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- W2009411164 abstract "Potential conflict of interest: Nothing to report. To the Editor: There is increasing interest in treatment and prevention of cirrhotic portal vein thrombosis (PVT) with anticoagulant drugs.1 Two recent reports in Hepatology suggested efficacy and safety of new‐generation oral anticoagulant drugs (the direct factor Xa inhibitors, Rivaroxaban and Apixaban) in treatment of PVT in patients with compensated cirrhosis.2 These new drugs have practical advantages over traditional anticoagulants.4 We recently showed altered in vitro potency of different anticoagulant drugs in patients with cirrhosis, compared to patients with intact liver function.5 A theoretical risk for excessive anticoagulation when using these drugs in patients with cirrhosis and concomitant alterations in their hemostatic system exists. We previously demonstrated a decreased in vitro anticoagulant effect of Rivaroxaban in patients with cirrhosis. Using thrombomodulin‐modified thrombin generation testing, we examined the in vitro anticoagulant potency of Apixaban, which we compared to the anticoagulant potency of Rivaroxaban. This study protocol was approved by the medical ethical committee of the University Medical Center Groningen (Groningen, The Netherlands), and written informed consent was obtained from each subject before inclusion in the study. We added vehicle, 25 ng/mL of Apixaban, or 50 ng/mL of Rivaroxaban to plasma samples of 11 healthy individuals and 14 patients with cirrhosis (9 patients with Child B cirrhosis and 5 with Child C cirrhosis). We performed thrombin generation tests in the presence of thrombomodulin and calculated the percentual decrease in total thrombin generation by the two anticoagulant drugs, as described previously.5 Whereas a fixed dose of the drugs decreased total thrombin generation in healthy volunteers by 55 ± 6% (Rivaroxaban, mean ± standard deviation) and 51 ± 4% (Apixaban), the mean decrease in thrombin generation in patients was significantly lower (30 ± 9% for Rivaroxaban, P < 0.0001 [t test]; 32 ± 10% for Apixaban, P < 0.0001). In conclusion, the in vitro anticoagulant potency of Apixaban is substantially reduced in patients with moderate and advanced cirrhosis, similar to the reduced potency of Rivaroxaban, which we previously reported. These results suggest that anticoagulant treatment with these direct factor Xa inhibitors will likely not result in overanticoagulation, with a potentially increased bleeding risk, provided drug levels remain in the target range. Careful monitoring of drug levels, for example, by anti‐Xa testing,6 may be required." @default.
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- W2009411164 date "2015-03-09" @default.
- W2009411164 modified "2023-10-05" @default.
- W2009411164 title "Decreased in vitro anticoagulant potency of Rivaroxaban and Apixaban in plasma from patients with cirrhosis" @default.
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- W2009411164 doi "https://doi.org/10.1002/hep.27350" @default.
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