Role of anti-PF4/heparin antibodies in recurrent thrombotic events after acute coronary syndromes.

Abstract

We postulated that patients with recent acute coronary syndromes and antibodies to the platelet factor 4/heparin complex would have an increased risk of myocardial infarction (MI), even in the absence of thrombocytopenia. We analyzed sera from patients enrolled in the placebo/unfractionated heparin arm of the GUSTO IV-ACS trial who had a high likelihood of prior heparin exposure. We selected 109 patients without thrombocytopenia with the 30-day primary endpoint (death, MI, or revascularization) and 109 age-, gender-, and race-matched controls who did not achieve the primary endpoint. Twenty-three of 218 patients (10.6%) had anti-PF4/heparin antibodies. Patients with anti-PF4/heparin were more likely to have death or MI (30.4% vs. 11.3%, p = 0.011) or MI (21.7% vs. 6.2%, p = 0.008) than patients who were negative for the antibody. Antibody-positive patients had higher levels of sVCAM-1 (892 +/- 263 microg/L vs. 780 +/- 228 microg/L; p = 0.04) and sICAM-1 (246 +/- 50 microg/L vs. 222 +/- 71 microg/L; p = 0.02) than antibody-negative patients. In a multiple logistic regression model that included inflammatory markers and clinical risk factors, antibodies to PF4/heparin were a strong predictor of 30-day MI (odds ratio, 9.0; 95% confidence intervals, 2.1 to 38.6; p < 0.01), with IL-6 being the only other predictor (odds ratio, 1.1; 95% confidence intervals, 1.0 to 1.2; p = 0.03). Antibodies to the platelet factor 4/heparin complex are a novel, independent predictor of MI at 30 days in patients presenting with acute coronary ischemic syndromes. Antibodies to PF4/heparin are a stronger predictor of MI than clinical characteristics or inflammation markers.

• Authors: Mary Ann Mascelli, Efthymios N Deliargyris, Lakshmi V Damaraju, Elliot S Barnathan, David C Sane
• Journal: Seminars in thrombosis and hemostasis (Semin Thromb Hemost) Vol. 30 Issue 3 Pg. 347-50 (Jun 2004) ISSN: 0094-6176 [Print] United States
• PMID: 15282657 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antibodies
• Antibodies, Monoclonal
• Anticoagulants
• Immunoglobulin Fab Fragments
• Placebos
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Platelet Factor 4
• Heparin
• Abciximab

Topics

• Abciximab
• Acute Disease
• Antibodies (chemistry)
• Antibodies, Monoclonal (therapeutic use)
• Anticoagulants (therapeutic use)
• Blood Platelets (immunology)
• Clinical Trials as Topic
• Female
• Heart Diseases (complications, pathology)
• Heparin (chemistry, immunology)
• Humans
• Immunoglobulin Fab Fragments (therapeutic use)
• Inflammation
• Intercellular Adhesion Molecule-1 (blood)
• Male
• Myocardial Infarction
• Odds Ratio
• Placebos
• Platelet Factor 4 (immunology)
• Recurrence
• Thrombosis (etiology)
• Time Factors
• Vascular Cell Adhesion Molecule-1 (blood)