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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., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Background: In patients with liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) is considered a standardized treatment of refractory ascites or variceal bleeding. TIPS thrombosis (TT) and/or portal vein thrombosis (PVT) are possible complications during/after TIPS placement. Previous studies suggested increased clotting activity in portal circulation (PORC). This pilot study aimed to evaluate alterations and differences of coagulation function in PORC and in peripheral circulation (PERC) via rotational thromboelastometry during TIPS. Methods: Blood samples were collected from cirrhotic patients (n = 13; median Model of End Stage Liver Disease, MELD Score: 12; median age: 60 years) undergoing TIPS (10/13 TIPSs were elective procedures due to refractory ascites) as follows: median cubital vein (MCV; PERC)—confluence of the three hepatic veins to the inferior cava vein (HV/ICV; PORC)—portal vein (PV; PORC)—TIPS (PORC). This research utilized four variables of the extrinsic test EXTEM, i.e., clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and maximum lysis (ML). Results: EXTEM results [mean, M (range) ± standard deviation, SD (range)] showed no significant differences for CT [M (70–73) ± SD (9–13); p = 0.93] or CFT [M (137–155) ± SD (75–112); p = 0.97] or MCF [M (51–54) ± SD (9–10); p = 0.90] or ML [M (9–10) ± SD (4–5); p = 0.89] between the compartments, i.e., MCV vs. HV/ICV vs. PV vs. TIPS. Overall, we detected no differences in coagulation function between PERC and PORC. Conclusion: These results are in contrast to previous reports suggesting increased clotting activity in PORC vs. PERC in association with liver cirrhosis. Rotational thromboelastometry-based evaluation of coagulation function in PERC appears to reliably reflect coagulation function in PORC with respect to risk estimation for TT and/or PVT in cirrhotic patients undergoing TIPS. [ABSTRACT FROM AUTHOR]