Journal of Thrombosis and Thrombolysis最新文献

Extended anticoagulation is recommended for venous thromboembolism (VTE) patients at high recurrence risk. However, the optimal long-term dosing strategy for direct oral anticoagulants (DOACs) remains uncertain. This meta-analysis compares the efficacy and safety of reduced-dose versus full-dose DOACs during extended-phase VTE treatment. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing reduced-dose (apixaban 2.5 mg BID or rivaroxaban 10 mg QD) and full-dose (apixaban 5 mg BID or rivaroxaban 20 mg QD) DOACs. Searches were performed in PubMed, Cochrane CENTRAL, Embase and Scopus till June 10, 2025. Outcomes included recurrent VTE, major bleeding, clinically relevant non-major bleeding (CRNMB), and all-cause mortality. Risk ratios (RRs) were pooled using random-effects models. Five RCTs comprising 8,781 patients were analyzed. Reduced-dose DOACs significantly lowered major bleeding risk (RR: 0.62; 95% CI: 0.42-0.92; p = 0.02; I² = 12%) and CRNMB (RR: 0.75; 95% CI: 0.63-0.88; p = 0.0006; I² = 0%) compared to full-dose DOACs. No significant differences were observed between the groups in recurrent VTE (RR: 0.94; 95% CI: 0.68-1.29; p = 0.70; I² = 0%) or all-cause mortality (RR: 0.86; 95% CI: 0.63-1.17; p = 0.35; I² = 42%). No significant differences across outcomes were observed between cancer-associated and general VTE populations. Reduced-dose DOACs significantly lower bleeding risk without compromising efficacy in preventing recurrent VTE. These findings support the preferential use of reduced-dose DOACs as a safer and effective option for extended anticoagulation, especially in patients at elevated bleeding risk.

Congenital fibrinogen disorders (CFD) are characterized by heterogeneous manifestations, from asymptomatic to severe bleeding or thrombosis, associated with genetic mutations in FGA, FGB, or FGG genes. As a result, diagnosis is challenging, particularly in low- and middle-income countries, where evidence is scarce. The aim of this review is to describe the distribution of CFD-associated genetic mutations across different regions of the world and their corresponding phenotypes. Data from MEDLINE and the French Group for the Study of Hemostasis and Thrombosis databases were qualitatively organized based on the United Nations regional classification. A total of 132 studies on CFD were selected from MEDLINE and GFHT fibrinogen database, comprising over 1000 mutations descriptions and approximately 340 unique mutations. FGA mutations are most associated with dys- or afibrinogenemia, while FGB mutations are associated with hypo- or afibrinogenemia and FGG with dys- or hypofibrinogenemia Across countries, the most common mutations in afibrinogenemia and hypofibrinogenemia were intronic variant sequence in FGA, p. Arg47stop in FGB, and mutations in exon 8 of FGG. Dysfibrinogenemia was associated with mutations in exon 2 of FGA, typically resulting in asymptomatic individuals and with mutations in exon 8 of FGG, which are associated with thrombosis. The majority of mutations related to CFD and their associated phenotypes have been reported in Western Europe, North America and East Asia. Evidence from Latin America, Southeast Asia, and Africa remains limited, with Brazil having only one study that evaluated CFD mutations. Data on CFD phenotypes and associated genetic mutations from low and middle income countries are necessary to ensure equity in the management of these rare diseases.t.

Current treatments for venous thromboembolism include warfarin, various heparins, and direct oral anticoagulants. While effective, there's ongoing research for safer alternatives, especially for high-risk patients (e.g., cancer, post-operative, and those with end-stage renal disease). Factor XI has been identified as crucial in abnormal thrombosis but less so in normal hemostasis, suggesting that inhibiting it could reduce thrombosis while also limiting bleeding risks. Recent phase 2 trials on factor XI inhibitors show promise for preventing venous thromboembolism in patients undergoing total knee arthroplasty, in cancer patients, and in patients with end-stage renal disease. Three key unmet needs include: need for large-scale phase 3 clinical trials, broader surgical applications and management of bleeding complications/reversal strategies. Further research on these aspects is essential, especially as factor XI inhibitors progress towards clinical use.

Coronary atherosclerotic plaques can lead to acute coronary syndrome (ACS) occurrence through three main mechanisms: plaque rupture, plaque erosion and calcified nodule. Many destabilized plaques, however, do not cause cardiovascular events. Instead, thrombus formation is confined, lumen patency is preserved and the arterial wall is restored in a process termed as plaque healing. Early studies regarding coronary plaque healing used arterial specimens to determine its prevalence and histological characteristics. Advances in imaging modalities later enabled the implementation of in vivo studies, which have used optical coherence tomography (OCT) to identify the repaired plaques. They are visualized as lesions with a heterogeneous signal-rich layered or multilayered pattern and a distinct optical density from underlying plaque components. On one hand, plaque healing acts as a protective mechanism against myocardial infarction and unstable angina. On the other hand, the presence of layered plaques indicates previous plaque destabilization and therefore increased cardiovascular risk. Clinicians ought to bear these in mind in order to better apply patient risk stratification and adjust medical interventions. The aim of this review is to discuss the physiology of coronary plaque healing, determine its prevalence and clinical significance, as well as propose possible pathophysiological mechanisms behind impaired plaque healing along with therapeutic options.

Optimal antiplatelet therapy is crucial in percutaneous coronary intervention (PCI) to balance thrombotic and bleeding risk. Cangrelor, a rapid-acting intravenous P2Y12 inhibitor, is particularly effective in high-risk PCI scenarios, including acute coronary syndrome (ACS) or patients unable to take oral medications. The SMILE study evaluated real-world timing, indications, and outcomes of cangrelor use, along with transition to oral P2Y12 inhibitors, in high-risk patients undergoing PCI. A retrospective analysis of Mount Sinai PCI registry was conducted, examining consecutive patients receiving cangrelor from January 2018 to March 2024. Transition to oral P2Y12 inhibitors (ticagrelor, clopidogrel, or prasugrel) followed institutional protocols based on guidelines and expert consensus. The primary endpoint was in-hospital major adverse cardiac and cerebrovascular events (MACCE), including myocardial infarction, stroke, and all-cause death. Among 493 patients, 78.7% presented with ACS (29.6% STEMI; 14.8% cardiogenic shock) and 79.3% underwent complex PCI. Of these, 80.5% were subsequently transitioned to ticagrelor (N=397) and 19.5% to a thienopyridine (clopidogrel N=85, prasugrel N=11). MACCE incidence was 12.6%, while bleeding occurred in 4.3%. A lower risk of MACCE was associated with transition to ticagrelor (9.8% vs. 24.0%; adjusted OR 0.35, 95%CI 0.20-0.62, p < 0.001) and adherence to protocol for transition to oral P2Y12 inhibitors (10.9% vs. 19.4%; adjusted OR 0.51, 95%CI 0.28-0.94). Extended low-dose cangrelor infusion was well-tolerated in critically ill patients requiring prolonged parenteral antiplatelet therapy. Overall, the SMILE study demonstrated that adherence to standardized transition protocols enhances clinical outcomes in high-risk PCI patients receiving cangrelor, particularly when transitioned to ticagrelor. Further research is needed to validate these results across diverse populations and clinical settings.

The von Willebrand factor/ADAMTS13 ratio and shortened PFA-100 values have been associated with the risk of venous thromboembolism (VT). Our objective was to confirm the association of the VWF/ADAMTS13 ratio with VT risk and to assess the correlation between this ratio and PFA-100 values. We determined ADAMTS13 and VWF plasma levels, as well as PFA-100 values in 800 individuals (400 with VT and 400 healthy controls) from the RETROVE project. Using binary logistic regression and multivariate analyses, we evaluated the relationship between the VWF/ADAMTS13 ratio and VT risk. Quartile cut-offs of this ratio were calculated in controls, after which we estimated odds ratios (ORs) with 95% CIs. The risk of VT increased progressively with increasing quartiles of the VWF/ADAMTS13 ratio, with an OR of 4.12 (95% CI, 2.47-6.88) for the highest vs lowest quartiles in an age-adjusted analysis. When we analyzed the ROC curve for the VWF/ADAMTS13 ratio, we found similar results: we obtained three ranges of this ratio, with an increasingly progressive risk (ORs from 2.59 to 6.54). Values of the VWF/ADAMTS13 ratio correlated negatively with PFA-100 (R = - 0.5 p < 0.001). These findings indicate that the VWF/ADAMTS13 ratio is an indicator of VT risk and that a high ratio correlates negatively with PFA-100 values.