Protein C and protein S deficiencies may be related to survival among hemodialysis patients

Abstract

Background Thrombophilia due to protein C (PC) and protein S (PS) deficiencies is highly prevalent among patients with stage 5 chronic kidney disease and is reported to arise due to extracorporeal circulation during hemodialysis (HD). This study aimed to evaluate the relationship between HD treatment and thrombophilia. Methods A total of 114 Japanese patients on maintenance HD (62 men, 52 women) were followed during 2008–2011. Their survival rates were compared against the duration of HD. Prior to each HD, coagulation/fibrinolysis parameters and PC and PS activities were measured using standard techniques. The patients were divided into two groups: Group 1, with PC and/or PS deficiencies ( n = 32), and Group 2, without PC and PS deficiencies ( n = 82). The influence of such deficiencies and duration of dialysis on survival was examined. Time-to-event analysis was applied using Kaplan-Meier estimates, and the log-rank test was proposed to test the equivalence of relative survival data. Hazard ratios and 95% confidence intervals (CI) were calculated. Results Of the 114 patients, 37 died (Group 1, 22; Group 2, 15). The hazard ratio (95% CI) was higher ( p = 0.004) in Group 1 than Group 2. Gene analyses of PC and PS were performed in 14 patients from Group 1. No mutations in either protein were observed. We analyzed the causes of death in both groups; however, the estimated thrombophilia-related incidence of death could not be determined due to small sample size of HD patients. Conclusions Our results suggest that PC and PS deficiencies may be related to survival in HD patients. However, this finding warrants additional research.

Platelet Abnormalities in CKD and Their Implications for Antiplatelet Therapy

“…Activation of the coagulation system on vascular injury results in consolidation of the platelet plug by fibrin formation. Patients with CKD who are conservatively treated and patients on hemodialysis present with hypercoagulability characterized by elevated levels of tissue factor, fibrinogen, D-dimer, Factor VIII, tissue plasminogen activator, and thrombinantithrombin complexes (70)(71)(72)(73), and reduced levels of the anticoagulant proteins, protein C and S (74,75). Moreover, fibrin clots formed in plasma from patients on hemodialysis show a denser prothrombotic structure and reduced permeability, associated with a higher cardiovascular mortality risk (76)(77)(78).…”

Procoagulant FVIII and Anticoagulant Protein C in Renal Failure Patients on Hemodialysis

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