title: The association of anti-platelet factor 4/heparin antibodies with early and delayed thromboembolism after cardiac surgery.
abstract: Essentials We evaluated antibody status, thromboembolism and survival after cardiac surgery. Positive antibody tests are common - over 50% are seropositive at 30 days. Seropositivity did not increase thromboembolism or impair survival after cardiac surgery. Results show heparin induced thrombocytopenia antibody screening after surgery is not warranted.
  
  
  
  Background Heparin-induced thrombocytopenia (HIT) is a prothrombotic response to heparin therapy with platelet-activating, anti-platelet factor 4 (PF4)/heparin antibodies leading to thrombocytopenia associated with thromboembolism. Objective We tested the hypothesis that anti-PF4/heparin antibodies are associated with thromboembolism after cardiac surgery. Methods This multicenter, prospective cohort study collected laboratory and clinical data up to 30 days after surgery and longer-term clinical follow-up data. The primary outcome variable combined new arterial or venous thromboembolic complications (TECs) with all-cause death until 90 days after surgery. Laboratory analyses included platelet counts and anti-PF4/heparin antibody titers (GTI ELISA), with a confirmatory excess heparin step and serotonin release assay. Chi-square testing was used to test the relationship between our outcome and HIT antibody seropositivity. Results Initially, 1021 patients were enrolled between August 2006 and May 2009, and follow-up was completed in December 2014. Seropositivity defined by OD > 0.4 was common, being almost 20% preoperatively, > 30% by discharge, and > 60% by day 30. Death (1.7% within 30 days) or TECs (69 in total) were more likely if the partient was seronegative (OD < 0.4), but positivity defined by OD > 1.0 or including an excess heparin confirmatory step resulted in equal incidence of death or TECs, whether the patient was 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.
  
  
  
  Duke IRB Protocol #00010736.
authors.affiliation: Department of Anesthesiology and Critical Care, Durham, NC, USA.
authors.forename: I J
authors.initials: IJ
authors.lastname: Welsby
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: E F
authors.initials: EF
authors.lastname: Krakow
authors.affiliation: Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Durham, NC, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Heit
authors.affiliation: Department of Medicine, Division of Hematology, University of Wisconsin, Durham, NC, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Williams
authors.affiliation: Department of Medicine, Division of Hematology, Duke University Medical Center, Durham, NC, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Arepally
authors.affiliation: Department of Anesthesiology, Durham VA Medical Center, Durham, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bar-Yosef
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Kong
authors.affiliation: Department of Anesthesiology, University of North Carolina, Durham, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Martinelli
authors.affiliation: Department of Biostatistics & Bioinformatics, Duke University Medical Center, Durham, NC, USA.
authors.forename: I
authors.initials: I
authors.lastname: Dhakal
authors.affiliation: Department of Biostatistics & Bioinformatics, Duke University Medical Center, Durham, NC, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Liu
authors.affiliation: Pediatric Epidemiology Center, University of South Florida Morsani College of Medicine, Durham, NC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Krischer
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Ortel
mesh_terms: D000368:Aged; D000906:Antibodies / Q000097:blood; D000925:Anticoagulants / Q000009:adverse effects; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000276:immunology*; D011446:Prospective Studies; D018401:Sample Size; D013921:Thrombocytopenia / Q000139:chemically induced*; D013923:Thromboembolism / Q000097:blood / Q000209:etiology* / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D010978:Platelet Factor 4; D006493:Heparin
keywords: heparin-induced thrombocytopenia; thoracic surgery; thrombocytopenia; thromboembolism; thrombosis