fondaparinux and Chemical-and-Drug-Induced-Liver-Injury

Hepatotoxicity with low-molecular-weight heparin (LMWH) or fondaparinux is a relatively common adverse reaction. This study assessed the effects of LMWH and fondaparinux on liver function in patients with pulmonary embolism based on a retrospective cohort. As a result, a total of 463 patients with pulmonary embolism and treated with LMWH (enoxaparin sodium or nadroparin calcium) or fondaparinux sodium were included. Liver dysfunction was identified in 79 patients (17.1%), of whom 97.5% had grade 1 drug-induced liver injury (DILI) and 2.5% had grade 2 DILI. The results showed that liver dysfunction usually occurred in the first week after anticoagulant administration, and the liver tests of all patients with liver dysfunction gradually recovered or alleviated at discharge. The multivariable logistic regression analysis indicated that a longer treatment course and hepatitis B surface antigen-positive (HBsAg+) were risk factors for liver dysfunction (P < .05). Moreover, nadroparin calcium had the highest risk of liver dysfunction, approximately 2.2 times (95% confidence interval [CI], 1.1740-4.224; P = .015) that of enoxaparin sodium. In conclusion, nearly one-fifth and 10% of patients prescribed with LMWH or fondaparinux, respectively, for pulmonary embolism had liver dysfunction, mainly with mild liver injury and characterized by self-limited elevated serum transaminase levels. Hence, during the 3 anticoagulant applications, we should pay more attention to the monitoring of liver function in the first week and transit to oral anticoagulants if possible, especially for patients who are HBsAg+ or suffering from other liver diseases.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Asian People; Chemical and Drug Induced Liver Injury; Drug Combinations; Enoxaparin; Factor Xa Inhibitors; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Hepatitis B Surface Antigens; Humans; Liver; Male; Middle Aged; Nadroparin; Pulmonary Embolism; Retrospective Studies; Risk Factors; Time Factors

Topics: Acute Disease; Anticoagulants; Axillary Vein; Chemical and Drug Induced Liver Injury; Child; Fondaparinux; Humans; Polysaccharides; Vascular Malformations

Therapy for venous thromboembolism (VTE) currently involves a minimum of 3 months of anticoagulation. After cessation of therapy, however, recurrent venous thrombosis occurs at rates of 6 to 9% per year. Clinical trials have demonstrated the benefits of extending anticoagulation beyond 3 months for the prevention of recurrent VTE events. Despite this, many eligible patients do not receive the required thromboprophylaxis and the incidence of recurrent VTE remains too high for a preventable condition. A reason for failure to use prophylaxis is the fear of bleeding complications with current oral anticoagulants such as warfarin. Warfarin has an unpredictable pharmacokinetic profile and a variable dose-response relationship that requires frequent coagulation monitoring and dose adjustments to maintain a target intensity that is both safe and effective. Alternative strategies for long-term prophylaxis, which may potentially provide more consistent anticoagulant responses and reduce coagulation monitoring requirements, include the use of low-molecular-weight heparin (LMWH), treatment with warfarin at a lower intensity, and the introduction of novel anticoagulants. The long-term use of LMWH has been found to be a particularly favorable treatment option for cancer patients in whom it is difficult to control the intensity of anticoagulation. In clinical trials, LMWH significantly reduced the risk of recurrent VTE without increasing bleeding risk. The parenteral administration of the LMWHs, however, is a drawback for long-term use in the outpatient setting. A clinical trial assessing the efficacy and safety of long-term low-intensity warfarin treatment found this therapy to be better than placebo, but another study showed that conventional intensity warfarin was significantly more efficacious than low-intensity warfarin. New therapies in development that may offer improved safety-efficacy profiles are the synthetic pentasaccharides fondaparinux and idraparinux and the oral direct thrombin inhibitor ximelagatran. Parenterally administered fondaparinux has been shown to be as effective as LMWH for the acute treatment (5 to 7 days) of symptomatic deep vein thrombosis. Idraparinux, with once-weekly parenteral dosing, is currently being assessed in phase III clinical trials for the long-term secondary prevention of VTE. Ximelagatran is the first oral agent in the new class direct thrombin inhibitors. With a fast onset of action and oral administration, ximelagatran is a

Topics: Anticoagulants; Azetidines; Benzylamines; Chemical and Drug Induced Liver Injury; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Myocardial Ischemia; Oligosaccharides; Polysaccharides; Recurrence; Thrombin; Time Factors; Venous Thrombosis; Warfarin