The association of anti-platelet factor 4/heparin antibodies with early and delayed thromboembolism after cardiac surgery

I. J. Welsby, E. F. Krakow, J. A. Heit, E. C. Williams, G. M. Arepally, S. Bar-Yosef, D. F. Kong, S. Martinelli, I. Dhakal, W. W. Liu, J. Krischer, T. L. Ortel

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4 Scopus citations


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. Summary: 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. Trial registration: Duke IRB Protocol #00010736

Original languageEnglish (US)
JournalJournal of Thrombosis and Haemostasis
StateAccepted/In press - 2016



  • Heparin-induced thrombocytopenia
  • Thoracic surgery
  • Thrombocytopenia
  • Thromboembolism
  • Thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

Welsby, I. J., Krakow, E. F., Heit, J. A., Williams, E. C., Arepally, G. M., Bar-Yosef, S., Kong, D. F., Martinelli, S., Dhakal, I., Liu, W. W., Krischer, J., & Ortel, T. L. (Accepted/In press). The association of anti-platelet factor 4/heparin antibodies with early and delayed thromboembolism after cardiac surgery. Journal of Thrombosis and Haemostasis.