Introduction: Heparin-induced thrombocytopenia (HIT) is a syndrome in which anti-platelet factor 4/heparin antibodies (HITab) and thrombocytopenia develop after heparin exposure. While HIT is an established risk factor for arterial and venous thromboses, HITab, in the absence of thrombocytopenia, may also be a prothrombotic risk factor. As patients with chronic kidney disease on hemodialysis are chronically exposed to heparin, we hypothesized that the presence of HITab may contribute to the high rates of thrombotic disease and mortality in these patients.
Patients and methods: We analyzed data from the CHOICE study, a prospective cohort study of incident dialysis patients. Clinical data were available from medical record review. Arterial cardiovascular events and events of vascular access occlusion were validated by chart review and adjudication. Venous thromboembolic events were defined by ICD-9 codes. Thrombocytopenia was defined as a platelet count <150,000/mm3 or a >50% decline from a previous platelet count. Median duration of follow-up is 2.7 years. We measured HITab using a commercial ELISA assay in stored serum obtained 6 months after cohort enrollment of 740 participants (596 on hemodialysis, 144 on peritoneal dialysis). ELISA results were corrected for inter-plate variability. A positive HITab test associated with thrombocytopenia in the subsequent three months was considered compatible with HIT. We used techniques of logistic regression and of survival analysis with adjustment for potential confounders in our analyses.
Results: 10.3% of all patients were positive for HITab at six months. HITab positivity was not associated with thrombocytopenia. HITab did not predict subsequent outcomes including cardiovascular (hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.65–1.41), vascular access occlusive (HR 0.82, CI 0.40–1.71), or venous thromboembolic events (HR 1.39, CI 0.17–11.5) and did not predict mortality (HR 1.00, CI 0.66–1.53). 9 patients (1.2%) had results compatible with HIT (thrombocytopenia + HITab). 1 patient with HIT (0.13%) had venous thrombosis yielding a hazard ratio of 13.7 (CI 1.63–115.5) for HIT and thrombosis.
Conclusions: HITab seropositivity after six months of dialysis is frequent, but is not associated with thrombocytopenia. In end-stage renal disease patients treated by dialysis HITab seropositivity in the absence of thrombocytopenia is not an independent risk factor for cardiovascular morbidity or mortality. However, HIT may occur in this patient population and is associated with thrombosis.