Association of heparin-dependent antibodies and adverse outcomes in hemodialysis patients: A population-based study

OBJECTIVE: To determine whether some adverse outcomes of hemodialysis could be explained by subclinical heparin-induced thrombocytopenia (HIT). PATIENTS AND METHODS: Platelet factor 4 (PF4)-heparin antibodies were measured by enzyme-linked immunosorbent assay in a population-based cohort of hemodialysis patients. Participants were then followed up prospectively for thromboembolic events, cardiovascular events, or death. RESULTS: Of the 59 hemodialysis patients residing in Olmsted County, Minnesota, 57 (97%) agreed to study participation. The mean ± SD age of the patients was 64±17 years (median hemodialysis duration, 23 months), and 27 (47%) were women. The enzyme-linked immunosorbent assay was positive for PF4-heparin antibodies in 2 patients (3.5%). The PF4-heparin antibody content varied over a 10-fold range and was not associated with the duration of hemodialysis (P=.99). During a median follow-up of 798 days, 16 thrombotic events, 37 cardiovascular events, and 23 deaths (including 13 cardiovascular deaths) occurred. After adjusting for the Framingham risk score, the all-cause mortality rate was significantly higher for patients with the highest tertile of PF4-heparin antibody content compared with patients in the lower tertiles (hazard ratio, 2.47; P=.03). Furthermore, 8 (73%) of deaths in this tertile were due to cardiovascular causes (hazard ratio, 4.14; P=.02). CONCLUSIONS: Despite repetitive heparin exposure, the prevalence of HIT in patients undergoing maintenance hemodialysis is no greater than that anticipated for other patient populations. However, to our knowledge, this is the first study to show an association between elevated PF4-heparin antibodies and increased mortality rates in hemodialysis patients.