title: How I diagnose and manage HIT.
abstract: Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4)/polyanion complexes. Platelet activation assays, such as the serotonin-release assay, are superior to PF4-dependent immunoassays in discerning which heparin-induced antibodies are clinically relevant. When HIT is strongly suspected, standard practice includes substituting heparin with an alternative anticoagulant; the 2 US-approved agents are the direct thrombin inhibitors (DTIs) lepirudin and argatroban, which are "niche" agents used only to manage HIT. However, only ~ 10% of patients who undergo serological investigation for HIT actually have this diagnosis. Indeed, depending on the clinical setting, only 10%-50% of patients with positive PF4-dependent immunoassays have platelet-activating antibodies. Therefore, overdiagnosis of HIT can be minimized by insisting that a positive platelet activation assay be required for definitive diagnosis of HIT. For these reasons, a management strategy that considers the real possibility of non-HIT thrombocytopenia is warranted. One approach that I suggest is to administer an indirect, antithrombin (AT)-dependent factor Xa inhibitor (danaparoid or fondaparinux) based upon the following rationale: (1) effectiveness in treating and preventing HIT-associated thrombosis; (2) effectiveness in treating and preventing thrombosis in diverse non-HIT situations; (3) both prophylactic- and therapeutic-dose protocols exist, permitting dosing appropriate for the clinical situation; (4) body weight-adjusted dosing protocols and availability of specific anti-factor Xa monitoring reduce risk of under- or overdosing (as can occur with partial thromboplastin time [PTT]-adjusted DTI therapy); (5) their long half-lives reduce risk of rebound hypercoagulability; (6) easy coumarin overlap; and (7) relatively low cost.
authors.affiliation: Department of Pathology and Molecular Medicine, Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada. twarken@mcmaster.ca
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
mesh_terms: D000906:Antibodies / Q000276:immunology; D000991:Antithrombins / Q000627:therapeutic use; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D015539:Platelet Activation / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D000906:Antibodies; D000991:Antithrombins; D006493:Heparin