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The opportunity to apply a remarkable test for \u201cHIT antibodies\u201d\u2014the <jats:sup>14<\/jats:sup>C\u2010serotonin\u2010release assay (SRA)\u2014to serial plasma samples obtained during a clinical trial of heparin thromboprophylaxis, provided insights into the peculiar nature of HIT, such as, its prothrombotic nature\u2014including its strong association with venous thrombosis (RR = 11.6 [95%CI, 6.4\u201320.8; <jats:italic>P<\/jats:italic> &lt; 0.0001); its more frequent occurrence with unfractionated versus low\u2010molecular\u2010weight heparin; the \u201ciceberg\u201d model, which states that among the many patients who form anti\u2010PF4\/heparin antibodies during heparin therapy, only a minority whose antibodies evince strong platelet\u2010activating properties develop HIT; and the characteristic HIT timeline, whereby serum\/plasma antibodies are readily detectable at or prior to the HIT\u2010associated platelet count fall. Applying the SRA also to patients encountered in clinical practice led to recognition of warfarin\u2010induced venous limb gangrene (for which HIT is a major risk factor via its extreme hypercoagulability) and delayed\u2010onset 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\u2014so\u2010called heparin\u2010\u201cindependent\u201d platelet activation). Recent concepts include the increasing recognition of HIT \u201coverdiagnosis\u201d (due to the low diagnostic specificity of the widely\u2010applied PF4\u2010dependent immunoassays), and the observation that HIT\u2010associated consumptive coagulopathy is a risk factor for treatment failure with PTT\u2010adjusted direct thrombin inhibitor therapy (\u201cPTT confounding\u201d secondary to HIT\u2010associated coagulopathy). Am. J. Hematol. 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.23127","type":"journal-article","created":{"date-parts":[[2012,1,19]],"date-time":"2012-01-19T14:28:07Z","timestamp":1326983287000},"source":"Crossref","is-referenced-by-count":38,"title":["HITlights: A career perspective on heparin\u2010induced thrombocytopenia"],"prefix":"10.1002","volume":"87","author":[{"given":"Theodore E.","family":"Warkentin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,2,24]]},"reference":[{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.me.40.020189.000335"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-3019(83)90027-7"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V67.1.27.27"},{"key":"e_1_2_11_5_2","first-page":"600","article-title":"Heparin\u2010associated thrombocytopenia and 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