Journal of Thrombosis and Thrombolysis最新文献

Introduction: The association between moderate-to-vigorous physical activity (MVPA) and recurrent venous thromboembolism (VTE) is unclear, but an improved understanding could inform behavioral health recommendations.

Methods: The Heart and Vascular Health study, set in a large integrated healthcare system, identified adults with a validated incident VTE between January 2002 and December 2010. An inception cohort was formed from these cases and followed for a first recurrent VTE through December 2014. Usual MVPA pre-incident VTE was self-reported by 1381 adults via telephone interview, and MVPA amount was calculated in metabolic equivalent of task (MET) hours (h) per week. Multivariable-adjusted Cox proportional hazards models estimated adjusted hazard ratios (HR_adj) for any MVPA versus none and MVPA amount, continuously and in quartiles, in MET-h/week among participants reporting any MVPA. Secondary analyses separately evaluated MET-h/week, by intensity.

Results: During follow-up (median = 5.23 years), 288 (20.9%) individuals developed a recurrent VTE. There was no evidence of an association between any MVPA versus none and VTE recurrence (HR_adj=1.24, [95% confidence interval [CI]: 0.80, 1.91]). Among participants with any MVPA, there was no evidence of an association between MVPA in MET-h/week (HR_adj per 7.5 MET-h/week = 1.00, [95% CI: 0.98, 1.03]), nor quartiles of MVPA (p-trend = 0.62) with VTE recurrence risk. In secondary analyses there was no evidence of an association of MET-h/week of moderate or vigorous physical activity (PA) with VTE recurrence.

Conclusions: In this cohort of adults who experienced incident VTE, there was no evidence of an association between self-reported MVPA pre-incident VTE and VTE recurrence risk.

Autoimmune acquired factor XIII deficiency (AiF13D) is an exceptionally rare and serious bleeding disorder. This condition may occur idiopathically or in association with comorbidities, such as malignancies or autoimmune diseases. Data comparing these distinct etiological subgroups remain limited. Therefore, we conducted a systematic literature review of published case reports, case series, and cohort studies on AiF13D indexed in PubMed, Web of Science, and Scopus up to December 2023. We compared the clinical characteristics, treatment modalities, and outcomes between patients with AiF13D associated with underlying disorders and those with idiopathic AiF13D. Our analysis revealed a higher proportion of female patients in the AiF13D group with underlying diseases compared to the idiopathic group. Statistically significant differences were observed that patients with underlying diseases exhibited slightly higher inhibitor levels and a greater frequency of Grade III bleeding events. Furthermore, fewer AiF13D patients with underlying diseases received combination therapy (prednisone plus rituximab or cyclophosphamide) compared to the idiopathic group. Additionally, this group experienced higher rates of relapse and/or mortality. Collectively, these findings indicated that AiF13D patients with underlying diseases experience more severe bleeding manifestations and poorer outcomes. Consequently, clinicians managing concomitant conditions should maintain vigilance for potential AiF13D development. Regular monitoring of FXIII activity and inhibitor titers is essential, coupled with prompt initiation of anti-inhibitor therapy when indicated.

Platelets are small, anuclear cells crucial for hemostasis, coagulation, immune responses, and vascular diseases. While unable to produce their own RNA, platelets inherit RNA from their megakaryocyte precursors, exchange RNA with other cells, and possess all the necessary machinery for protein synthesis. However, several challenges, including their limited RNA content, high reactivity of these small cells leading to their activation, have hindered single-cell transcriptomic studies of these cells. The primary objective of this study is to perform single-cell RNA sequencing (scRNA-seq) on platelets obtained from whole blood. Peripheral whole blood from a healthy donor was obtained by venipuncture and was purified to obtain platelet-rich plasma (PRP). ScRNA-seq was performed using the 10X genomics platform on PRP for the first time. Data normalization and UMAP clustering with cluster-specific differential gene expression analysis were performed. ScRNA-seq performed on platelets identified three distinct clusters, with one enriched for platelet-specific lineage markers, such as PPBP and PF4. Mitochondrial RNA was highly expressed accounting for approx. 14% of the total RNA counts. Despite procedural challenges and technical considerations including high exhaustion potential and sensitivity to handling, small cell size and limited RNA content, this pilot study demonstrates feasibility of scRNA-seq of platelets from whole blood. This advancement paves the way for groundbreaking insights into platelet biology and more focus for clinician researchers on potential research avenues.

Clinical practice guidelines on the optimal thromboprophylaxis duration following total hip and knee arthroplasty (THA and TKA) and hip fracture surgery are inconsistent. The aim of this meta-analysis is to investigate the effect of pharmacological prophylaxis duration on postoperative venous thromboembolism (VTE) in these patients. The primary outcome was the incidence of symptomatic and confirmed VTE at three months following surgery. A systematic search was performed in MEDLINE Complete (EBSCO), Embase, CINAHL complete (EBSCO), Web of Science and in CENTRAL databases, for randomised controlled trials comparing extended (minimum 28 days for THA and 10 days for TKA) vs. shorter duration thromboprophylaxis or placebo following these operations. Fifteen trials with a total of 26,580 participants were identified. Compared to shorter prophylaxis, extended thromboprophylaxis reduced 90-day symptomatic and confirmed VTE (OR: 0.43; 95% CI: 0.26-0.72; P = 0.001, I² = 0%; P = 0.75, respectively), significant only in the THA subgroup (P = 0.002). Beneficial effects were also observed with 30-day deep venous thrombosis (DVT) (OR: 0.32; 95% CI: 0.20-0.50; P < 0.001) and proximal DVT incidence (OR: 0.22; 95% CI: 0.12-0.41; P < 0.001) following THA. There were insufficient data to support extended prophylaxis for hip fracture surgery or TKA. Extending thromboprophylaxis up to 25-35 days appeared to reduce the incidence of 90-day symptomatic and confirmed VTE, particularly after THA. However, contemporary perioperative protocols, including early mobilisation and risk stratification, must be considered in determining optimal prophylaxis duration.

Hemophilia A and B are X-linked bleeding disorders caused by mutations in the F8 and F9 genes, resulting in deficiencies of coagulation factors VIII (FVIII) and IX (FIX), respectively. A major complication of replacement therapy is the development of neutralizing antibodies (inhibitors), which occur in approximately 30% of patients with severe hemophilia A and about 3% of those with hemophilia B. The role of missense and nonsense mutations in inhibitor formation has been increasingly recognized. In hemophilia A, missense mutations within immunogenic domains may alter FVIII structure, eliciting immune responses. Nonsense mutations especially those located in the light chain are associated with higher inhibitor risk due to the production of truncated, non-functional proteins. In hemophilia B, missense mutations rarely result in inhibitor development, whereas nonsense mutations and large deletions carry a significantly higher risk. Molecular genotyping contributes to predicting inhibitor formation and supports individualized treatment planning.

Pulmonary embolism (PE) is a life-threatening condition often treated with unfractionated heparin (UFH) in intermediate high-risk patients. Activated Partial Thromboplastin Time (aPTT) is used to monitor UFH efficacy. We sought to evaluate the correlation between time in therapeutic range (TTR) and prognosis in patients with pulmonary embolism treated with unfractionated heparin. A prospective cohort study included 203 patients admitted to a tertiary care center between July 2019 and August 2024 with a confirmed diagnosis of intermediate risk PE treated with UFH. TTR was calculated based on aPTT values during the first 72 h of hospitalization. The correlation between TTR and mortality rates was assessed. Out of the 203 patients, 116 (57%) achieved therapeutic range at least once, with a mean TTR of 43.1% (± 22.4) and a median of 39%. Nevertheless, the overall mean TTR for all patients was 24.6% (± 27.3), with a median of 18.8%. During the study period 25 (12.3%) patients have died, of them 9 (4.4%) within 30 days and 16 (7.9%) within one year. Higher TTR was associated with reduced 30-day (p = 0.051) and one-year (p = 0.045) mortality rates. Receiver Operating Characteristic (ROC) analysis identified a TTR threshold of 21.5% for predicting one-year mortality, demonstrating a high negative predictive value (NPV) of 96.8% but a low positive predictive value (PPV) of 12%. Patients with acute PE who achieved higher TTR exhibited better outcomes at 30 days and one year. However, most patients did not reach adequate TTR levels, leaving its role as an independent prognostic indicator uncertain. Larger studies are necessary to optimize therapeutic strategies and improve outcomes in intermediate-risk PE patients.

Data on direct oral anticoagulants (DOACs) in venous thrombotic antiphospholipid antibody syndrome (APS) are controversial. This pilot study aimed to assess the safety and efficacy of DOACs in APS patients requiring oral anticoagulation for venous thromboembolism (VTE) but unsuitable for treatment with vitamin K antagonists (VKAs). We performed a prospective multi-centre case-series including APS patients with previous VTE who were receiving treatment with DOACs due to ineligibility for VKAs. Main outcomes were bleeding, arterial and recurrent venous thrombotic events and all-cause death. We included 18 patients (median age 59.6 years, 66.7% women). The antiphospholipid antibody pattern was single positivity for 33.3% patients, double positivity for 33.3%, and triple positivity for 27.8%. Only one patient had seronegative APS. Apixaban, dabigatran, rivaroxaban and edoxaban were prescribed in 44.4%, 27.8%, 16.7% and 11.1% of patients, respectively. The mean follow-up was 50.1 ± 24.1 months. During the observation period, no recurrent VTE episodes or arterial thrombotic events were recorded. Four bleedings, of which 2 major, were reported. The incidence rate of bleeding was 5.3 per 100 patient-years (95% confidence interval [95%CI] 1.4-13.6). No intracranial bleedings were recorded.In conclusion, our preliminary findings may suggest DOAC as possible option for patients with venous thrombotic APS unsuitable to VKAs. Although these findings are promising, larger cohort studies are needed to confirm this finding.

Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is a significant cause of disability and mortality. While endovascular thrombectomy (EVT) is the standard treatment, microvascular reperfusion remains a challenge. Although there is mixed information about the safety and effectiveness of tirofiban, a glycoprotein IIb/IIIa inhibitor, it may improve perfusion when administered before EVT. Its effects on risks and functional outcomes, including symptomatic intracranial hemorrhage (sICH), are investigated in this meta-analysis. We systematically searched PubMed, Embase, and Cochrane from inception to July 2025 for randomized controlled trials (RCTs) and Cohorts comparing pre-EVT tirofiban with EVT alone in LVO stroke. Primary outcomes were 90-day functional independence and the ordinal shift in mRS. Secondary outcomes included mortality and symptomatic intracerebral hemorrhage. Six Studies (1,664 patients) were included. Tirofiban did not significantly improve 90-day functional independence (RR: 1.09, 95% CI: 0.88-1.36; p = 0.44; I² = 62%) or ordinal mRS (MD: 0.06, 95% CI: -0.15 to 0.27; p = 0.58; I² = 0%). Mortality was similar between groups (RR: 0.75, 95% CI: 0.54-1.06; p = 0.11; I² = 0%). sICH risk was also comparable (RR: 0.83, 95% CI: 0.46-1.51; p = 0.55; I² = 28%). Pre-procedural tirofiban did not significantly raise the risk of sICH, improve functional outcomes, or lower death in LVO stroke patients having EVT. Although additional research may improve patient selection, these results point to limited value for routine tirofiban administration before EVT.Keypoints Pre-EVT tirofiban does not significantly improve 90-day functional outcomes in AIS due to LVO. No significant benefit was observed in ordinal modified Rankin Scale scores. Mortality and risk of symptomatic intracranial hemorrhage were similar between tirofiban and control groups. Heterogeneity was moderate to low, and findings were consistent across study types. Future studies should explore optimal patient selection, dosing strategies, and timing to identify potential subgroups that may benefit from pre-EVT tirofiban.

Early platelet-mediated re-occlusion and microvascular "no-reflow" can blunt the benefits of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Tirofiban, a short-acting GP IIb/IIIa inhibitor, may stabilize post-lysis reperfusion. Our analysis assessed the efficacy and safety of adjunct tirofiban after IVT versus IVT alone (alteplase or Tenecteplase) in patients with AIS. We conducted a meta-analysis of randomized controlled trials (RCTs) identified through searches of PubMed, Cochrane, Scopus, and Web of Science up to August 2025. Dichotomous outcomes were pooled as risk ratios (RRs), and continuous outcomes as mean differences (MDs), each with 95% confidence intervals (CIs). Three RCTs with 1,132 patients were included. Tirofiban improved excellent outcome (64.09% vs. 54.24%, RR 1.19, 95% CI 1.07 to 1.33, P = 0.002) and functional independence (80.67% vs. 70.45%, RR 1.20, 95% CI 1.04 to 1.38, P = 0.01) and reduced poor outcome (19.32% vs. 29.54%, RR 0.61, 95% CI 0.46 to 0.81, P = 0.0006). Early neurologic improvement favored tirofiban at 24-72 h (p = 0.001) but was neutral at 5-7 days (p = 0.25). Safety did not differ for any intracranial hemorrhage (ICH) (p = 0.26), asymptomatic ICH (p = 0.75), symptomatic ICH (p = 0.68), systemic bleeding (p = 0.75), or 90-day mortality (p = 0.84). Across randomized trials, adjunct tirofiban after IVT improved 90-day functional outcomes and early neurologic recovery. For safety, no statistically significant differences were observed in any ICH, asymptomatic ICH, systemic bleeding, or 90-day mortality; however, the estimate for sICH was very imprecise and does not exclude a clinically important increase. These results are exploratory and warrant confirmation in larger, multinational RCTs before informing practice.