Thrombosis and haemostasis最新文献

Background:  Asthma is associated with a prothrombotic state. Plasma factor VIIa-antithrombin complex (FVIIa-AT) concentrations indirectly reflect the interaction of tissue factor (TF) with FVII. Since TF is a key initiator of coagulation in vivo, we hypothesized that FVIIa-AT concentrations are higher in asthma.

Methods:  In 159 clinically stable adult asthma patients and 62 controls, we determined FVIIa-AT in plasma and analyzed their relation to circulating inflammatory and prothrombotic markers together with the total plasma potential for fibrinolysis (clot lysis time, CLT) and thrombin generation. We recorded clinical outcomes, including asthma exacerbations, during 3-year follow-up.

Results:  Asthma patients were characterized by 38.5% higher FVIIa-AT (p < 0.001), related to bronchial obstruction (FEV₁: r = -0.397, p < 0.001), asthma severity (r = 0.221, p = 0.005), and duration (r = 0.194, p = 0.015) compared to controls. FVIIa-AT showed weak positive associations with C-reactive protein (r = 0.208, p = 0.009), fibrinogen (r = 0.215, p = 0.007), and CLT (r = 0.303, p < 0.001) but not with thrombin generation parameters. In the follow-up (data obtained from 151 patients), we documented 151 severe asthma exacerbations in 51 (33.8%) patients, including 33 (21.9%) with ≥2 such events. Exacerbation-prone asthma phenotype was related to 13.1% higher FVIIa-AT (p = 0.012), along with asthma severity and control (p < 0.003, both). High FVIIa-AT (that is ≥100.1 pmol/L), defined on receiver operating characteristic curves, was linked to exacerbation-prone asthma phenotype (odds ratio 1.85; 95%CI: 1.23-2.80, p = 0.003) and shorter time to first exacerbation (p = 0.023).

Conclusion:  This study is the first to show that FVIIa-AT concentrations are higher in asthma in relation to its severity and may help identify individuals at risk of the exacerbation-prone asthma phenotype.

Objective:  To investigate the classification, clinical manifestations, laboratory findings, and genetic mutations associated with hereditary fibrinogen disorders in Chinese population.

Methods:  Between February 2015 and February 2022, 65 patients with congenital fibrinogen disorders (CFD) were identified at Wuhan Union Hospital. Comprehensive data were available for 51 patients, allowing for a retrospective analysis.

Results:  The cohort comprised 17 males (33.3%) and 34 females (66.7%), with a median diagnosis age of 35.0 years (interquartile range: 25.5-42.5). Of the patients, 35 (68.6%) were diagnosed with dysfibrinogenemia, 8 (15.7%) with hypofibrinogenemia, 7 (13.7%) with hypodysfibrinogenemia, and 1 (2.0%) with afibrinogenemia. The median diagnosis ages for the asymptomatic, Grade 1, Grade 2, and Grade 3 groups were 44.5 years (range: 37-58.5), 28 years (22.5-36.5), 35.5 years (21.75-41), and 28 years (22.75-30.75), respectively. The asymptomatic group had the latest diagnosis age, whereas Grade 3 had the earliest. A negative correlation was observed between Fg:C levels and bleeding severity (rs = - 0.2937, p = 0.0365). In total, 52 variants were found in 51 unrelated patients, with one patient carrying two mutations. The 37 distinct mutations included 11 in FGA, 3 in FGB, and 23 in FGG.

Conclusion:  This study investigates the clinical, laboratory, and genetic characteristics of patients with CFD in China, revealing a negative correlation between Fg:C levels and bleeding severity. Female patients are at higher risk for gynecological complications due to physiological traits. Additionally, R35 in FGA and R301 in FGG were identified as hotspot mutations.

Background:  Thrombocytopenia is one of the most common manifestations of the antiphospholipid syndrome (APS). However, its causes are still poorly defined. We have shown recently that antiphospholipid antibodies (aPL) directed against β2-glycoprotein I (β2GPI) of the IgG isotype induced platelet activation and aggregation while aPL directed against cardiolipin and anti-β2GPI IgM had no effect. Since platelet activation by anti-β2GPI might lead to platelet consumption and lower platelet count or overt thrombocytopenia, we analyzed the association of aPL with platelet count.

Material and methods:  Data of consecutive patients with test orders for anticardiolipin IgG/IgM and anti-β2GPI IgG/IgM and full blood count in our laboratory from August 2015 to April 2019 were analyzed.

Results:  We identified 2,815 individual patients (mean age 45.7 years; 71.1% women) with complete data on aPL and platelet count, of which 445 individuals (mean age 41.0 years; 75.3% women) showed increased aPL titers. Patients with anti-β2GPI of the IgG isotype had significantly lower platelet count (220 ± 84 versus 264 ± 90 G/L, p < 0.0001) and higher frequency of thrombocytopenia (platelet count <100 G/L; 12.2% versus 2.4%, p < 0.005) than patients negative for all four aPL. These differences could not be explained by comorbidities or medications. Neither anticardiolipin IgG nor aPL of the IgM isotype was associated with lower platelet count or thrombocytopenia.

Conclusion:  The exclusive association of anti-β2GPI IgG aPL with low platelet count coincides with its unique ability to activate platelets and induce aggregation in vitro. This supports the hypothesis that anti-β2GPI IgG aPL may induce thrombocytopenia by chronic platelet consumption in vivo.

.VTE-WEAK study provides valuable insights into the complex interaction between psychosocial and clinical factors in VTE recurrence. This stud reinforces the necessity of a holistic approach to VTE management, combining psychosocial evaluation with targeted interventions alongside traditional clinical strategies.

Background:  Studies found an association between anemia and overall mortality and major bleeding (MB) in patients with acute venous thromboembolism (VTE), but whether anemia is causally related to death, bleeding, or recurrent VTE is uncertain.

Objectives:  To explore the association between anemia at baseline and short-/long-term clinical outcomes in a prospective cohort of 928 patients with acute VTE.

Methods:  We defined anemia as a hemoglobin <13 g/dL for men/< 12 g/dL for women. The primary outcome was overall mortality, secondary outcomes were MB and recurrent VTE at 3 months (short term) and over the entire follow-up (long term). An independent committee determined the cause of death. We examined the association between anemia and clinical outcomes using multivariable regression, adjusting for confounders, periods of anticoagulation, and the competing risk of death if appropriate.

Results:  Overall, 42% of patients had anemia. After a median follow-up of 30 months, 21.4% died, 13.8% experienced MB, and 12.4% had recurrent VTE. Anemia was associated with long-term overall mortality (adjusted HR 1.46, 95%CI 1.06-2.02) but not with short-term mortality, MB, or recurrent VTE. Per 1 g/dL increase in hemoglobin, long-term mortality risk decreased by 8%. Anemic patients were more likely to die from left ventricular failure than non-anemic patients (9.8% versus 1.3%).

Conclusion:  Anemic patients with VTE carried a higher long-term mortality risk than those without anemia, possibly due to an excess in mortality from left ventricular failure. The lack of an independent relationship between anemia and bleeding indicated that anemia might have confounding rather than causal effects.

Background - Although Factor XI (FXI) inhibitors are currently tested for the prevention of thrombotic events, their early treatment could prevent thrombus consolidation in ST-segment elevation myocardial infarction (STEMI). This study aims to characterize coagulation FXI levels and their variations in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Methods - Patients with STEMI were prospectively enrolled between December 2023 and May 2024. FXI activity (FXIa) levels were measured at admission and after PCI (i.e., before discharge). Variations in FXIa levels were evaluated. Differences in indicators of thrombotic risk between groups with high and low FXIa variability were analyzed, and predictors of high FXIa variability were identified. Results - After screening, 54 patients with STEMI were included. The median FXIa level was 0.865 IU/mL (interquartile range [IQR] 0.554-0.978) at admission and 1.161 IU/mL (IQR 0.982-1.317) before discharge, with a median difference of +34.2% (p-value < 0.001). No significant differences were found in indicators of thrombotic risk between groups at high and low FXIa variability, except for the days intercurred between the essays (p-value = 0.016). Neither this nor other variables emerged as independent predictors of high FXIa variability. Conclusions - This study firstly reported an increase in FXIa levels from admission to discharge in STEMI patients undergoing PCI. Common indicators of thrombotic risk were not associated with FXIa levels or their variability. These findings aim to stimulate further research into anticoagulant therapies tailored to the patient's coagulative state and disease.

Background: Data on risks and benefits of long-term anticoagulants in patients with a life-limiting disease are limited. This cohort study aims to describe (dis)continuation of anticoagulants and incidences of bleeding and thromboembolic events in vitamin K antagonist (VKA) users with a life-limiting disease.

Methods: Data from five Dutch anticoagulation clinics were linked to data from Statistics Netherlands and the Netherlands Cancer registry. Prevalent VKA users diagnosed with a pre-specified life-limiting disease between 01/01/2013 and 31/12/2019 were included and followed until 31/12/2019. Hospitalization data were used to identify bleeding and thromboembolic events. Cumulative incidences of anticoagulant discontinuation were calculated, accounting for death as competing risk, and event rates were determined for both anticoagulant exposed and unexposed person-years (PYs).

Results: Among 18,145 VKA users (median age 81 years, 49% females, median survival time 2.03 years), the most common life-limiting diseases were heart disease (60.0%), hip fracture (18.1%), and cancer (13.5%). One year after diagnosis, the cumulative incidence of anticoagulant discontinuation was 14.0% (95%CI: 13.5-14.6). Over 80% of patients continued anticoagulant therapy until the last month before death, with median 14 days between discontinuation and death. Event rates per 100 PYs (95%CI) were comparable during anticoagulant use and after discontinuation for bleeding 2.6 (2.4-2.8) versus 2.1 (1.5-2.8); venous thromboembolism 0.2 (0.1-0.2) versus 0.4 (0.2-0.7); and arterial thromboembolism 3.1 (2.9-3.3) versus 3.3 (2.6-4.2).

Conclusion: Most VKA users with a life-limiting disease continued anticoagulant treatment during their last phase of life, with similar rates of bleeding and thromboembolic events during use and after discontinuation.