Activated platelets and coagulation in patients on haemodialysis

Abstract

Objective: Patients on haemodialysis (HD) have an increased risk of cardiac events. Controversy exists as to whether these patients have a pro-thrombotic state. We aimed to determine markers of platelet activation and coagulation in patients on HD compared with healthy volunteers. Method: Platelet function was assessed in 78 patients pre-HD and 78 volunteers by: i) Ultegra rapid platelet function assay using the agonists thrombin receptor activating peptide (TRAP) and arachidonic acid (ASA); ii) flow cytometry of P-selectin expression and fibrinogen binding with/without ADP stimulation; and iii) measuring plasma soluble P-selectin. Coagulation and fibrinolysis were assessed by ELISA determination of thrombin-antithrombin (TAT) and D- dimer, respectively. Results: ASA-stimulated platelet aggregation was significantly reduced in HD patients, of whom 50 (64%) were on aspirin therapy (median [IQR] 555 [355–671] versus 649 [385–675], p < 0·001). TRAP-mediated aggregation was similar in both groups. Unstimulated fibrinogen binding was significantly increased in patients (2·02 [1·48–2·62] versus 1·46 [1·15–1·94], p < 0·001) but stimulated fibrinogen was decreased (40·75 [26·7–50·3] versus 50·05 [40·6–59·9], p < 0·001). Unstimulated P-selectin was significantly decreased in patients (0·82 [0·52–1·46] versus 1·62 [0·86–2·34], p < 0·001), yet soluble P-selectin was significantly increased (43·26 [13·88–86·7] versus 24·67 [13·41–43·32], p = 0·039). Stimulated P-selectin was similar in both groups. Markers of coagulation were significantly increased in patients on HD: TAT 4·59 (2·67–6·04) versus 2·84 (1·81–3·82), p < 0·001 and D-dimer 876·5 (434·2–1338·5) versus 265·5 (175·0–401·51), p < 0·001. Conclusion: Patients on HD have a pro-thrombotic state with chronically activated platelets and elevated markers of coagulation. Drug therapy to counteract this pro-thrombotic state should be considered with the aim of preventing both cardiac events and vascular access thrombosis.