TH open : companion journal to thrombosis and haemostasis最新文献

Background: Although the association between platelet characteristics and the risk of developing atherosclerosis (AS) has been acknowledged, the specific role of platelets in AS development and progression remains unclear. Therefore, the aim of this study was to identify platelet characteristics in patients with and without AS to enhance the understanding of their pathophysiological functions and discover more sensitive biomarkers for AS diagnosis.

Methods: We conducted a cross-sectional study involving AS patients and healthy controls (N). Based on the Chinese guidelines for diagnosing carotid and vertebral artery AS and the 2010 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines, we defined AS using carotid ultrasound to measure intima-media thickness (IMT). General information, including sex, age, height, and weight, was collected upon enrollment. A series of examinations, including physical exams, serum lipid profiles, blood glucose tests, liver and kidney function tests, platelet aggregation assays, and carotid artery ultrasounds, was performed. Platelets were extracted from plasma for RNA-seq analysis.

Results: No statistically significant differences in age, sex, body mass index, or blood pressure were observed between the groups. Total triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, red blood cell count, hemoglobin concentration, cholesterol levels, and carotid IMT were significantly greater, and vascular endothelial function was significantly lower in the AS group than in the N group. Using RNA-seq, we identified 784 differentially expressed genes-141 downregulated and 643 upregulated-with Gene Ontology enrichment showing significant associations with blood coagulation pathways, among others. Weighted correlation network analysis revealed four hub genes related to IMT: Integrin Subunit Alpha 2b (ITGA2B), Transforming Growth Factor Beta 1 (TGFB1), Platelet Factor 4 (PF4) , and Glycoprotein IX Platelet (GP9) .

Conclusion: Our findings indicate moderate correlations of elevated ITGA2B ( r  = 0.327, p  = 0.004), TGFB1 ( r  = 0.362, p  = 0.001), PF4 ( r  = 0.240, p  = 0.038), and GP9 ( r  = 0.302, p  = 0.008) levels with increased IMT, suggesting that these genes may serve as predictive biomarkers for AS.

Background: Recurrent thrombosis poses a clinical challenge in patients with antiphospholipid syndrome (APS). There are limited data on risk factors due to its rarity.

Aims: This study aimed to study the association between cardiovascular (CV) and APS-related risk factors and recurrent thrombosis and evaluate the adjusted Global Anti-Phospholipid Syndrome Score (aGAPSS).

Methods: This retrospective cohort study comprised APS patients at Karolinska University Hospital, Sweden, from 2014 to 2020 with follow-up until the last medical visit or death. Multiple thrombotic events per patient were included. Cox proportional hazard model estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Logistic regression and Poisson regression were conducted to further examine the relation between risk factors and recurrent thrombosis.

Results: The cohort included 250 patients (67% women and 52% primary APS) with a median age of 44.5 (35-59) years. Forty-nine recurrent thrombotic events occurred in 36 patients, yielding an incidence of 4.46 (95% CI 3.30-5.90) per 100 person-years. Thrombocytopenia was associated with recurrent thrombosis (HR 2.57 [95% CI 1.01-6.02]). Although CV risk factors were not consistently significant for recurrent thrombosis, chronic kidney disease (CKD) indicated an increased probability (OR 2.55 [95% CI 1.01-6.26]). For each point of aGAPSS, the HR for recurrent thrombosis increased by 10% (1.10 [95% CI 1.01-1.19]). Notably, inadequate anticoagulation triggered recurrence in almost a quarter of cases.

Conclusion: Thrombocytopenia was confirmed as a major risk factor for recurrent thrombosis. CKD warrants closer attention in future assessment. Although an increase in aGAPSS was associated with recurrent thrombosis, further evaluation is required. Improving anticoagulation treatment is essential to reduce recurrence.

[This corrects the article DOI: 10.1055/s-0041-1736037.].

Background: Approximately 20% of patients with cancer will have cancer-associated venous thromboembolism (CAT), which is associated with significant morbidity and mortality. Despite its clinical importance, CAT awareness in cancer patients and caregivers remains low. We sought to assess the patients' knowledge of CAT through a national survey.

Materials and methods: A survey assessing knowledge of different aspects of CAT was developed by a steering committee including four clinicians with expertise in CAT and a patient partner with lived experience. Survey dissemination among patients with cancer occurred through the Environics network, the Thrombosis Canada member network, the Thrombosis Canada social media platforms, and was advertised through Instagram and Facebook, and the Canadian Cancer Survivor Network newsletter.

Results: Out of the 312 patients with cancer or survivors who responded to the survey, 179 (57.4%) were female, and 118 (37.8%) were over 65 years old. Overall, 119 patients (38.1%, 95% confidence interval [CI]: 37.7-49.8%) reported having no knowledge of CAT. Only 84 (26.9%, 95% CI: 22.1-32.2%) and 94 (30.1%, 95% CI: 25.1-35.6%) patients reported receiving education about their underlying risk of CAT or education about signs and symptoms of venous thromboembolism, respectively. A total of 66 (21%, 95% CI: 16.8-26.1%) patients reported being informed by a health care professional about considering thromboprophylaxis. Patients were interested in learning more about the risk of CAT, its associated risk factors, and the benefits and potential side effects of thromboprophylaxis.

Conclusion: Many patients with cancer lack awareness or knowledge of CAT. Our results highlight ongoing education and awareness of the CAT burden.

Direct oral anticoagulants such as edoxaban are standard of care in current treatment of venous thromboembolism (VTE). However, phase III trial data need confirmation in real-world settings. We extracted data from the prospective, noninterventional multiple-indication DRESDEN NOAC REGISTRY to evaluate outcome rates during VTE treatment with edoxaban. Patients were included in this analysis, if they had acute VTE and if patient enrolment and edoxaban initiation occurred within 30 days after VTE diagnosis. Patient characteristics, treatment persistence, and clinical outcomes were centrally adjudicated using standard definitions. Until December 31, 2023, 323 acute VTE patients (median age 67 years, 56.7% male) were enrolled and initiated edoxaban within 7.8 ± 4.9 days (mean) for isolated deep vein thrombosis (DVT) (57.6%) or pulmonary embolism (PE) ± DVT (42.4%). Mean duration of follow-up was 3.9 ± 1.9 years with a mean duration of edoxaban exposure of 1.5 ± 1.7 years. During ongoing edoxaban therapy, 3/323 patients (0.9%) experienced recurrent VTE (0.6/100 patient-years); 141/323 (43.7%) patients reported clinically relevant International Society on Thrombosis and Haemostasis (ISTH) nonmajor bleeding and 16 reported ISTH major bleeding (5.0%; 3.2/100 patient-years). Death was observed in 53 patients (4.1/100 patient-years). At 6 months, 78.2% were still taking edoxaban, 2% were electively switched to dose-reduced secondary prophylaxis with apixaban 2.5 mg twice a day or rivaroxaban 10 mg once daily. The remaining patients had a scheduled end of VTE treatment (11.4%) or were switched to nonedoxaban therapeutic anticoagulation (6.2%). Our results indicate effectiveness of edoxaban in acute VTE treatment with excellent persistence in the treatment and low rates of unplanned discontinuation. Bleeding was frequently observed, but rates of major bleeding were low and comparable to phase III data.

Objective: This study reviewed the management and outcomes of traumatic brain injury (TBI) patients who developed venous thromboembolism (VTE) during hospitalization, focusing on the timing of VTE diagnosis and anticoagulation initiation.

Methods: This retrospective, single-center study utilized data from the University of Texas Trauma Database. Patients were categorized based on VTE diagnosis timing (early ≤7 days, late >7 days). The primary outcome was in-hospital mortality. Secondary outcomes included mortality specifically among patients who were receiving anticoagulation treatment, hemorrhagic complications, predictors associated with early anticoagulation initiation (defined as ≤ 7 days from VTE diagnosis), and whether anticoagulation timing influenced mortality.

Results: Among 237 patients (early: 145, late: 92), the mean age was 59 ± 20 years vs. 55 ± 20 years ( p  = 0.133). Males comprised 68% vs. 78% ( p  = 0.038). Subdural hematomas were the predominant injury (63% vs. 68%, p  = 0.443). In-hospital mortality was similar (10% vs. 13%, p  = 0.524) and did not differ between anticoagulated and non-anticoagulated patients ( p  = 0.94). Among patients who died, 73% in the early group and 100% in the late group had received anticoagulation ( p  = 0.053). Hemorrhage expansion was more frequent in early VTE patients (40% vs. 0%, p  = 0.046). Pulmonary embolism was associated with early anticoagulation (OR = 1.86, 95% CI: 1.09-3.17, p  = 0.023), while severe neurologic injury (GCS <9) reduced its likelihood (OR = 0.53, 95% CI: 0.28-0.98, p  = 0.042).

Conclusion: In-hospital mortality did not differ by VTE timing or anticoagulation status. However, hemorrhage expansion was more frequent in early VTE patients, particularly those with subdural hematomas, emphasizing the need for individualized anticoagulation strategies.

Objective: To assess real-world treatment patterns and outcomes in previously treated patients ≥12 years old with severe haemophilia A treated with marketed factor VIII (FVIII) replacement products.

Methods: Data were collected prospectively between 25 January 2019 and 30 November 2020 across 45 sites in 17 countries. Primary endpoint was annualized bleed rate (ABR). Secondary endpoints included factor consumption, bleed treatment, joint health, and safety. Exploratory endpoints included pain and quality of life outcomes.

Results: A total of 157 patients received ≥1 FVIII injection (prophylaxis n  = 139, on-demand n  = 19). Mean (standard deviation; SD) observation period was 43.1 (13.3) weeks. Median (quarter [Q]1, Q3) ABR was 2.0 (0.0, 5.7) for those on prophylaxis. Those receiving standard half-life FVIII products or extended half-life FVIII products had a median (IQR) ABR of 2.2 (0.0, 6.1) and 1.3 (0.0, 5.0), respectively. Still, only 35% of patients on prophylaxis experienced zero bleeds and 18% had five or more bleeds in a year. Approximately 23% of bleeding episodes required >1 FVIII dose for resolution. The mean (SD) number of routine prophylaxis injections/week was 2.2 (1.1). Median (Q1, Q3) annualized factor consumption for patients on prophylaxis was 4,106.4 (3,151.6, 5,291.2) IU/kg/year. No changes in Haemophilia Joint Health Score (mean [SD] of 16.1 [19.3] versus 15.7 [17.7]), PROMIS pain intensity 3a T-score (mean [SD] 41.6 [8.2] versus 40.9 [9.1]), or Haem-A-QoL (mean [SD] 30.6 [17.3] versus 29.5 [17.4]) were observed between baseline and the end of the observation period for those using prophylaxis.

Conclusions: Prophylaxis using standard or extended half-life FVIII replacement therapies achieves adequate haemostatic control in only about half of patients, with some experiencing very poor outcomes. Real-world data highlight the urgent need to optimize prophylaxis to enhance haemostatic control, ideally achieving a zero ABR and its associated benefits.

The development of inhibitors to von Willebrand factor (VWF) is a rare but potentially serious complication of VWF replacement therapy in patients with von Willebrand disease (VWD). Patients who develop VWF inhibitors may become unresponsive and/or may develop severe anaphylactic reactions to VWF concentrates. Data on inhibitor development and management in VWD remain limited, and better understanding of inhibitor development is an important goal in VWD management. The WIL-31 study demonstrated the efficacy and safety of prophylaxis with wilate, a plasma-derived VWF/factor VIII (pdVWF/FVIII) concentrate, in children and adults with VWD of all types. The annualized bleeding rate (ABR) was reduced by 84% with wilate prophylaxis compared with on-demand treatment, and prophylaxis was well tolerated. No inhibitors developed during the WIL-31 study. Here, we report two brothers with type 3 VWD who at the 6-month visit were found to have VWF inhibitors, which on further investigation were found to have already been present before the study. Despite the presence of inhibitors, neither patient showed any clinical symptoms, and prophylaxis with wilate led to a ≥85% reduction in ABR in both boys compared with on-demand treatment.

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone encoded by the SERPINH1 gene, has emerged as a groundbreaking focus in thrombosis research. Recent findings published in "Science" have revolutionized our understanding of thrombosis, identifying HSP47 as a critical mediator in a new thrombosis target for treatment. This discovery not only unveils a novel pathway in thrombosis but also opens new avenues for therapeutic intervention. HSP47's significance extends beyond thrombosis, influencing pathological processes such as fibrosis and cancer. In fibrosis, its upregulation promotes collagen deposition, while its dysregulation in osteogenesis imperfecta (OI) Type X underscores the protein's indispensable role in collagen biosynthesis. The therapeutic challenge lies in balancing HSP47 inhibition to reduce fibrotic burden without impairing its essential physiological functions. In cancer, HSP47 plays dual roles. It supports tumor progression through collagen stabilization and metastasis facilitation while contributing to tissue repair under hyperthermia treatment combined with radiotherapy or chemotherapy. However, its overexpression can exacerbate tumor aggressiveness via mechanisms such as angiogenesis and epithelial-mesenchymal transition. This review emphasizes the pivotal discovery of HSP47's thrombogenic role and its broader implications in disease biology. These findings mark a paradigm shift in thrombosis research and underscore the potential of HSP47 as a target in diverse pathological contexts, from platelet-driven diseases to fibrotic and oncological disorders.