The American Journal of Medicine
Volume 125, Issue 1 , Pages 44-49, January 2012

Thrombosis in Suspected Heparin-induced Thrombocytopenia Occurs More Often with High Antibody Levels

  • Steven Baroletti, PharmD, MBA

      Affiliations

    • Department of Pharmacy, Metrowest Medical Center, Framingham, Mass
  • ,
  • Shelley Hurwitz, PhD

      Affiliations

    • Center for Clinical Investigation, Brigham and Women's Hospital, Boston, Mass
  • ,
  • Nicole A.S. Conti, PharmD

      Affiliations

    • Department of Pharmacy, Brigham and Women's Hospital, Boston, Mass
  • ,
  • John Fanikos, RPh, MBA

      Affiliations

    • Department of Pharmacy, Brigham and Women's Hospital, Boston, Mass
  • ,
  • Gregory Piazza, MD

      Affiliations

    • Venous Thromboembolism Research Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
  • ,
  • Samuel Z. Goldhaber, MD

      Affiliations

    • Venous Thromboembolism Research Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
    • Corresponding Author InformationRequests for reprints should be addressed to Samuel Z. Goldhaber, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115

published online 09 November 2011.

Abstract 

Objective

The study objective was to determine whether higher antiplatelet factor 4 (PF4)/heparin antibody levels using an enzyme-linked immunosorbent assay are associated with more frequent thrombotic events in patients with clinically suspected heparin-induced thrombocytopenia. Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction. An enzyme-linked immunosorbent assay detects anti-PF4/heparin antibodies to support a suspected clinical diagnosis of heparin-induced thrombocytopenia. The utility of quantitative enzyme-linked immunosorbent assay results is uncertain.

Methods

Our single-centered study evaluated quantitative anti-PF4/heparin antibody levels using an enzyme-linked immunosorbent assay in consecutive hospitalized patients with a clinical suspicion of heparin-induced thrombocytopenia and positive anti-PF4/heparin antibody levels between July 2003 and December 2006.

Results

Overall, anti-PF4/heparin antibody values were available for 318 patients with clinically suspected heparin-induced thrombocytopenia. The median level was 0.85 optical density units (range 0.31-4.0). The overall rate of arterial or venous thrombosis was 23.3%. A 1-unit increase in anti-PF4/heparin antibody level was associated with an approximate doubling in the odds of thrombosis by 30 days (odds ratio, 1.9; 95% confidence interval, 1.5-2.6; P=.0001). The proportion of patients with pulmonary embolism increased with higher anti-PF4/heparin antibody levels.

Conclusion

Higher levels of anti-PF4/heparin antibody are associated with increased thrombosis risk among patients with clinically suspected heparin-induced thrombocytopenia and might have clinical utility for prediction of true heparin-induced thrombocytopenia and the development of thrombosis.

Keywords:  Antiplatelet factor 4 antibody , Deep vein thrombosis , Enzyme-linked immunosorbent assay , Heparin-induced thrombocytopenia , Low-molecular-weight heparin , Pulmonary embolism , Unfractionated heparin , Venous thromboembolism

 

 Funding: This study was investigator-initiated and had no outside source of funding.

 Conflict of Interest: The authors of this article have disclosed the following industry relationships: JF served as a consultant/advisory board participant for Bristol-Myers Squibb and Baxter Healthcare. SZG receives research funds from Sanofi-Aventis, Eisai, Bristol-Myers Squibb, Johnson and Johnson, EKOS, and Boehringer-Ingelheim and is a consultant for Sanofi-Aventis, Eisai, Bristol-Myers Squibb, EKOS, Portola, Merck, and Boehringer-Ingelheim. GP is supported by a Research Career Development Award (K12 HL083786) from the National Heart, Lung, and Blood Institute. SB, NASC, and SH have no conflicts to disclose.

 Authorship: All authors had access to the data and played a role in writing this manuscript.

PII: S0002-9343(11)00630-9

doi:10.1016/j.amjmed.2011.06.025

The American Journal of Medicine
Volume 125, Issue 1 , Pages 44-49, January 2012