A possible role of thrombin-activatable fibrinolysis inhibitor in disturbances of fibrinolytic system in renal transplant recipients

Background. Cardiovascular disease (CVD) is a major cause of death in renal transplant recipients (RTR). Suppression of fibrinolysis plays a role in t he progression of atherosclerosis. Accelerated progression of atheroscleros is and fibrinolytic system suppression has been observed in RTR. Despite ma ny years of intensive research, the reason for impaired fibrinolysis in thi s patient population is not fully understood. Thrombin-activatable fibrinol ysis inhibitor (TAFI) is a recently discovered glycoprotein combining coagu lation and fibrinolysis. This study was conducted to evaluate concentration s of TAFI, markers of thrombin generation, endothelial injury, and some sta ndard laboratory parameters in RTR receiving triple immunosuppressive drug regimen. Methods. The study was performed in 29 stable, nondiabetic kidney transplan t recipients treated with cyclosporin A, azathioprine, and prednisone and i n 18 age- and sex-matched healthy volunteers. Soluble thrombomodulin (sTM), prothrombin fragments F1+2 (F1+2), thrombin-antithrombin complexes (TAT), plasmin-antiplasmin complexes (PAP), and TAFI were measured with commercial ly available kits. Results. The RTR group had significantly higher plasma levels of TAT, F1 2, sTM and TAFI than the healthy volunteers. There were no differences in P AP concentrations between the two groups Plasma sTM correlated inversely wi th creatinine clearance, body mass index, haemoglobin, and albumin. Plasma TAT level was positively associated with total cholesterol. TAFI antigen in fluenced negatively PAP antigen concentration. Conclusions. On the basis of our research, we concluded that elevated circu lating TAF1 antigen might be a new link in the pathogenesis of impaired fib rinolysis in RTR, and thus atherosclerosis progression. In the patient grou p there is also evidence of endothelial injury, followed by secondary activ ation of the coagulation cascade. Hypercholesterolaemia in RTR is associate d with enhanced thrombin activity.