Low plasma activated protein C-protein C inhibitor complex concentration is associated with vascular access failure in hemodialysis patients

Background: Vascular access failure is a common cause of morbidity in patients with end-stage renal failure on hemodialysis (HD). Activation of the coagulation system and formation of a thrombus play important roles in recurrent arteriovenous fistula/graft (AVFG) failure. Thrombin in complex with thrombomodulin (TM) activates the anticoagulant protein C and creates activated protein C (APC), which is subsequently inactivated by the protein C inhibitor (PCI). The plasma concentration of the complex between APC and PCI (P-APC-PCI complex) is increased in hypercoagulable states and is therefore a sensitive indicator of the degree of activation of blood coagulation. Methods: Thirty-five HD patients dialyzed through a functioning AVFG were studied. The period of patency of AVFGs was recorded. Blood was drawn before and after the HD session for the analysis of the APC-PCI complex, soluble TM concentration and activity, von Willebrand factor antigen and homocysteine. Results: Patients with frequent AVFG failures (n = 8) had a significantly lower level of P-APC-PCI complex (median 0.09 μg/l) than those with less frequent AVFG failures (median 0.18 μg/l; n = 27; p = 0.04). No other significant differences were found between the groups. Conclusion: Thus, a low level of P-APC-PCI complex may be associated with an increased risk of AVFG failure in HD patients. Further prospective studies are needed to confirm these results and to evaluate the possibility of prophylactic measures.