Thrombotic events in patients with antiplatelet factor 4/heparin antibodies

BACKGROUND: Antibodies to the heparin/platelet factor 4(PF4)complex are linked to the pathogenesis of heparin-induced thrombocytopenia type II, and to the thrombotic complications associated with this syndrome. We investigated the long-term relationship between antibody concentration and thrombosis. METHODS: Two-hundred and fifty patients who had been treated with unfractionated heparin as part of cardiac surgery management were included in the study. Immunoassay ELISA test was used to detect the presence and the plasma concentration of heparin-PF4 antibodies (as optical density value, O.D.). Follow-up lasted one year and new thrombotic events (myocardial infarction, stroke, pulmonary embolism), and death from any cause, were evaluated. RESULTS: Seventy-nine of 250 patients (31.6%) developed anti-PF4/heparin antibodies after cardiac surgery. Nadir platelet count was significantly lower in patients who developed antibody positivity (82,000+/-31,000/mm(3) versus 105,000+/-52,000/mm(3),P<0.001). At follow up, patients with anti-PF4/heparin antibodies were more likely to die or develop myocardial infarction (25.3% versus 10.5%, P<0.001), pulmonary embolism (20.2% versus 5.8%, P<0.001), or stroke (12.6% versus 5.8%, P<0.001), than patients who were antibody-negative. Patients were categorized in quintiles of antibody concentration according to the O.D. The risk of developing thrombotic events markedly increased with increasing quintile of O.D., with the highest group showing an OR of 7.68(4.04-9.20)(P<0.001). CONCLUSIONS: Patients who develop antibodies to the PF4-heparin complex have a significantly higher rate of thrombotic events during a one year follow-up than those who lack these antibodies; within this group the risk of developing thrombosis increases with increasing plasma concentration of antibodies.