Two decades of research into heparin‐induced thrombocytopenia (HIT) permit a personal historical perspective on this fascinating syndrome. Previously, the frequency of HIT was unknown, although complicating thrombosis was believed to be rare and primarily arterial. The opportunity to apply a remarkable test for “HIT antibodies”—the 14C‐serotonin‐release assay (SRA)—to serial plasma samples obtained during a clinical trial of heparin thromboprophylaxis, provided insights into the peculiar nature of HIT, such as, its prothrombotic nature—including its strong association with venous thrombosis (RR = 11.6 [95%CI, 6.4–20.8; P < 0.0001); its more frequent occurrence with unfractionated versus low‐molecular‐weight heparin; the “iceberg” model, which states that among the many patients who form anti‐PF4/heparin antibodies during heparin therapy, only a minority whose antibodies evince strong platelet‐activating properties develop HIT; and the characteristic HIT timeline, whereby serum/plasma antibodies are readily detectable at or prior to the HIT‐associated platelet count fall. Applying the SRA also to patients encountered in clinical practice led to recognition of warfarin‐induced venous limb gangrene (for which HIT is a major risk factor via its extreme hypercoagulability) and delayed‐onset HIT (whereby thrombocytopenia begins or worsens following heparin discontinuation, due to the ability of HIT antibodies strongly to activate platelets even in the absence of heparin—so‐called heparin‐“independent” platelet activation). Recent concepts include the increasing recognition of HIT “overdiagnosis” (due to the low diagnostic specificity of the widely‐applied PF4‐dependent immunoassays), and the observation that HIT‐associated consumptive coagulopathy is a risk factor for treatment failure with PTT‐adjusted direct thrombin inhibitor therapy (“PTT confounding” secondary to HIT‐associated coagulopathy). Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.

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   |texte=   HITlights: A career perspective on heparin‐induced thrombocytopenia
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