title: HIT paradigms and paradoxes.
abstract: The current major problem with HIT is its overdiagnosis. This concept follows from the HIT central paradigm: HIT is caused by a subset of antibodies against platelet factor 4 (PF4)/heparin complexes that have strong platelet-activating properties. Prospective studies show that only a minority of sera containing such antibodies exhibit platelet-activating properties. Ironically, the earliest tests for HIT--platelet activation assays--remain today the most diagnostically useful, particularly the washed platelet assays. But the wider application of PF4-dependent immunoassays, and their much greater sensitivity for the larger subset of non-platelet-activating (and non-HIT-inducing) antibodies, has resulted in HIT overdiagnosis in many centres. Studies of anti-PF4/heparin immunization in diverse clinical situations have provided insights into the factors that influence the HIT immune response. Besides the conundrum of anticoagulant-induced thrombosis (including its potentiation of coumarin-induced microthrombosis), HIT evinces numerous other paradoxes: (i) it is a platelet-activating disorder with venous thrombosis as its predominant clinical manifestation; (ii) 'delayed-onset' (or 'autoimmune') HIT can lead to dramatic worsening of HIT-associated thrombosis despite cessation of heparin; (iii) partial thromboplastin time (PTT) monitoring of direct thrombin inhibitor treatment - and confounding of PTT monitoring by HIT-associated consumptive coagulopathy - infers that the worst subset of HIT patients may fail this therapeutic approach; (iv) the highly sulfated pentasaccharide anticoagulant, fondaparinux, can (rarely) cause HIT yet appears to be an effective treatment for this disorder; and (v) the transience of the HIT immune response means that many patients with previous HIT can safely receive future heparin.
authors.affiliation: Department of Pathology and Molecular Medicine, Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: T E
authors.initials: TE
authors.lastname: Warkentin
mesh_terms: D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D007118:Immunoassay; D015539:Platelet Activation; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced*
chemical_list: D006493:Heparin