Thrombosis in Suspected Heparin-induced Thrombocytopenia Occurs More Often with High Antibody Levels
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
© 2012 Elsevier Inc. All rights reserved.

