Treatment response and bleeding events associated with anticoagulant therapy of portal vein thrombosis in cirrhotic patients: Systematic review and meta-analysis.
ABSTRACT: Background:Well-defined guidelines for the treatment of portal vein thrombosis (PVT) in patients with cirrhosis are lacking, given the paucity of robust data. Among the available treatment options the best choice is unknown. Methods:We conducted a comprehensive search of multiple electronic databases and conference proceedings (through December 2019) to identify studies that reported on the use of anticoagulants in the treatment of PVT in patients with cirrhosis. Our goals were to evaluate the pooled odds ratio (OR) and pooled rate of treatment responders and bleeding events. Results:A total of 17 studies were included: 648 patients were treated with anticoagulation and 96 were controls. Pooled OR for treatment responders was 5.1 (95% confidence interval [CI] 2.5-10.2, P = 0.001) and pooled OR for bleeding was 0.4 (95%CI 0.1-1.5, P = 0.2) for anticoagulation treatment versus control. Pooled rate of treatment responders with anticoagulation was 66.7% (95%CI 58.3-74.1) compared to 26% (95%CI 14.2-42.7) for the control group. Pooled rate of bleeding seemed comparable (7.8%, 95%CI 4.5-13.3, and 15.4%, 95%CI 4.3-42.7). On subgroup analysis, pooled rates of treatment responders and bleeding events seemed similar between low molecular weight heparin, vitamin K antagonists, and direct oral anticoagulants. Conclusions:Our study demonstrated that anticoagulation is effective and safe in the treatment of PVT in patients with cirrhosis. Owing to the comparable outcomes, direct oral anticoagulants may be considered as first-line treatment, depending on patient preferences.
Project description:Nontumoral portal vein thrombosis (PVT) is an increasingly recognized complication in patients with cirrhosis. Substantial evidence shows that portal flow stasis, complex thrombophilic disorders, and exogenous factors leading to endothelial dysfunction have emerged as key factors in the pathogenesis of PVT. The contribution of PVT to hepatic decompensation and mortality in cirrhosis is debatable; however, the presence of an advanced PVT increases operative complexity and decreases survival after transplantation. The therapeutic decision for PVT is often determined by the duration and extent of thrombosis, the presence of symptoms, and liver transplant eligibility. Evidence from several cohorts has demonstrated that anticoagulation treatment with vitamin K antagonist or low molecular weight heparin can achieve recanalization of the portal vein, which is associated with a reduction in portal hypertension-related events and improved survival in cirrhotic patients with PVT. Consequently, interest in direct oral anticoagulants for PVT is increasing, but clinical data in cirrhosis are limited. Although the most feared consequence of anticoagulation is bleeding, most studies indicate that anticoagulation therapy for PVT in cirrhosis appears relatively safe. Interestingly, the data showed that transjugular intrahepatic portosystemic shunt represents an effective adjunctive therapy for PVT in cirrhotic patients with symptomatic portal hypertension if anticoagulation is ineffective. Insufficient evidence regarding the optimal timing, modality, and duration of therapy makes nontumoral PVT a challenging consequence of cirrhosis. In this review, we summarize the current literature and provide a potential algorithm for the management of PVT in patients with cirrhosis.
Project description:Portal vein thromboses (PVTs) are associated with hepatic decompensation, worse survival, and worse liver transplant outcomes. We evaluated the impact of anticoagulation (AC) and transjugular intrahepatic portosystemic shunting (TIPS) on recanalization and mortality in patients with cirrhosis and PVT. Systematic search of electronic databases was performed. Clinical trials and observational studies that evaluated primary outcomes of recanalization and survival in patients with cirrhosis having PVT treated with AC or TIPS were included. Risk of bias was assessed. Summary odds ratios (ORs) for pooled data from the included studies were generated using a random effects model. A total of 505 studies were screened for inclusion. After review, 7 studies were ultimately included. Data from 327 patients in total were evaluated. Overall, treatment with either AC or TIPS resulted in partial or complete recanalization (OR: 4.56 [95% confidence interval, CI: 2.46-8.47]) but did not significantly impact mortality (OR: 0.57 [95% CI: 0.21-1.57]). The summary OR of AC for recanalization was 6.00 (95% CI: 2.38-15.07). The summary OR of TIPS for recanalization was 3.80 (95% CI: 1.47-9.83). The summary OR of mortality in patients treated with AC for PVT was 0.28 (95% CI: 0.08-0.95). The mortality summary OR was 1.10 (95% CI 0.23-5.16) in patients who underwent TIPS. There was insufficient data to assess complications such as hepatic encephalopathy or bleeding. Both AC and TIPS have a significant effect on recanalization. Anticoagulation appears to have a protective effect on mortality that is not seen with TIPS. More studies with control groups are need.
Project description:The presence of occlusive portal vein thrombosis (PVT) greatly changes the natural history of liver cirrhosis, because it not only significantly increases the incidence of variceal rebleeding but also negatively influences the survival. However, due to the absence of strong evidence, no standard treatment algorithm for the secondary prophylaxis of variceal bleeding in cirrhotic patients with non-tumoral PVT has been established. Previous randomized controlled trials have demonstrated that transjugular intrahepatic portosystemic shunt (TIPS) can significantly decrease the incidence of variceal rebleeding in cirrhotic patients without PVT, compared with conservative therapy (i.e., endoscopic plus pharmacological therapy). Further, several large cohort studies have confirmed that TIPS can effectively prevent variceal rebleeding in cirrhotic patients with non-tumoral PVT. On the other hand, TIPS can facilitate recanalizing the thrombosed portal vein by endovascular manipulations, even in the presence of cavernous transformation of the portal vein (CTPV). More importantly, successful TIPS insertions can maintain the persistent portal vein patency, and avoid thrombus extension into the portal venous system. By comparison, anticoagulation therapy can achieve portal vein recanalization only in patients with partial PVT, but not in those with occlusive PVT or CTPV, and the use of anticoagulants may aggravate the risk of variceal bleeding in cirrhotic patients with a history of variceal bleeding. Collectively, we hypothesize that TIPS may be superior to conservative therapy for the prevention of variceal rebleeding in cirrhotic patients with non-tumoral PVT. Randomized controlled trials should be conducted to evaluate the survival benefit of TIPS in these patients.
Project description:INTRODUCTION:Anticoagulation therapy in portal vein thrombosis (PVT) in patients with cirrhosis is still a matter of debate. Therefore, the aim of this work was to evaluate the efficacy and safety of nadroparin calcium-warfarin sequential (NWS) anticoagulation therapy in cirrhotic patients and to find an optimal anticoagulation strategy. METHODS:Consecutive cirrhotic patients with PVT who have not received anticoagulation therapy were randomly divided into the NWS therapy group (1-month nadroparin calcium by subcutaneous injection followed by 5-month warfarin by oral administration) and control group (no anticoagulation therapy). Overall recanalization rate of PVT and risks of bleeding were evaluated at the sixth month. RESULTS:Among 64 patients, complete or partial recanalization of PVT was observed in 20/32 NSW therapy group patients vs 11/32 control group patients (62.5% vs 34.4%, P = 0.024), with no statistically significant difference in bleeding rate. Child-Pugh score (P = 0.023), D-dimer < 2.00 ?g/mL (P = 0.020), and NWS anticoagulation therapy (P = 0.004) were predictors associated with the recanalization. NWS anticoagulation therapy (P = 0.008) was an independent predicting factor of recanalization. In the NWS therapy group, the Child-Pugh score (P = 0.007) and albumin level (P = 0.004) were improved in the sixth month. DISCUSSION:NWS anticoagulation therapy was effective and safe in PVT patients with cirrhosis and could increase the level of albumin. NWS therapy is safe and easily accepted.
Project description:<b>Background and Objective:</b> Minor dental surgery is invasive and hemorrhagic. Thus, in patients treated with anticoagulants, the bleeding risk related to these invasive procedures is concerning. The aim of this meta-analysis is to evaluate this risk by comparing the post-operative bleeding rates of oral anticoagulation treatment (OAT) patients (without interrupted or altered anticoagulant intake) with non-OAT patients. <b>Methods:</b> PubMed, Embase and the Cochrane Library were searched for eligible studies that compared the post-operative (following minor dental surgery) bleeding rates of OAT patients without interrupted or altered therapy with those of non-OAT patients. Relative risk (RR) and 95% confidence interval (CI) were calculated. Subgroup analyses were used to identify the association between the bleeding rate and different dental surgeries or anticoagulants. <b>Results:</b> Thirty two full text articles were assessed for eligibility and 20 studies were excluded according to the selection criteria. Finally, 12 studies and a total of 2102 OAT patients and 2271 non-OAT patients were included. A pooled analysis indicated that the post-operative bleeding risk in OAT patients is higher than that of non-OAT patients (RR: 2.794, 95% CI: 1.722-4.532, <i>P</i> = 0.000). The pooled RRs in the dental implant surgery and dental extraction subgroups were 2.136 (95% CI: 0.825-5.531, <i>P</i> = 0.118) and 2.003 (95% CI: 0.987-4.063, <i>P</i> = 0.054), respectively. As for the different oral anticoagulants, the pooled RR in the subgroup of new oral anticoagulants (NOACs) was 1.603 (95% CI: 0.430-5.980, <i>P</i> = 0.482), while the pooled RR in the vitamin K antagonists subgroup was 3.067 (95% CI: 1.838-5.118, <i>P</i> = 0.000). <b>Conclusion:</b> Under current evidence, OAT patients were under a higher post-operative bleeding risk than the non-OAT patients following minor dental surgery. For the dental implant surgeries and dental extractions, our study failed to demonstrate a higher risk of bleeding in the OAT patients compared with the non-OAT patients. Besides, The NOACs might be safer than the vitamin K antagonists in dental implant surgery. However, more well-designed studies are required for future research.
Project description:<h4>Background</h4>Left ventricular thrombus (LVT) is not uncommon and pose a risk of systemic embolism, which can be mitigated by adequate anticoagulation. Direct oral anticoagulants (DOACs) are increasingly being used as alternatives to warfarin for anticoagulation, but their efficacy and safety profile has been debated. We aim to compare the therapeutic efficacy and safety of DOACs versus warfarin for the treatment of LVT.<h4>Methodology</h4>We systematically searched PubMed/Medline, Google Scholar, Cochrane library, and LILCAS databases from inception to 14th August 2020 to identify relevant studies comparing warfarin and DOACs for LVT treatment and used the pooled data extracted from retrieved studies to perform a meta-analysis.<h4>Results</h4>We report pooled data on 1955 patients from 8 studies, with a mean age of 61?years and 59.7?years in warfarin and DOACs group, respectively. The pooled odds ratio for thrombus resolution was 1.11 (95% CI 0.51-2.39) on comparing warfarin to DOAC, but it did not reach a statistical significance (p?=?0.76). The pooled risk ratio (RR) of stroke or systemic embolization and bleeding in patients treated with warfarin vs DOACs was 1.04 (95% CI 0.64-1.68; p?=?0.85), and 1.15 (95% CI 0.62-2.13; p?=?0.57), respectively; with an overall RR of 1.09 (95% CI 0.70-1.70; p?=?0.48) for mortality.<h4>Conclusions</h4>DOACs appears to be non-inferior or at least as effective as warfarin in the treatment of left ventricular thrombus without any statistical difference in stroke or bleeding complications.
Project description:Venous thromboembolism (VTE) is highly prevalent in patients with cancer. Non-vitamin K antagonist oral anticoagulants (NOACs), directly targeting the enzymatic activity of thrombin or factor Xa, have been shown to be as effective as and safer than traditional anticoagulation for VTE prophylaxis in no-cancer patients. However, related studies that focused on the anticoagulation in cancer patients are lacked, and almost no net clinical benefit (NCB) analyses that quantified both VTE events and bleeding events have been addressed in this fragile population. Therefore, we aim to investigate this issue using a systematic review and NCB analysis. A comprehensive search of Medline, Embase, and Cochrane Library were performed for randomized controlled trials (RCTs) that reported the VTE events and major bleeding of NOACs and traditional anticoagulants in patients with or without cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) of VTE and bleeding events were calculated using a random-effects model. The primacy outcome of narrow NCB was calculated by pooling ORs of VTE and major bleeding, with a weighting of 1.0. Similarly, the broad NCB was calculated by pooling ORs of VTE and clinically relevant bleeding. Heterogeneity was assessed through I2 test and Q statistic, and subgroup analyses were performed on the basis of different patients (VTE patients or acutely ill patients), comparators (vitamin-K antagonists or low-molecular-weight heparin), and follow-up duration (?6 months or >6 months). Overall, 9 RCTs including 41,454 patients were enrolled, of which 2,902 (7%) were cancer patients, and 38,552 (93%) were no-cancer patients; 20,712 (50%) were administrated with NOACs and 20,742 (50%) were administrated with traditional anticoagulants. The use of NOACs had a superior NCB than traditional anticoagulation in both cancer patients (OR: 0.68, 95%CI: 0.50-0.85 for narrow NCB; OR: 0.76, 95%CI: 0.61-0.91 for broad NCB) and no-cancer patients (OR: 0.75, 95%CI: 0.54-0.96 for narrow NCB; OR: 0.85, 95%CI: 0.67-1.04 for broad NCB), with the estimates mainly from VTE patients receiving long-term warfarin treatment. In conclusion, NOACs may represent a better NCB property compared to traditional anticoagulants in cancer patients who need long-term anticoagulation treatment.
Project description:In the past, patients with liver cirrhosis were thought to be prone to increased bleeding risk. However, those with compensated liver cirrhosis actually have normal coagulative balance, which can become altered when liver function worsens, or infection, bleeding, or acute kidney insufficiency occur. When this happens, it is now recognized that patients with liver cirrhosis are at higher risk of thrombotic rather than haemorrhagic complications. Anticoagulation plays a favourable role both when used therapeutically or prophylactically. Successful anticoagulation is associated with a lower rate of decompensation and with improved survival. To date, treatment has involved the use of low molecular weight heparins and vitamin K antagonists. Preliminary data suggest that novel non-vitamin K antagonist oral anticoagulants can be used safely in patients with liver cirrhosis.
Project description:BACKGROUND:The role of anticoagulation therapy for stroke prevention in older atrial fibrillation (AF) patients with chronic kidney disease (CKD) remains unclear. Therefore, we conducted a meta-analysis to explore the efficacy and safety of anticoagulation therapy in this population. METHODS:The Cochrane Library, PubMed, and Embase databases were systematically searched for studies reporting the effect of anticoagulation therapy in older patients with AF and CKD. The risk ratios (RRs) and 95% confidence intervals (CIs) were regarded as the risk estimates. A random-effects model selected was to evaluate the treatment outcomes. The presentations were based on the Preferred Reporting Items for reporting systematic reviews and meta-analyses statement. RESULTS:A total of 7 studies with 24,794 older patients with AF and CKD were included. The follow-up of the included studies ranged from 0.9 to 9.0 years. In older patients with no dialysis, compared with nonanticoagulants, anticoagulants reduced the risk of all-cause death (RR 0.66, 95% CI 0.54-0.79), but had comparable risks of ischemic stroke/transient ischemic attack (TIA, RR 0.91, 95% CI 0.46-1.79) and bleeding (RR 1.17, 95% CI 0.86-1.60). In older patients with dialysis, compared with nonanticoagulants, anticoagulants increased the risk of bleeding (RR 1.37, 95% CI 1.09-1.74), but had similar risks of ischemic stroke/TIA (RR 1.18, 95% CI 0.88-1.58) and death (RR 0.87, 95% CI 0.60-1.27). CONCLUSION:Compared with nonanticoagulation, anticoagulation therapy is associated with a reduced risk of death in older AF patients with nondialysis, but an increased risk of bleeding in older patients with dialysis.
Project description:IMPORTANCE:Atrial fibrillation (AF) during sepsis is associated with an increased risk of ischemic stroke during hospitalization, but risks and benefits associated with anticoagulation for AF during sepsis are unclear. OBJECTIVE:To determine clinician practice patterns and patient risk of stroke and bleeding associated with use of anticoagulation for AF during sepsis. DESIGN, SETTING, AND PARTICIPANTS:A retrospective cohort study using enhanced administrative claims data from approximately 20% of patients hospitalized in the United States July 1, 2010, to June 30, 2013, examined patients with AF during sepsis who did not have additional indications for therapeutic anticoagulation. Propensity score and instrumental variable analyses were used to evaluate risks of in-hospital stroke and bleeding associated with anticoagulation during sepsis. EXPOSURES:Parenteral anticoagulants administered in doses greater than those used for prophylaxis of venous thromboembolism. MAIN OUTCOMES AND MEASURES:Ischemic stroke and clinically significant bleeding events during hospitalization. RESULTS:Of 113?511 patients hospitalized with AF and sepsis, 38?582 were included in our primary analysis (18?976 men and 19?606 women; mean [SD] age, 74.9 [11.7] years). A total of 13?611 patients (35.3%) received parenteral anticoagulants, while 24?971 (64.7%) did not. Hospital utilization rates of parenteral anticoagulants for AF during sepsis varied (median, 33%; 25th-75th percentile, 25%-43%). CHA2DS2VASc scores (congestive heart failure, hypertension, age ?75 years [doubled], type 1 or type 2 diabetes, stroke or transient ischemic attack or thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) poorly discriminated the risk of ischemic stroke during sepsis (C statistic, 0.526). Among 27?010 propensity score-matched patients, rates of in-hospital ischemic stroke events did not differ significantly between patients who did (174 of 13?505 [1.3%]) and did not (185 of 13?505 [1.4%]) receive parenteral anticoagulation (relative risk [RR], 0.94; 95% CI, 0.77-1.15). Clinically significant bleeding occurred more often among patients who received parenteral anticoagulation (1163 of 13?505 [8.6%]) than patients who did not receive parenteral anticoagulation (979 of 13?505 [7.2%]; RR, 1.21; 95% CI, 1.10-1.32). Risk of ischemic stroke associated with parenteral anticoagulation did not differ significantly between patients with preexisting (RR, 1.12; 95% CI, 0.86-1.44) or newly diagnosed AF (RR, 0.85; 95% CI 0.57-1.27; P?=?.31 for interaction). Results were robust to multiple sensitivity analyses, including hospital utilization rates of parenteral anticoagulation for AF as an instrument for anticoagulation exposure (RR for stroke, 1.08; 95% CI, 0.62-1.90; RR for bleeding, 1.23; 95% CI, 0.88-1.72). CONCLUSIONS AND RELEVANCE:Among patients with AF during sepsis, parenteral anticoagulation was not associated with reduced risk of ischemic stroke and was associated with higher bleeding rates.