Heparin-induced Thrombocytopenia (HIT)(1. Systemic Complications Neurosurgeons need to Know,<SPECIAL ISSUES>Stroke as a Systemic Vascular Disease)

Abstract

An anticoagulant turns procoagulant. This is the fundamental paradox of heparin-induced thrombocytopenia (HIT), an immune-mediated, life-threatening side effect of heparin therapy. Antibodies against complexes of platelet factor 4 and heparin induced by heparin administration, when they have the high levels of platelet-activating properties (HIT antibodies), are the major cause of HIT. HIT antibodies stimulate platelets and endothelial cells resulting in thrombocytopenia, increased thrombin generation, and associated venous and arterial thrombosis. HIT typically occurs 5 to 14 days after heparin administration (typical-onset HIT). HIT antibodies are transient but can be detected for about 100 days after cessation of heparin treatment. Thus, some patients develop HIT several days after discontinuing heparin (delayed-onset HIT) or soon after the re-administration of heparin (rapid-onset HIT), that is caused by the residual circulating HIT antibodies that resulted from the recent heparin treatment. HIT should be considered as a clinicopathologic syndrome and must be diagnosed through a combination of clinical pretest probability (e.g. the 4T's scoring system) and the detection of HIT antibodies by a serological assay. Several clinical research studies performed in Western countries have revealed that the prevalence of HIT is 0.5 to 5%, which varies depending on the clinical settings. HIT is life threatening, especially when unrecognized or untreated. Thromboembolic events can occur in 25 to 50% of HIT patients, and the thombotic death rate can reach to about 5%. All heparin administration including heparin flushes should be discontinued in patients strongly suspected of having HIT and substituted with a thrombin inhibitor. Recognition of HIT has improved in Japan since manufacturers' prescribing information (package insert) on heparin was revised to mention HIT in April, 2006. In addition, argatroban, a direct thrombin inhibitor, was recently approved by Japanese regulators in July, 2008 as the first drug for the treatment of HIT, based on the results of a multicenter, non-randomized, open-label trial performed at 20 institutes. Several retrospective studies and a multicenter, prospective cohort study suggest lower incidences of HIT in Japan than what is diagnosed in Western countries, probably due to ethnic factors and/or different clinical practices. Based on these results, we will seek to establish Japanese guidelines for the diagnosis and treatment of HIT.