Krakow, G. to test the relationship between our outcome and HIT antibody seropositivity. == Results == Initially, 1021 patients enrolled between August 2006 and May 2009, follow-up was completed in December 2014. Seropositivity defined by OD > 0. 4 was common, almost 20% preoperatively, over 30% by discharge and over 60% by Day 30. Death (1. 7% within 30 days) or TEC (69 total) was more likely if seronegative (OD < 0. 4), but defining positive by OD > 1 . 0 or including an excess heparin confirmatory step resulted in equal incidence of death or TEC whether seronegative or seropositive. Incorporating the serotonin release assay for platelet activating antibodies did not alter these findings. == Conclusions == Seropositivity for anti-PF4/heparin antibodies does not increase the risk of death or thromboembolism after cardiac surgery. Screening is not indicated and seropositivity should only be interpreted in the context of clinical evidence for HIT. Keywords: Thrombocytopenia, heparin induced thrombocytopenia, thoracic surgery, thrombosis, thromboembolism == INTRODUCTION == Heparin-induced thrombocytopenia (HIT) is one of the most clinically important drug-induced complications in hospitalized patients. This paradoxical, prothrombotic response to anticoagulant therapy is an immunologic condition in which antibodies to a complex of endogenous platelet factor 4 (PF4) and exogenous heparin activate platelets, leading to aggregation, thrombocytopenia, and, potentially, thromboembolic complications [1, 2]. Treatment requires the cessation of heparin and initiation of an alternative anticoagulant, as symptomatic arterial or venous thrombosis associated with a high mortality may develop in a third to half of the patients with HIT who present with isolated thrombocytopenia [35]. Seropositivity to PF4/heparin complexes in cardiac surgery patients is common [69]. The actual incidence of HIT in patients undergoing cardiac surgery, however Rabbit Polyclonal to EDNRA , is reportedly much lower, typically 0. 5% to 1. 8% [1012]. Platelet count profiles may be helpful in determining the likelihood of HIT in a patient with thrombocytopenia following cardiopulmonary bypass surgery [13], but this has not been consistently observed [11]. This complicates the diagnosis of HIT and potentially exposes patients to hemorrhagic risks if they are treated with less familiar, non-heparin anticoagulants to treat false positive cases of HIT. However , anti-PF4/heparin antibodies in the absence of thrombocytopenia may not be entirely benign. For example , XL-888 elevated antibody levels are associated with myocardial infarction at 30 days in non-thrombocytopenic patients presenting with acute coronary syndromes [14], arteriovenous fistula thrombosis in non-diabetic hemodialysis patients [15] and increased likelihood death or prolonged hospitalization XL-888 after cardiac surgery, [16] although direct causality remains unproven. Still, heparin remains the anticoagulant of choice for over 250, 000 cardiac surgeries performed XL-888 in the US each year [17]. Up to half of these patients will develop anti-PF4/heparin antibodies, and up to 4, 500 are projected to develop HIT each year. While previous studies suggest XL-888 an independent thrombotic risk from seropositivity [18], it remains essential to critically evaluate the relationship between anti-PF4/heparin antibodies and thromboembolism in a population that reflects current clinical and laboratory practice, and is adequately powered to evaluate uncommon thromboembolic events. The overall aim of our study is to prospectively determine the time-course of anti-PF4/heparin antibody production and their relationship to thromboembolic events, from the day of surgery to 3 months after surgery, and long-term survival. These data will allow us to definitively test the hypothesis that anti-PF4/heparin antibodies are associated with thromboembolism and reduced survival after cardiac surgery. == METHODS == == Study Population == All patients undergoing cardiac surgery requiring cardiopulmonary bypass with heparin anticoagulation were eligible for study. Exclusion criteria included planned post-operative anticoagulant therapy during the hospital stay with warfarin, therapeutic dose low-molecular weight heparin, or therapeutic unfractionated heparin. The study was approved at the Institutional Review Boards at each participating site, and written informed consent was obtained from all participants. == Study Design and Measurements == The multicenter, prospective cohort study was conducted through the Rare Thrombotic Diseases Consortium (ClinicalTrials. gov #NCT00237328), and patients were enrolled at five participating centers (Duke University Medical Center, Durham Veterans Administration Medical Center, Mayo Clinic, the University of Wisconsin, and the University of North.