Thrombosis and haemostasis最新文献

Dosing guidance for anticoagulation, the mainstay of venous thromboembolism (VTE) treatment, is lacking for obese children. We aimed to compare unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH) dosing requirements and clinical outcomes between obese/overweight and nonobese children.This monocentric retrospective cohort study included patients aged < 18 years old receiving anticoagulation for VTE. The outcomes were: (1) number of dose adjustments to reach therapeutic levels, (2) variation from initial dose, (3) thrombotic progression/recurrence, and (4) clinically relevant bleeding. Characteristics and dosing requirements of obese/overweight and nonobese children were compared using Pearson chi-square, Fisher exact, and Wilcoxon Mann-Whitney tests. Kaplan-Meier estimator compared the cumulative incidence of thrombotic recurrence/progression and clinically relevant bleeding between groups.We included 212 patients (median age: 6.2 years, 23.6% obese/overweight) having 258 anticoagulation encounters (LMWH: 82.6%, UFH: 17.4%). Most children had therapeutic levels following one dosage (66.7% in obese/overweight vs. 51.8% in nonobese, p = 0.201). Dosing requirements significantly differed between obese/overweight and nonobese children (average increase from initial dose: 3.2 vs. 11.3%, p < 0.001). In obese/overweight children, 11.1% of patients required ≥ 10% dose reduction versus 2.1% in nonobese children (p < 0.001). The cumulative incidence of thrombotic progression/recurrence was comparable between groups (obese/overweight: 12.0%, nonobese: 10.5%, p = 0.786). Similarly, clinically significant bleeding was rare for both groups (obese/overweight: 2.0%, nonobese: 3.1%, p = 0.609).In children treated for VTE, obesity/overweight was associated with lower anticoagulation requirements. Further prospective work is urgently needed to explore alternate regimens, such as dose capping, reduced initial dosing, or the use of fat-free mass.

Patients with atrial fibrillation (AF) often have clinical complexity phenotypes. Latent class analysis (LCA) is based on the concept of modeling of both observed and unobserved (latent) variables. We hypothesized that LCA can help in identification of AF patient groups with different risk profiles and identify patients who benefit most from the Atrial fibrillation Better Care (ABC) pathway.We studied non-valvular AF patients in the prospective multicenter COOL-AF registry. The outcomes were all-cause death, ischemic stroke/systemic embolism (SSE), major bleeding, and heart failure. Components of CHA₂DS₂-VASc score, HAS-BLED score, and ABC pathway were recorded.A total of 3,405 patients were studied. We identified 3 LCA groups from 42 variables: LCA class 1 (n = 1,238), LCA class 2 (n = 1,790), and LCA class 3 (n = 377). Overall, the incidence rates of composite outcomes, death, SSE, major bleeding, and heart failure were 8.69, 4.21, 1.51, 2.27, and 2.84 per 100 person-years, respectively. When compared to LCA class 1, hazard ratios (HR) of composite outcome of LCA classes 3 and 2 were 3.86 (3.06-4.86) and 2.31 (1.91-2.79), respectively. ABC pathway compliance was associated with better outcomes in LCA classes 2 and 3 with the HR of 0.63 (0.51-0.76) and 0.57 (0.39-0.84), but not in LCA class 1.LCA can identify patients who are at risk of developing adverse clinical outcomes. The implementation of holistic management based on the ABC pathway was associated with a reduction in the composite outcomes as well as the individual outcomes.

Atrial fibrillation (AF) is prevalent in dialysis-dependent patients, who face higher risks of thromboembolism and bleeding. Although vitamin K antagonists (VKAs) are commonly used for anticoagulation, the benefits of factor Xa (FXa) inhibitors over VKAs in this population are unclear. This systematic review aims to compare the efficacy and safety of VKAs and FXa inhibitors based on randomized controlled trials (RCTs). We conducted a systematic search of PubMed and Embase for RCTs comparing FXa inhibitors and VKAs up to November 2024. The primary safety outcome was major bleeding, and the primary efficacy outcome was stroke or systemic embolism (SSE). Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. This meta-analysis included 486 dialysis-dependent AF patients from 4 RCTs, with a median follow-up of 26 weeks to 1.88 years. FXa inhibitors were associated with a reduced risk of major bleeding compared to VKAs (RR = 0.64, 95% CI = 0.42-0.99; p = 0.04), but no significant difference in SSE (RR = 0.46, 95% CI = 0.20-1.02; p = 0.06). FXa inhibitors also showed a significantly lower risk of intracranial bleeding (RR = 0.40, 95% CI = 0.17-0.96; p = 0.04), but no differences in other outcomes, including gastrointestinal bleeding, hemorrhagic stroke, ischemic stroke, acute coronary syndrome, and mortality. This systematic review and meta-analysis suggest that FXa inhibitors may offer a safer alternative to VKAs for AF patients on dialysis, with a lower risk of bleeding and similar risks of stroke and mortality.

Inherited deficiency of the antithrombin (hereditary antithrombin deficiency, AT deficiency, OMIM #613118) is a relatively rare (1:2,000-3,000) autosomal-dominant disorder with high risk of venous thromboembolism. The molecular basis of this condition has not yet fully understood, highlighting the need for further research to elucidate the underlying pathological mechanisms.This study aimed to investigate coagulation parameters and genetic phenotypes in a proband with hereditary antithrombin deficiency and her family members. Additionally, the investigation sought to provide preliminary insights for the molecular pathogenesis of this condition.Blood coagulation parameters, including plasma antithrombin activity (AT:A), antithrombin antigen (AT:Ag), protein C activity (PC:A), and protein S activity (PS:A) were measured in the peripheral blood of each family member by a Stago instrument. Peripheral blood was also extracted and sequenced to identify possible genetic mutation sites. The functional impact of variants on protein was subsequently analyzed by bioinformatics software.The proband, her mother, and brother all exhibited decreased activity and antigen of AT but normal PC and PS activity. The proband's father had normal activity and antigen levels of AT, PC, and PS. Sequencing revealed the proband's mother inherited the SERPINC1:c.661T > C,p.(Trp221Arg) heterozygous variant and her father harbored PROC:c.572_574del,p.(Lys193del) heterozygous variant while the proband as well as her brother carried both. Conservation analysis revealed that Trp221 is highly conserved across homologous species. Bioinformatics tools consistently classify the p.Trp221Arg mutation as "pathogenic" or "deleterious." Protein modeling indicated that the p.Trp221Arg variant does not alter the protein structure but may modify glycosylation sites to affect its function.The proband and family members exhibited varying degrees of decreased levels of AT and thrombosis, which were closely associated with inheritance of SERPINC1:c.661T > C,p.(Trp221Arg).

Various reactions are involved in the phases of activation and further propagation of coagulation in space. The effects of different anticoagulants on these phases are unknown. Our aim was to study how different anticoagulants affect the activation and propagation phases of coagulation.Coagulation in the presence of low-molecular-weight heparin (nadroparin), and direct oral thrombin or factor Xa inhibitors (dabigatran and rivaroxaban, respectively) was studied in vitro and ex vivo via a global blood coagulation assay (Thrombodynamics-4D), which allows simultaneous analysis of thrombin activity in space and the clot growth rate. The ex vivo measurements were carried out in dynamics (8-9 days). The presence of asymptomatic thrombosis after 7 to 8 days of treatment was determined for each group of patients via ultrasound of the lower extremities.All the tested anticoagulants inhibited thrombin generation but resulted in different patterns of thrombin spatial distribution and clot growth. The reversible inhibitors-dabigatran and rivaroxaban-inhibited the initiation phase of coagulation, while further clot growth was altered moderately. Irreversible nadroparin weakly affected the initiation phase of thrombin generation, but unlike dabigatran and rivaroxaban, it could completely suppress spatial thrombin propagation. Asymptomatic thrombosis was observed in 0%, 11%, and 29% of the patients in the nadroparin, dabigatran, and rivaroxaban groups, respectively.Antithrombin-dependent and independent inhibitors act differently on different phases of coagulation. High concentrations of dabigatran or rivaroxaban are insufficient to completely prevent fibrin clot growth, but even small amounts of heparin completely suppress this growth, due to factor IXa inhibition.

Compared with an arterial thrombus (AT) or a venous thrombus (VT), there is limited knowledge about arteriovenous thrombus (AVT). AVT develops in 69% of arteriovenous fistulae (AVF) and 50% of arteriovenous grafts (AVG) within 1 year. Thrombosis remains one of the major complications after creation of a vascular access often resulting in failure of the access.To characterize and differentiate AVT from VT or AT.An AVT model was established by a needle puncture through the aorta to the inferior vena cava (IVC) in wild type mice and different reporter mice and compared with a mouse venous thrombus (VT) model using IVC ligation. AVT was also examined under defined arteriovenous flow conditions. AVT was examined by gross view, histology, immunofluorescence, and scanning electron microscopy.AVT occurs immediately at the juxta-anastomotic area (JAA) after successful arteriovenous flow was established, with platelets being a major component of early AVT. Reduced injury to the endothelium resulted in smaller AVT, whereas local delivery of rapamycin to inhibit cell proliferation failed to decrease the volume of the AVT. Incomplete reendothelialization of the peri-fistula exit area correlated with growth of the AVT. AVT universally presents at the JAA in other arteriovenous models.We provide the first detailed histopathological characterization of AVT induced by AVF. AVT originates from the injured vessel wall and is more similar to AT than VT. This model provides a valuable tool to characterize AVT. Both this AVT model and our data have potential for clinical translation.