Haemostatic effects of erythropoietin treatment with and without acetylsalicylic acid in individuals with chronic kidney disease: a prospective single-arm repeated-measures study

Background Erythropoiesis-stimulating agents (ESAs) are used to treat anemia in chronic kidney disease (CKD). ESAs have been associated with increased thrombotic risk, but the underlying mechanisms remain unclear. Given its antiplatelet effects and widespread use in cardiovascular prevention, we hypothesized that concomitant acetylsalicylic acid (ASA) attenuates ESA-induced prothrombotic alterations in hemostasis in patients with CKD. Methods We conducted a prospective single-arm, repeated-measures, interventional phase 4 study in 27 individuals with advanced CKD (hemodialysis, peritoneal dialysis, and non-dialysis). The study comprised four consecutive 4-week phases: ESA washout, ESA treatment, ESA plus ASA (75 mg daily), and post-treatment washout. At the end of each phase, we assessed platelet function, whole-blood coagulation, endothelial activation, coagulation activation, and fibrinolysis. Results ESA treatment induced a modest and reversible increase in platelet count, whereas markers of immature platelets (IPF and H-IPF) decreased. Soluble P-selectin increased slightly during ESA treatment, indicating mild platelet and/or endothelial activation. Platelet aggregation, thromboelastometry parameters, prothrombin fragment 1 + 2, fibrin D-dimer, soluble thrombomodulin, and fibrinolysis markers remained largely unchanged throughout ESA treatment and ASA had no effect on ESA-related changes. Conclusions In individuals with advanced CKD, short-term ESA treatment was associated with modest changes in platelet count and soluble P-selectin but did not result in measurable changes in platelet function, coagulation activity or fibrinolysis. ASA did not modify ESA-related effects and did not induce measurable haemostatic changes. These findings do not support a major systemic procoagulant effect of ESA, indicating that alternative mechanisms might contribute to the increased thrombotic risk observed in clinical trials.