Heparin-induced thrombocytopenia: historical review

Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombosis (HITT), recognized as clinical entities only in the past 30 years, have become a major concern for all who work in the field of thromboembolism, its prevention, and treatment. Studies of the 1930 to 1970 era were primarily devoted to the interaction of heparin with platelets in vivo with no knowledge that such interaction could lead to serious morbidity and mortality in as many as 3-5% of patients receiving the drug. When this was recognized in the 1970s, concerns arose regarding recognition and diagnoses. Clinicians, laboratory investigators, and drug companies entered into many research collaborations. The advent of low molecular weight heparin (LMWH) and heparinoids led to studies of their interaction with the IgG antibody that was identified as the mechanism for heparin-induced thrombocytopenia of the immune type. Newer, more sensitive test systems were developed and applied to studies comparing the new low LMWHs and heparinoids. These studies showed a lower incidence of immune-mediated thrombocytopenia with LMWH. The specificity of the antibody for platelet factor 4-heparin complexes led to the development of new tests in the early 1990s. This was soon followed by experiments with antithrombin drugs such as hirudin and argatroban as replacements for heparin in the HIT-HITT syndrome. Shorter courses of heparin therapy and the use of LMWH in place of heparin had become more standard practice in the 1990s.