Background: While current clinically administered anticoagulant medications have demonstrated effectiveness, they have also precipitated significant risks: severe bleeding complications including, but not limited to, gastrointestinal hemorrhaging and intracranial and other life-threatening major bleedings. An ongoing effort is being made to identify the best targets for anticoagulant-targeted drugs. Coagulation factor XIa (FXIa) is emerging as an important target of current anticoagulant treatment. Objective: This review will summarize the development of anticoagulants and recent advances in clinical trials of experimental factor XI inhibitors from a clinical application perspective. Results: As of 1 January 2023, our search screening included 33 clinical trials. We summarized the research progress of FXIa inhibitors from seven clinical trials that evaluated their efficacy and safety. The results showed no statistically meaningful distinction in the primary efficacy between patients receiving FXIa inhibitors compared to controls (RR = 0.796; 95% CI: 0.606–1.046; I2 = 68%). The outcomes did not indicate a statistical difference in the occurrence of any bleeding between patients receiving FXIa inhibitors compared to controls (RR = 0.717; 95% CI: 0.502–1.023; I2 = 60%). A subgroup analysis found significant differences in severe bleeding and clinically relevant hemorrhaging in subjects receiving FXIa inhibitors compared to Enoxaparin (RR = 0.457; 95% CI: 0.256–0.816; I2 = 0%). Conclusions: Clinical trials to date have indicated that factor XIa is a potential anticoagulation target, and factor XIa inhibitors may play an important role in the development of anticoagulants.
IntroductionNovel oral anticoagulants (NOACs) have been used in antithrombotic therapy in patients with cancer, and their efficacy and safety have been evaluated in several meta-analyses. Although a large body of findings has accumulated to support the benefit of NOACs for the treatment and prevention of cancer-associated thromboembolism, there is no convincing evidence because of inconsistent results across studies and questionable data quality. Its efficacy and safety remain controversial, especially with regard to the risk of bleeding.Methods and analysisWe will search PubMed, Embase and Web of science, Cochrane Library on 19 April 2022 (searches will be updated until complete) to identify systematic reviews, meta-analyses and pooled analyses of the efficacy and safety of NOACs for the treatment of cancer-associated venous thromboembolism. The quality of eligible systematic evaluations will be measured by A Measurement Tool to Assess Systematic Reviews. For each outcome, if a random effects model is not used, we will extract the data and estimate a 95% CI using the random effects model approach. For each random effects estimate, a 95% prediction interval is calculated. Heterogeneity between studies will be quantified using the I2metric. In addition, if an assessment contains at least three articles, we will reanalyse the assessment using Egger’s asymmetry test to detect and visualise possible publication bias in the articles.Ethics and disseminationNo formal ethical approval is required since we will use publicly available data. We will disseminate the findings of the umbrella review through publication in a peer-reviewed journal and conference presentations.PROSPERO registration numberCRD42022342053.
BACKGROUND: Currently, the frequency of coagulation dysfunction associated with Chimeric antigen receptor-T cell (Car-T) therapy cannot yet be determined. OBJECTIVE: We performed a systematic review and meta-analysis to examine the prevalence of abnormal laboratory tests related to coagulation disorders in patients receiving Car-T therapy and provide a reference for future risk assessment mechanisms. METHODS: We searched PubMed, Embase, and Web of Science for relevant studies and evaluated their quality using the methodology index of non-random research (MINORS). 2672 quotations were retrieved via systematic searches. After screening of titles, abstracts and full-text, 45 trials involving 2541 patients were ultimately included. 41 studies reported the incidence of thrombocytopenia, 8 studies reported the rate of low fibrin, 4 trials reported the rate of APTT or PT abnormalities and only 3 trials reported the incidence of venous thromboembolism (VTE). We performed a quantitative meta-analysis to explore the incidence of thrombocytopenia following Car-T treatment. The incidence of hypofibrinogenemia, VTE, and abnormal APTT or PT was only qualitatively assessed, as fewer reports were included in this study. RESULTS: The overall incidence of thrombocytopenia associated with Car-T therapy was 45.8% (95%[CI], 0.384–0.533). The highest rates of thrombocytopenia occurred in patients with multiple myeloma (60.1%, 95%[CI], 0.507–0.688) and aged between 18 to 60 (50%, 95%[CI], 0.367–0.633). There was greater prevalence of thrombocytopenia in BCMA-Car-T therapy of 58.7% (95%[CI], 0.482–0.685). Thrombocytopenia occurred most frequently in Car-T patients treated with a dosage of 1 × 105–1 × 106 cell/kg, at a rate of 66.2% (95%[CI], 0.561–0.749). CONCLUSION: Overall, 45.8 percent of patients receiving Car-T treatment suffered from thrombocytopenia. Multiple myeloma patients, ages between 18–60, a dose of 1 × 105–1 × 106 cell/kg and BCMA-Car-T therapy are all considered high-risk factors.
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