Oral Anticoagulation in Patients With Liver Disease.
Qamar Arman,Vaduganathan Muthiah,Greenberger Norton J,Giugliano Robert P
Journal of the American College of Cardiology
Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population.
Glycoprotein IIb/IIIa antagonists.
Hook Karen M,Bennett Joel S
Handbook of experimental pharmacology
Mortality from ischemic cardiac disease in adults has been dramatically reduced by the development of novel therapies for inhibiting platelet function. Circulating platelets are maintained in a resting state and are activated at sites of vascular injury by exquisitely controlled mechanisms, thereby maintaining vascular integrity without causing intravascular thrombosis. As it became clear that platelets play a central role in arterial thrombosis, the processes of platelet activation, adhesion, and aggregation became logical targets for the development of antithrombotic agents.
Glutathione peroxidase-3 deficiency promotes platelet-dependent thrombosis in vivo.
Jin Richard C,Mahoney Christopher E,Coleman Anderson Laura,Ottaviano Filomena,Croce Kevin,Leopold Jane A,Zhang Ying-Yi,Tang Shiow-Shih,Handy Diane E,Loscalzo Joseph
BACKGROUND:Glutathione peroxidase-3 (GPx-3) is a selenocysteine-containing plasma protein that scavenges reactive oxygen species in the extracellular compartment. A deficiency of this enzyme has been associated with platelet-dependent thrombosis, and a promoter haplotype with reduced function has been associated with stroke risk. METHODS AND RESULTS:We recently developed a genetic mouse model to assess platelet function and thrombosis in the setting of GPx-3 deficiency. The GPx-3((-/-)) mice showed an attenuated bleeding time and an enhanced aggregation response to the agonist ADP compared with wild-type mice. GPx-3((-/-)) mice displayed increased plasma levels of soluble P-selectin and decreased plasma cyclic cGMP compared with wild-type mice. ADP infusion-induced platelet aggregation in the pulmonary vasculature produced a more robust platelet activation response in the GPx-3((-/-)) than wild-type mice; histological sections from the pulmonary vasculature of GPx-3((-/-)) compared with wild-type mice showed increased platelet-rich thrombi and a higher percentage of occluded vessels. Cremaster muscle preparations revealed endothelial dysfunction in the GPx-3((-/-)) compared with wild-type mice. With a no-flow ischemia-reperfusion stroke model, GPx-3((-/-)) mice had significantly larger cerebral infarctions compared with wild-type mice and platelet-dependent strokes. To assess the neuroprotective role of antioxidants in this model, we found that manganese(III) meso-tetrakis(4-benzoic acid)porphyrin treatment reduced stroke size in GPx-3((-/-)) mice compared with vehicle-treated controls. CONCLUSIONS:These findings demonstrate that GPx-3 deficiency results in a prothrombotic state and vascular dysfunction that promotes platelet-dependent arterial thrombosis. These data illustrate the importance of this plasma antioxidant enzyme in regulating platelet activity, endothelial function, platelet-dependent thrombosis, and vascular thrombotic propensity.
Portal vein thrombosis: yes or no on anticoagulation therapy.
Turon Fanny,Hernández-Gea Virginia,García-Pagán Juan Carlos
Current opinion in organ transplantation
PURPOSE OF REVIEW:To describe portal vein thrombosis (PVT) in the setting of cirrhosis especially in relation to its potential impact on liver transplantation. In addition, the safety and efficacy of anticoagulation is reviewed. RECENT FINDINGS:PVT in cirrhosis occurs in up to 26% of patients awaiting liver transplantation. Different studies have suggested that PVT impacts negatively post-liver transplantation survival, particularly in first year post-liver transplantation and when PVT is complete involving the porto-mesenteric confluence and not allowing physiological anastomosis. Anticoagulation is effective in preventing PVT progression and may achieve partial or complete PVT recanalization. Its use in patients with cirrhosis seems not to be associated with increased bleeding risk. SUMMARY:The goal of anticoagulation is to prevent thrombus extension to the superior mesenteric vein and/or favor recanalization if previously affected, allowing physiological anastomosis during liver transplantation and therefore improving outcome. Low-molecular-weight heparin and vitamin K antagonist have a similar safety profile without specific data in favor of any of them. Treatment with direct anticoagulants cannot be recommended yet because of limited experience in cirrhosis. Transjugular intrahepatic portosystemic shunt could be an alternative particularly if thrombosis progresses despite satisfactory anticoagulation and/or when PVT is associated with severe portal hypertension complications. However, careful consideration of potential risks and benefits of anticoagulation is recommended until further studies are conducted.