Seminars in thrombosis and hemostasis最新文献

The optimal pharmacological prophylaxis for venous thromboembolism (VTE) after hip or knee arthroplasty is uncertain. We conducted a systematic review and network meta-analysis to compare the efficacy and safety of various medications. We searched multiple databases for randomized clinical trials (RCTs) comparing medications (including factor Xa inhibitors, factor IIa inhibitor, warfarin, unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], aspirin, pentasaccharide) for VTE prophylaxis post-arthroplasty. Outcomes included any postoperative VTE identified with screening, major bleeding, and death. We used LMWH as the main comparator for analysis and performed trial sequential analysis (TSA) for each pairwise comparison. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessments, Developments and Evaluations). We analyzed 70 RCTs (55,841 participants). Factor Xa inhibitors decreased postoperative VTE significantly compared with LMWH (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.44-0.68, high certainty). Pentasaccharides probably reduce VTE (OR: 0.61, 95% CI: 0.36-1.02, moderate certainty), while the factor IIa inhibitor dabigatran may reduce VTE (OR: 0.75, 95% CI: 0.40-1.42, low certainty). UFH probably increases VTE compared with LMWH (OR: 1.31, 95% CI: 0.91-1.89, moderate certainty), and other agents like warfarin, aspirin, placebo, and usual care without thromboprophylaxis increase VTE (high certainty). Factor Xa inhibitors may not significantly affect major bleeding compared with LMWH (OR: 1.06, 95% CI: 0.81-1.39, low certainty). No medications had a notable effect on mortality compared with LMWH (very low certainty). TSA suggests sufficient evidence for the benefit of factor Xa inhibitors over LMWH for VTE prevention. Compared with LMWH and aspirin, factor Xa inhibitors are associated with reduced VTE after hip or knee arthroplasty, without an increase in bleeding and likely no impact on mortality.

Intravenous direct thrombin inhibitors (DTIs) are used for thromboembolic disorders. This systematic review aims to characterize intravenous DTI agents, dosing, monitoring strategies (or use), bleeding, and mortality, in pediatric patients with acute venous thromboembolism (VTE) or heparin-induced thrombocytopenia with thrombosis (HITT). MEDLINE, Embase, and Cochrane's CENTRAL were searched from inception through July 2023. Case series, retrospective studies, and prospective studies providing per-patient or summary data for patients < 18 years of age with VTE or HITT treated with an intravenous DTI were included. Selection and data extraction were conducted independently by two reviewers. Sixteen studies (7 case reports, 1 case series, 5 retrospective studies, 3 prospective studies) with 85 patients were included. Target conditions included acute VTE in 54 (64%) and HITT in 31 (36%) patients. Bivalirudin, argatroban, and lepirudin were used in 52 (61%), 27 (32%), and 6 (7%) patients, respectively. Fifty-two (61%) patients received a bolus dose, and weighted mean infusion rates for bivalirudin, argatroban, and lepirudin were 0.2 mg/kg/hr, 1.2 mcg/kg/min, and 0.15 mg/kg/hr, respectively. The activated partial thromboplastin time was utilized for monitoring in 82 (96%) patients. Complete or partial thrombus resolution was reported in 53 (62%) patients, mortality in 6 (7%) patients, and bleeding complications in 14 (16%) patients. In this systematic review involving 85 pediatric patients treated with an intravenous DTI for acute VTE or HITT, bivalirudin was the most commonly utilized agent, with a rate of resolution over 60% despite a high acuity in the population studied. Prospective collaborative studies are warranted to establish optimal dosing and further characterize VTE and bleeding outcomes.

An increasing number of Mendelian randomization (MR) studies have evaluated the causal link between smoking and venous thromboembolism (VTE). However, previous studies often rely on single genetic variants related to smoking quantity and exhibit various other shortcomings, making them prone to pleiotropy and potentially leading to imprecise causal estimates. Thus, the deeper causal mechanisms remain largely unexplored. This MR study reassessed the causal relationship between smoking and VTE, including its subtypes-deep vein thrombosis (DVT) and pulmonary embolism (PE). Data on VTE were sourced from the FinnGen consortium with nonoverlapping sample sizes. The smoking phenotypes analyzed included smoking initiation, lifetime smoking, the number of cigarettes smoked per day by both current and former smokers (CigDay), and total pack-years of smoking in adulthood. The primary analytical method was inverse-variance-weighted (IVW), supplemented by multiple verification methods to ensure robust results. Statistical rigor was ensured through LDtrait pruning and Steiger filtering for reverse causation, with comprehensive sensitivity analyses including RadialMR confirming the findings' robustness. After Bonferroni correction, this study demonstrates significant causal evidence linking lifetime smoking with the incidence of VTE (odds ratio [OR]_IVW = 1.50, 95% confidence interval [CI] 1.21-1.85, p = 1.75 × 10^-4) and PE (OR_IVW = 1.69, 95% CI 1.25-2.28, p = 6.55 × 10^-4), and suggestive evidence with DVT, consistent in direction with previous studies but showing considerable differences in effect sizes and significance. Additionally, CigDay (past and current) increases the risks of VTE and DVT, while no causal link was found between smoking initiation and VTE or its subtypes (p < 0.05), both directly contradicting previous conclusions. Furthermore, our study is the first to suggest a causal link between pack-years and an increased risk of VTE. This MR study employed rigorous statistical pruning of its instrumental variables, using the most comprehensive smoking phenotype to date. It successfully mitigated biases such as winner's curse, yielding causal effect results distinct from previous studies.

Congenital heart disease (CHD) is a risk factor for thromboembolism (TE). Data describing the rate of, and risk factors associated with, recurrent TE in children with CHD are limited. We prospectively evaluated TE recurrence risk in children with CHD and acute TE and investigated clinical risk factors associated with recurrent TE. Patients < 21 years of age with CHD and acute TE were enrolled in a single-institutional prospective inception cohort study (July 2013-April 2024). Descriptive statistics summarized variables including CHD and thrombus characteristics, antithrombotic regimens, bleeding, and recurrent TE. Multivariable logistic regression determined risk factors for recurrent TE. Among 40 children with CHD and acute TE, 13 (33%) developed ≥ 1 recurrent TE (arterial n = 1 [6%], venous n = 15 [83%], venous + arterial n = 2 [11%]) at a median time of 86 (interquartile range, 45-112) days postdiagnosis of the index TE. One-year cumulative incidence of recurrent TE was 38%. Twelve (67%) recurrent TE events were central venous catheter (CVC)-related. In univariable analyses, immobility (46% vs. 7%, p = 0.01), the presence of a CVC (69% vs. 30%, p = 0.02), and lower extremity index venous TE (89% vs. 41%, p = 0.04) were associated with TE recurrence. After adjustment for other potential risk factors via multivariable logistic regression, immobility (adjusted odds ratio [OR] 13.2, 95% confidence interval [CI] 1.16-151.3, p = 0.04) and the presence of a CVC (adjusted OR 5.28, 95% CI 1.03-27.1, p = 0.05) remained as independent risk factors for recurrent TE. The 1-year risk of TE recurrence was high among pediatric patients with CHD and acute TE. Immobility and the presence of CVC were independent risk factors for recurrent TE. Multicenter prospective cohort studies are warranted to substantiate and expand upon these important findings.

Long coronavirus disease 2019 (COVID-19)-a postacute consequence of severe acute respiratory syndrome coronavirus 2 infection-manifests with a broad spectrum of relapsing and remitting or persistent symptoms as well as varied levels of organ damage, which may be asymptomatic or present as acute events such as heart attacks or strokes and recurrent infections, hinting at complex underlying pathogenic mechanisms. Central to these symptoms is vascular dysfunction rooted in thrombotic endothelialitis. We review the scientific evidence that widespread endothelial dysfunction (ED) leads to chronic symptomatology. We briefly examine the molecular pathways contributing to endothelial pathology and provide a detailed analysis of how these cellular processes underpin the clinical picture. Noninvasive diagnostic techniques, such as flow-mediated dilation and peripheral arterial tonometry, are evaluated for their utility in identifying ED. We then explore mechanistic, cellular-targeted therapeutic interventions for their potential in treating ED. Overall, we emphasize the critical role of cellular health in managing Long COVID and highlight the need for early intervention to prevent long-term vascular and cellular dysfunction.

Catastrophic thrombosis is a severe condition characterized by a hypercoagulable tendency, leading to multiple thromboembolic events in different blood vessels, usually within a short timeframe. Several conditions have been associated with the development of catastrophic thrombosis, including the catastrophic antiphospholipid syndrome, thrombotic anti-platelet factor 4 immune disorders, thrombotic microangiopathies, cancers, the hyper-eosinophilic syndrome, pregnancy, infections, trauma, and drugs. Thrombotic storm represents a medical emergency whose management represents a serious challenge for physicians. Besides the prompt start of anticoagulation, a patient's prognosis depends on early recognition and possible treatment of the underlying condition. In this narrative review, we summarize the main characteristics of catastrophic thrombosis, analyzing the various conditions triggering such life-threatening complication. Finally, an algorithm with the diagnostic workup and the initial management of patients with catastrophic thrombosis is presented.