Incidence of heparin-PF4 complex antibody formation and heparin-induced thrombocytopenia in acute coronary syndrome

A multicenter prospective study on the rate of seroconversion of antibodies to heparin-PF4 complexes (heparin-induced thrombocytopenia [HIT] antibodies) during and after heparin treatment for 4 weeks was carried out in Japanese patients with acute coronary syndrome (ACS). A total of 254 ACS patients treated with heparin were enrolled consecutively from 12 facilities of cardiology. Two patients with preexisting HIT antibodies were excluded from the analysis. The total seroconversion rate for four weeks during and after heparin treatment was 8.7% (n=22, 95% confidence interval [CI]: 5.9-13.1), including values of 3.2% (n=8) at the end of heparin infusion and 5.5% (n=14) at 4 weeks. Among 22 seroconverted patients, four developed HIT and two of the four had the complication of thrombosis. The incidence of HIT was 1.6% (n=4, 95% CI: 0.04-3.1). The risk for thromboembolic development was higher in the seroconverted patients (odds ratio, 17.4, 95% CI: 5.2-58.4, p<0.0001) than nonconverted patients. An analysis of factors affecting the seroconversion rate was carried out. The seroconversion rate for ACS patients who underwent percutaneous coronary intervention (PCI; n=163) was 12.3%, significantly higher than the 2.3% in patients who did not undergo PCI (n=89), leading to an odds ratio of 6.1 (95% CI: 1.4-26.7, p=0.009). A significant odds ratio was obtained for each factor affecting the seroconversion: 3.5 (95% CI: 1.3-9.9, p=0.014) for more than 5 days of heparin infusion, 3.0 (95% CI: 1.2-7.6, p=0.035) for a thrombotic history and 2.7 (95% CI: 1.1-6.8, p=0.039) for hyperlipidemia. No other factor, including age or diabetes mellitus, contributed to the seroconversion. Therefore, PCI, duration of heparin treatment and thrombotic history facilitated the seroconversion in ACS patients. PCI patients treated for more than 5 days with heparin showed a maximal seroconversion rate of 18.3% (95% CI: 13.8-22.2). This high rate in PCI patients did not interact with age, type of underlying disease of unstable angina or myocardial infarction or thrombotic history. In conclusion, ACS patients demonstrating seroconversion are at risk of thromboembolic development due to the likelihood of immunomediated endothelial dysfunction. The increase in the rate of seroconversion in ACS patients would be affected by factors such as PCI with mechanical stress, longer duration of heparin treatment, thrombotic history and presence of hyperlipidemia. If PCI is undertaken with heparin anticoagulation for more than 5 days, seroconversion would easily occur, and the seroconverted patients could subsequently suffer from HIT.