Significance of mild thrombocytopenia in maintenance hemodialysis patients; a retrospective cohort study.

Platelet activation in the hemodialysis (HD) circuit often causes thrombocytopenia. However, its clinical and pathophysiological significance has rarely been explored. Herein, we investigated the predictive value of thrombocytopenia for cardiovascular events (CVE) in maintenance HD patients and attempted to explore its mechanistic background considering recent knowledge of platelet dynamics. We conducted a retrospective cohort study on HD patients with the composite primary endpoint of predicting CVE, i.e., myocardial infarction, ischemic stroke, and cardiovascular death. Baseline clinical data were analyzed and explored. Multivariate Cox regression analysis showed that platelet decrease was independently associated with CVE. Thrombocytopenia was correlated with the disuse of antiplatelet therapy (APT) and macrocytosis. These findings are possibly associated with platelet activation and senescent hematopoiesis. The prognostic significance of thrombocytopenia was more prominent in patients undergoing APT, implying the presence of APT-resistant platelets in such patients. To fully explain these results, we hypothesized that HD-activated platelets induce the biological aging of hematopoiesis, which is presumably extramedullary in the lung, where activated platelets could deliver massive amounts of inflammatory cytokines and reactive oxidative species. This results in the production of qualitatively altered and hyper-reactive platelets, a process that could form a vicious cycle that induces CVE-associated thrombocytopenia. Further investigations focusing on the dynamics of the biological aging of platelets in HD patients are warranted.