Heparin-Induced Thrombocytopenia: An Update

Abstract

Heparin-induced thrombocytopenia (HIT) is an immune response to heparin that can progress to severe thrombosis, amputation, and in some cases death. The diagnosis and treatment of HIT is complex, but needs to be considered in the clinical management of patients exposed to heparin due to its serious outcomes. Early diagnosis based on a comprehensive interpretation of clinical and laboratory information improves clinical outcomes. This begins with careful monitoring for thrombocytopenia and thrombosis during and for at least 5 to 10 days after heparin treatment of any dose and duration. Appropriate use and knowledgeable interpretation of laboratory tests for HIT are important, as these vary in sensitivity and specificity, with each type providing unique information. Clinical management of patients with HIT is with a non-heparin anticoagulant such as a direct thrombin inhibitor or danaparoid followed by a vitamin K antagonist for long-term treatment. Important drug-specific limitations, dosing, and monitoring guidelines must be respected for patient safety. There continues to be new developments in the field of HIT: laboratory testing, clinical scoring systems, and available new anticoagulants. Research and clinical studies will continue to address the unresolved issues and unmet clinical needs associated with HIT. This review summarizes the clinical management of HIT.

Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis

“…Heparin-induced thrombocytopenia and thrombosis (HIT), a major cause of morbidity and mortality in patients treated with heparin, [1][2][3] is caused by immunoglobulins ("HIT antibodies") that recognize platelet factor 4 (PF4) in a complex with heparin.…”

“…7,8 It is widely thought that HIT antibodies bind to heparin/ PF4 complexes formed on or near the platelet membrane when heparin is infused, and that the resulting immune complexes induce platelet activation, release of platelet granule contents, and formation of procoagulant microparticles when immunoglobulin G (IgG) Fc domains engage platelet FcgRIIa (CD32) receptors. 3,9 The half-life of unfractionated heparin administered intravenously is only about 2 hours, 10 yet thrombotic risk persists for at least several weeks after an episode of HIT, 7,11,12 and occasional patients with "delayed HIT" develop acute thrombocytopenia and thrombosis a week or more after their last exposure to heparin. [13][14][15][16] These manifestations of heparin sensitivity, occurring long after heparin has been cleared from the circulation, are not well understood.…”

A Novel PF4-Dependent Platelet Activation Assay Identifies Patients Likely to Have Heparin-Induced Thrombocytopenia/Thrombosis

“…[1][2][3] HIT is characterized by thrombocytopenia, usually beginning 5 to 10 days after starting heparin therapy. Although thrombocytopenia in patients receiving heparin is, in itself, generally mild, it can provide an important clue that a patient is developing HIT and is at risk for thromboembolic complications.…”

Pharmacotherapy of heparin-induced thrombocytopenia: Therapeutic options and challenges in the clinical practices

“…A heparin source such as bovine lung is more immunogenic than those produced from porcine intestine, 15 and the risk of HIT rises with the length and volume of exposure to heparin as well as the route of administration, 16 and more likely with intravenous heparin than subcutaneous administration. [17][18][19] Nevertheless, HIT can develop from any heparin exposure, including incidental amounts from heparin flushes or heparin-coated devices. 20,21 Although HIT is more common in patients receiving UFH than in those treated with LMWH, 22,23 it is very important to note that HIT that is developing in patients receiving UFH frequently cross-reacts with the use of LMWH.…”