Summary There is increasing recognition that thrombotic complications may occur in patients with cirrhosis, and literature on antithrombotic treatment in these patients is rapidly emerging. Due to extensive haemostatic changes in patients with cirrhosis, careful monitoring of anticoagulant therapy may be required. Recent data suggest that plasma levels of low molecular weight heparin (LMWH) are substantially underestimated by the anti‐activated factor X (anti‐Xa) assay in patients with cirrhosis. We studied the in vitro recovery of antithrombin (AT)‐dependent and –independent anticoagulant drugs in plasma from 26 patients with cirrhosis and 30 healthy controls and found substantially reduced anti‐Xa levels when AT‐dependent anticoagulant drugs were added to the plasma of patients with cirrhosis. LMWH (0·2 U/ml) had the poorest recovery in plasma from patients with cirrhosis (0·13 ± 0·06 U/ml, compared to 0·23 ± 0·03 U/ml in controls, P < 0·0001), followed by unfractionated heparin and fondaparinux. In contrast, the recovery of rivaroxaban and dabigatran was identical between patients and controls. These data suggest that the anti‐Xa assay cannot be used to monitor AT‐dependent anticoagulant drugs in patients with cirrhosis, as it substantially underestimates drug levels. The direct factor Xa and IIa inhibitors, however, may be monitored through the respective anti‐Xa and anti‐IIa assays in patients with cirrhosis.

BackgroundTreatment and prevention of thrombotic complications is frequently required in patients with cirrhosis. However anticoagulant therapy is often withheld from these patients, because of the perceived bleeding diathesis. As a result of the limited clinical experience, the anticoagulant of choice for the various indications is still not known.ObjectivesWe evaluated the in vitro effect of clinically approved anticoagulant drugs in plasma from patients with cirrhosis.Patients/MethodsThirty patients with cirrhosis and thirty healthy controls were studied. Thrombin generation assays were performed before and after addition of unfractionated heparin, low molecular weight heparin, fondaparinux, dabigatran, and rivaroxaban, to estimate anticoagulant potencies of these drugs.ResultsAddition of dabigatran led to a much more pronounced reduction in endogenous thrombin potential in patients compared to controls (72.6% reduction in patients vs. 12.8% reduction in controls, P<0.0001). The enhanced effect of dabigatran was proportional to the severity of disease. In contrast, only a slightly increased anticoagulant response to heparin and low molecular weight heparin and even a reduced response to fondaparinux and rivaroxaban was observed in plasma from cirrhotic patients as compared to control plasma.ConclusionsThe anticoagulant potency of clinically approved drugs differs substantially between patients with cirrhosis and healthy individuals. Whereas dabigatran and, to a lesser extent, heparin and low molecular weight heparin are more potent in plasma from patients with cirrhosis, fondaparinux and rivaroxaban showed a decreased anticoagulant effect. These results may imply that in addition to dose adjustments based on altered pharmacokinetics, drug-specific dose adjustments based on altered anticoagulant potency may be required in patients with cirrhosis.

Traditionally, perioperative bleeding complications were a major concern during orthotopic liver transplantation, but a tremendous decline in transfusion requirements has been reported over the last decade. In recent years, there has been an increasing awareness towards perioperative thrombotic complications, including liver vessel thrombosis, and systemic venous and arterial thromboembolic events. Whereas a number of these thrombotic complications were previously categorized as surgical complications, increasing clinical and laboratory evidence suggest a role for the haemostatic system in thrombotic complications occurring during and after transplantation. High levels of the platelet adhesive protein von Willebrand factor with low levels of its regulator ADAMTS13, an increased potential to generate thrombin, and temporary hypofibrinolysis are all indicative of increased haemostatic potential after transplantation. Clinical evidence for a role of the haemostatic system in post-operative thromboses includes a higher thrombotic risk in patients with various acquired thrombotic risk factors. Although data on efficacy of anticoagulant therapy after liver transplantation are scarce, one study has shown a significant decrease in the risk for late hepatic artery thrombosis by antithrombotic therapy with aspirin. These findings suggest that antihaemostatic therapy in prevention or treatment of thromboembolic complications after liver transplantation may be relevant. Studies on efficacy and safety of these interventions are required as many of the thrombotic complications have a pronounced negative impact on graft and patient survival.