fondaparinux and Liver-Cirrhosis

Portal vein thrombosis (PVT) is a rare but serious complication in the decompensated stage of cirrhosis, and recurrent upper gastrointestinal bleeding and refractory ascites can occur in such patients. In decompensated cirrhotic patients, the application of conventional anticoagulant therapy is limited due to severe coagulation disorders, thrombocytopenia, and history of gastrointestinal bleeding.In this study, we sought to investigate the effect of fondaparinux on acute PVT in decompensated cirrhotic patients.Patients were treated with fondaparinux (2.5 mg, q 24 h, subcutaneously) in the region of the umbilicus for conventional liver protection, after a clear diagnosis was made and contraindications such as active bleeding were ruled out. Other anticoagulants and circulation-improving drugs were not administered. Platelet count, prothrombin time, international normalized ratio, D dimer (DD), and liver function were measured. Furthermore, portal vein color Doppler ultrasound was performed every 7 days while patients were treated with fondaparinux and after portal vein recanalization.The portal vein was recanalized in all patients after treatment (P = .018). The decline in DD had a predictive value for portal vein recanalization (P = .018). No side effects such as bleeding or thrombocytopenia occurred in any of the patients (P > .05).Selective factor Xa inhibitor fondaparinux is effective and safe for acute PVT in decompensated cirrhotic patients.

Topics: Adult; Aged; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Fondaparinux; Humans; International Normalized Ratio; Liver Cirrhosis; Male; Middle Aged; Platelet Count; Polysaccharides; Portal Vein; Predictive Value of Tests; Prothrombin Time; Treatment Outcome; Ultrasonography, Doppler; Vascular Surgical Procedures; Venous Thrombosis

Hospital-associated venous thromboembolism (HA-VTE) is a major cause of morbidity and mortality and is internationally recognized as a significant patient safety issue. While cirrhosis was traditionally considered to predispose to bleeding, these patients are also at an increased risk of VTE, with an associated increase in mortality. Hospitalization rates of patients with cirrhosis are increasing, and decisions regarding thromboprophylaxis are complex due to the uncertain balance between thrombosis and bleeding risk. This is further accentuated by derangements of hemostasis in patients with cirrhosis that are often considered contraindications to pharmacological thromboprophylaxis. Due to the strict inclusion and exclusion criteria of seminal studies of VTE risk assessment and thromboprophylaxis, there is limited data to guide decision making in this patient group. This guidance document reviews the incidence and risk factors for HA-VTE in patients with cirrhosis, outlines evidence to inform the use of thromboprophylaxis, and provides pragmatic recommendations on VTE prevention for hospitalized patients with cirrhosis. In brief, in hospitalized patients with cirrhosis: We suggest inclusion of portal vein thrombosis as a distinct clinically important endpoint for future studies. We recommend against the use of thrombocytopenia and/or prolongation of prothrombin time/international normalized ratio as absolute contraindications to anticoagulant thromboprophylaxis. We suggest anticoagulant thromboprophylaxis in line with local protocols and suggest low molecular weight heparin (LMWH) or fondaparinux over unfractionated heparin (UFH). In renal impairment, we suggest LMWH over UFH. For critically ill patients, we suggest case-by-case consideration of thromboprophylaxis. We recommend research to refine VTE risk stratification, and to establish the optimal dosing and duration of thromboprophylaxis.

Topics: Anticoagulants; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Thrombosis; Venous Thromboembolism

Portal vein thrombosis is the most common thrombotic complication in cirrhosis. About 60% of anticoagulated patients can achieve recanalization. Despite fondaparinux (FPX) theoretical advantages, data are lacking about safety and efficacy for treatment of portal vein thrombosis in cirrhosis.. Cirrhotic patients with portal vein thrombosis treated with FPX or low-molecular-weight heparin (LMWH) were retrospectively included. The extension of thrombosis at baseline and its evolution during anticoagulant treatment were evaluated. Patients were treated with LMWH or FPX at therapeutic dosage and reduction was considered in selected cases.. There were 124 patients included. Main portal vein branch, splenic, and superior mesenteric veins were involved in 84%, 13%, and 36% of cases, respectively. Forty-one patients (33%) were treated with FPX and 83 (67%) with LMWH. The probability of resolution of thrombosis at 36 months was significantly higher in patients treated with FPX than in those treated with LMWH (77% vs 51%; P = .001), particularly when prescribed at reduced dose. With multivariate analysis, the treatment with FPX (hazard ratio 2.38; P = .002) and use of a full dose (hazard ratio 1.78; P = .035) were independent predictors of portal vein full recanalization. Bleeding rate was higher in patients treated with FPX than in those treated with LMWH (27% vs 13%; P = .06).. FPX appears to be more effective than LMWH in the treatment of portal vein thrombosis when used at reduced dose, also in complete thrombosis. FPX should be considered among possible treatments for portal vein thrombosis in cirrhosis.

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Retrospective Studies; Venous Thrombosis

Topics: Acute Kidney Injury; Betacoronavirus; Coronavirus Infections; COVID-19; Disease Progression; Erythrocyte Transfusion; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Fondaparinux; Hematuria; Hepatorenal Syndrome; Humans; Liver Cirrhosis; Male; Melena; Mesenteric Ischemia; Middle Aged; Pandemics; Platelet Transfusion; Pneumonia, Viral; Portal Vein; Purpura; SARS-CoV-2; Severity of Illness Index; Thrombotic Microangiopathies

Portal vein thrombosis (PVT) is a frequent complication of cirrhosis. Benefit, safety, and duration of anticoagulant treatment in this setting are controversial issues. The aim of this study was to analyze the course of PVT in a large cohort of cirrhotic patients undergoing or not anticoagulation therapy.. The data of 182 patients who presented between January 2008 and March 2016 with cirrhosis and PVT with at least 3 months of follow-up after the first PVT detection were analyzed. Eighty-one patients received anticoagulants and 101 were untreated per physician discretion.. The extension of the thrombosis decreased by >50% in 46 (56.8%, with complete recanalization in 31/46) patients under anticoagulation and in 26 (25.7%) untreated patients. Of the 46 patients who underwent recanalization, 17 (36%) suffered recurrent thrombosis after stopping anticoagulation therapy. Kaplan-Meier analysis showed a higher survival rate in the treated group (p = 0.010). At multivariate analysis, anticoagulation was an independent factor associated with longer survival (HR:0.30, CI:0.10-0.91, p = 0.014). The Child-Turcotte-Pugh classes B/C negatively influenced survival (hazard ratio, (HR):3.09, confidence interval (CI):1.14-8.36, p = 0.027 for Child-Turcotte-Pugh B and HR:9.27, CI:2.67-32.23, p < 0.001 for Child-Turcotte-Pugh C). Bleeding complications occurred in 22 (21.8%) untreated and 16 (19.7%) treated patients, but in only four cases was it judged to be related to the anticoagulant treatment. No death was reported as a consequence of the bleeding events.. Anticoagulant treatment is a safe and effective treatment leading to partial or complete recanalization of the portal venous system in 56.8% of cases, improving the survival of patients with cirrhosis and PVT. Discontinuation of the therapy is associated with a high rate of PVT recurrence.

Topics: Aged; Anticoagulants; Esophageal and Gastric Varices; Female; Fondaparinux; Gastrointestinal Hemorrhage; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Venous Thrombosis

Treatment 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.. We evaluated the in vitro effect of clinically approved anticoagulant drugs in plasma from patients with cirrhosis.. Thirty 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.. Addition 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.. The 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.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation Tests; Dabigatran; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Male; Middle Aged; Morpholines; Polysaccharides; Rivaroxaban; Thiophenes; Thrombin

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.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Blood Coagulation; Blood Coagulation Tests; Dabigatran; Diagnostic Tests, Routine; Drug Monitoring; Factor Xa Inhibitors; False Negative Reactions; Female; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Male; Middle Aged; Morpholines; Polysaccharides; Prothrombin; Rivaroxaban; Sensitivity and Specificity; Thiophenes; Thrombophilia