Circulating platelet-derived microparticles with procoagulant activity may be a potential cause of thrombosis in uremic patients

Abstract

Clinical experience indicates that bleeding and thrombotic tendencies co-exist in uremic patients. Numerous studies have shown that platelet functional defects contribute to the bleeding tendency in uremic patients. In contrast, there are no solid studies clarifying the pathogenesis of the prothrombotic state in uremic patients. Platelet-derived microparticles (PMPs), which are small vesicles with procoagulant activity released from activated platelets, are thought to be involved in clinical thrombogenesis. This study addressed the question of why uremic patients are thrombophilic even though they have a bleeding tendency, focusing on the clinical significance of PMPs. The subjects were pre-dialyzed patients, patients under hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) therapy, and age-matched healthy controls. Analyses of PMPs were performed using a flow cytometer. Annexin V was used to probe procoagulant activity of PMPs. The impacts of the HD procedure, arteriovenous (AV) fistula, and recombinant human erythropoietin (rHuEPO) treatment on the release of PMPs were additionally assessed. Major results are: (1) PMP counts were significantly greater in each uremic group than in controls. The PMP counts were not different among three types of uremic groups; (2) PMP counts were significantly higher in uremic patients with thrombotic events than in those without thrombotic events; and (3) the HD procedure and existence of AV fistula did not affect PMP counts, but rHuEPO treatment possibly enhanced the PMP release in these patients. Elevated PMP counts may trigger thrombosis in uremic patients. The primary cause of PMP elevation in uremia was not clarified in this study.