M. P. Chapman2,4, E. E. Moore1,2, H. B. Moore1,2, D. Burneikis2, E. Gonzalez1,2, A. Slaughter1,2, A. P. Morton2, A. Banerjee2, C. C. Silliman2,3 1Denver Health Medical Center,Aurora, CO, USA 2University Of Colorado Denver,Aurora, CO, USA 3Children’s Hospital Colorado,Aurora, CO, USA 4Georgia Health Sciences University,Augusta, GA, USA
Introduction:
Patients in end-stage renal disease (ESRD) display various derangements of coagulation. Our previous work has demonstrated a a mixed pattern of hypo- and hypercoagulability in these patients, with a paradoxical prolongation of the enzymatic phase of clot formation followed by rapid clot growth and elevated final clot strength. We sought to clarify the detailed features of the hypercoagulable component of the coagulopathy of ESRD to develop targets for prophylactic therapy aimed at prevention of dialysis access graft thrombosis.
Methods:
Blood was collected from 16 consecutive ESRD patients at the time of dialysis access construction and compared to that of 53 healthy volunteers using multichannel thrombelastography (TEG). Rapid TEG and functional fibrinogen (platelet-inhibited) TEG were used to assess clot strength and the relative contributions of platelets and fibrinogen. tPA-challenged TEG was used to assess fibrinolysis susceptibility, using the clot lysis at 30 minutes (LY30) parameter of TEG, when the sample is challenged with exogenous tPA. Platelet function was assessed by aggregometry and TEG platelet mapping.
Results:
Overall clot strength, measured by Rapid TEG maximum amplitude (MA), was elevated at 71±6 mm in ESRD patients compared to 66±4 for healthy controls (p=0.0005, two-tailed Mann-Whitney test). Functional fibrinogen level (by platelet-inhibited TEG MA) was even more markedly elevated at 32 (IQR 29-37) mm in ESRD patients versus 20 (IQR 17-22) mm for controls (p<0.0001). ESRD patients also displayed increased resistance to fibrinolysis, with a tPA-challenged TEG LY30 of 29% (IQR 15-39%) compared to 56% (IQR 40-65%) for healthy controls (p=0.0004). Platelet function tests on ESRD patients were within normal limits.
Conclusion:
Hyperfibrinogenemia and impaired fibrinolysis are responsible for the hypercoagulability observed in ESRD and may contribute to graft/fistula thrombosis. As enzymatic clotting is already prolonged in ESRD and platelet function is generally normal, traditional agents such as heparin or aspirin are of limited prophylactic benefit in prevention of graft/fistula thrombosis. Therapeutic agents effecting fibrin clot strength and fibrinolysis (e.g factor XIIIa inhibitors, PAI-1 antagonists or low dose thrombolytics) may therefore be of greater utility for preservation of dialysis access.
