Antibodies to the Platelet Factor 4-Heparin Complex and Mortality in Chronic Hemodialysis Patients.

Abstract

Background: Heparin-induced thrombocytopenia is a serious complication of heparin therapy that can lead to thromboembolism, cardiovascular events or death. Patients with this disorder develop antibodies to the platelet factor 4-heparin (PF4-H) complex. Hemodialysis patients are repeatedly exposed to heparin and are at risk for developing PF4-H antibodies. The clinical impact of asymptomatic PF4-H antibodies in patients on chronic hemodialysis is not known.Objective: To determine the association between asymptomatic PF4-H antibodies and mortality in a cohort of chronic hemodialysis patients repeatedly exposed to heparin.Methods: Pre-dialysis blood samples were drawn from 419 asymptomatic patients. All patients received unfractionated heparin (Baxter) while on dialysis. All samples were screened for PF4-H antibodies using an ELISA assay (GTI PF4 Enhanced, GTI Diagnostics). All positive and indeterminate samples were then tested using an IgG-specific PF4-H ELISA assay and a platelet serotonin-release assay. Participants were then followed up prospectively for thromboembolic events, cardiovascular events, or death.Results: During a median follow-up of 2.5 years there were 129 deaths. After controlling for important potential confounding variables, the relative risk of death was 2.92 (95% CI: 1.18-7.25; P= 0.02) in patients with IgG-specific PF4-H antibodies and 4.08 (95% CI: 1.26–13.2; P= 0.02) in patients with IgG-specific antibodies and an indeterminate serotonin-release assay. Conclusions: PF4-H antibody formation is associated with increased all-cause mortality in patients on chronic hemodialysis. Further investigation is needed to determine if anticoagulation with alternative agents would improve survival in this population.