Pro‐thrombotic changes in platelet, endothelial and coagulation function following haemodialysis

Abstract

Objective: Heparin is commonly given during haemodialysis (HD) to prevent clot formation, but it is unclear how effectively this reduces the pro-thrombotic state. We aimed to determine the effect of a session of HD on markers of platelet, endothelial and coagulation activation. Method: Blood samples were taken from the vascular access of 55 patients immediately before and after a HD session. Platelet function was assessed by: i) Ultegra rapid platelet function assay (RPFA), using the agonists thrombin receptor activating peptide (TRAP) and arachidonic acid (ASA); ii) flow cytometric measurement of P-selectin expression and fibrinogen binding +/− ADP stimulation; iii) measurement of soluble P-selectin; and iv) measurement of soluble CD40L. Coagulation factors (thrombin-antithrombin [TAT] and D-dimer) and endothelial vWF were assessed by ELISA. Results: A mean of 70,535iU (SEM 331) of heparin was given during dialysis and 30 patients (55%) were on antiplatelet agents. Post-HD there were significant increases in unstimulated P-selectin (median [IQR] 0·73 [0·43–1·19] to 1·03 [0·6–2·03], p = 0·037), stimulated P-selectin (24·1 [16·4–34·0] to 30·1 [17·7–42], p < 0·001), soluble P-selectin (46·0 [24·7–81·9] to 63·4 [35·9–99·3], p = 0·002) and sCD40L (0·527 [0·23–1·167] to 0·623 [0·224–2·012], p = 0·036). Stimulated fibrinogen binding was increased post-HD (35·1 [21·5–49·5] to 42 [29·7–55·2], p < 0·001), but unstimulated fibrinogen binding was unchanged. TRAP and ASA-stimulated aggregation were reduced post-HD (192 [159–253] to 179 [148–206], p < 0·001) and (610 [483–643] to 530 [465–613], p = 0·009), respectively. There were increases post-HD in TAT (4·9 [4·3–7·6] to 9·2 [6·7–14·5], p < 0·001), D-dimer (862·6 [506·7–1359·0] to 1030·8 [705·9–1603·6], p < 0·008) and vWF (1·65 [1·33–2·31] to 2·0 [1·6–2·6], p < 0·001). Conclusion: This study has shown that despite the use of heparin markers of coagulation, platelet and endothelial activation are increased following HD. More effective medical strategies to reduce the pro-thrombotic state of patients on HD should be investigated.