked to prevent exposure to all heparin products. Although low-molecular-weight heparin [LMWH] is associated with a lower incidence of HIT, antibodies to the heparin-PF4 complex can cross-react with LMWH products like enoxaparin [Lovenox], precipitating thrombosis or severe thrombocytopenia.) In addition, warfarin dosed to maintain an international normalized ratio (INR) of 2 to 3 can be administered to avert thrombosis but only after the platelet count rises above 150 x 109/L. Also, because warfarin therapy raises thrombin levels, its initiation must overlap for at least five days with administration of an agent that inhibits the action of thrombin or its generation at a therapeutic INR for two successive days.


Because HIT can be so serious, the Food and Drug Administration has required revisions of heparin package inserts advising providers that HIT can occur several weeks after heparin therapy has ended. The possibility of HIT is greatest in female postsurgical patients receiving unfractionated heparin for more than four days. Nurses should be aware of the symptoms of thrombosis (signs of cardiac, respiratory, neurologic, or renal dysfunction), carefully observe for them in patients at highest risk for HIT, and inform patients at the time of discharge of the signs and symptoms of the condition and instruct them to either contact the physician or go to an ED should they emerge.


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