The Effect of Immunosuppression on Coagulation After Liver Transplantation

Abstract

Everolimus (EVR) is a mammalian target of rapamycin (mTOR) inhibitor commonly used for immunosuppression (IS) after liver transplantation (LT). However, there are concerns about whether mTOR inhibitors may move the hemostatic balance toward a higher likelihood of thrombosis. The present study aimed to investigate potential coagulation disorders after the administration of EVR. We evaluated 54 patients after conversion to an EVR‐based IS regimen (n = 26) and compared those patients with patients who were switched to extended‐release tacrolimus (TAC) but had never received EVR (n = 28). At baseline and again at 1 month and 6 months after conversion, we measured international normalized ratio, activated partial thromboplastin time, and anticoagulation and fibrinolysis factors, and we performed rotational thromboelastometry (ROTEM). Data were analyzed with a Mann‐Whitney U test, a repeated‐measure analysis of variance, and a Fisher’s exact test. Statistical significance was set at the level of P ≤ 0.05. Plasma levels of von Willebrand factor, fibrinogen, and factor VIII were significantly higher than baseline levels at 1 month and 6 months after conversion of IS to EVR (P < 0.001); plasma levels of protein C, protein S, and plasminogen also increased significantly (P < 0.001). ROTEM confirmed a significant increase in maximum clot firmness in EXTEM, INTEM, and FIBTEM assays (P < 0.001). In all assays, maximum lysis was significantly lower than baseline levels at 1 month and 6 months after conversion to EVR. Patients converted to IS with extended‐release TAC exhibited no significant changes in coagulation variables. Retrospective analysis showed a significantly higher incidence of thromboembolic complications among patients treated with EVR‐based IS than among those treated with extended‐release TAC (P < 0.01). In conclusion, the administration of EVR after LT seems to modify hemostasis to a procoagulant state. Thrombophilia screening before conversion may determine which patients will benefit from conversion to EVR‐based IS.

Exploring the Complex Role of Coagulation Factor VIII in Chronic Liver Disease

“… 114 , 115 Several studies have reported that during the intraoperative and early postoperative phase, the plasma FVIII level usually increases. 114 , 115 Patients with end-stage liver disease undergoing liver transplantation consistently have higher FVIII levels than patients who survived had end stage liver disease but did not undergo treatments such as liver transplantation, 116 consistent with the severity of their liver disease and criteria for transplantation based on the severity of end-stage liver disease. Studies have shown that FVIII levels also are increased in children undergoing liver transplantation.…”