Anti-platelet factor 4/heparin antibodies: an independent predictor of 30-day myocardial infarction after acute coronary ischemic syndromes

Background— We postulated that antibodies to platelet factor 4/heparin complex might contribute to recurrent ischemic events in patients with acute coronary syndrome. Methods and Results— We analyzed serum from patients enrolled in the placebo/unfractionated heparin arm of the GUSTO IV-ACS trial who had high likelihood of prior heparin exposure. We selected 109 patients without thrombocytopenia with the 30-day primary end point (death, myocardial infarction [MI], or revascularization) and 109 age-, gender-, and race-matched controls who did not achieve the primary end point. An ELISA for anti-platelet factor 4/heparin antibodies was performed using 48-hour serum samples. The analyses were done by blinded investigators, and the results were correlated with clinical outcomes. Twenty-three of 218 patients (10.6%) had anti-PF4/heparin antibodies. Patients with anti-PF4/heparin antibodies were more likely to have death or MI (30.4% versus 11.3%, P =0.011) or MI (21.7% versus 6.2%, P =0.008) than patients who were negative for the antibody. After multiple logistic regression analysis, anti-PF4/heparin antibodies remained a predictor of 30-day death or MI (odds ratio, 4.0; 95% CI, 1.4 to 11.3; P =0.0093) and MI (odds ratio, 4.6; 95% CI, 1.4 to 15.0; P =0.0108). The antibody was not associated with the composite end point (death, MI, or revascularization) or with death or revascularization alone. Conclusions— Antibodies to the platelet factor 4/heparin complex are a novel, independent predictor of myocardial infarction at 30 days in patients presenting with acute coronary ischemic syndromes. This finding may explain the previous association between thrombocytopenia and adverse events in patients with acute coronary syndrome and may have important implications for the choice of anticoagulant regimens.