Research and Practice in Thrombosis and Haemostasis最新文献

Background: Health literacy can influence self-management, leading to improved health outcomes in pediatric patients with venous thrombotic events (VTEs).

Objectives: To assess general health literacy in adolescents and parents/caregivers of children diagnosed with VTE, and their perception and satisfaction with overall thrombosis-related knowledge, thrombosis knowledge compared to that of other conditions, and beliefs regarding thrombosis knowledge importance.

Methods: Patients aged 10 to 18 years with VTE history and parents/caregivers of patients aged 0 to 18 years with VTE attending clinic were recruited in this cross-sectional study. Health literacy was measured using the Rapid Estimate of Literacy in Medicine Short Forms (Adolescent and Adult), the Health Literacy Assessment Scale for Adolescents, and the e-Health Literacy Scale. Self-reported perception, satisfaction, comparative knowledge, and beliefs regarding thrombosis knowledge were assessed using researcher-generated questions.

Results: In total, 101 participants (50 adolescents, 51 parents/caregivers) were recruited at a median of 27 months (25th-75th percentile; 12-62 months) post-VTE diagnosis. Overall, 74% of adolescents and 59% of parents/caregivers had ≥1 measure indicating low general health literacy. Only half the participants thought their thrombosis knowledge was similar to that of other diseases. Satisfaction with thrombosis-related knowledge was 44%; 96% agreed that learning about thrombosis was important. Adolescents reported higher satisfaction with their knowledge than parents/caregivers, but satisfaction was not associated with demonstrated thrombosis knowledge.

Conclusion: Most participants had low general health literacy levels, and more than half were not satisfied with their thrombosis-related knowledge. Adolescents tended to overestimate their knowledge. Effective strategies to support health literacy in this population are needed.

Background: Cancer-associated thrombosis (CAT) is a leading cause of death in patients diagnosed with cancer. However, pharmacologic thromboprophylaxis use in cancer patients must be carefully evaluated due to a 2-fold increased risk of experiencing a major bleeding event within this population. The electronic health record CAT (EHR-CAT) risk assessment model (RAM) was recently developed, and reports improved performance over the widely used Khorana score. Extensive RAM external validation is crucial to determine accuracy across diverse patient populations prior to clinical utilization.

Objectives: To externally validate EHR-CAT using data from 2103 patients with cancer at the Boston Medical Center (BMC), New England's largest safety-net hospital, and to compare this RAM with the Khorana score.

Methods: We conducted a retrospective study of BMC cancer patients diagnosed between January 2014 and December 2022 using data from the BMC tumor registry and EHR system. We validated the RAM using measures of discrimination and calibration.

Results: The EHR-CAT score exhibited a strong ability to discriminate the risk of CAT (C statistic, 0.67), which was substantially higher than the classic Khorana score (C statistic, 0.58). This increased discrimination power reflects the 20% of patients that were reclassified into high or low risk by the expanded score. Model calibration was also strong in this dataset.

Conclusion: In our external validation, the recently published EHR-CAT score showed clear and improved separation of patients at high and low risk for CAT. The utilization of this expanded CAT score could facilitate improved targeting of at-risk cancer patients for prophylactic therapy.

The question of whether scuba diving is safe for patients with a history of venous thromboembolism (VTE) remains unanswered. Cases of VTE have been reported after decompression accidents but not following properly conducted dives. However, the risk of VTE and bleeding on anticoagulant therapy during diving has yet to be defined. Medical diving societies make different recommendations regarding the risk of scuba diving in patients with a history of VTE and/or hereditary thrombophilia and regarding the bleeding risk under anticoagulation associated with dives. There is no epidemiologic or pathophysiologic evidence described in the literature to support a direct association between VTE and diving. Therefore, VTE cannot be considered as a definite contraindication for scuba diving. Further studies are needed to conclusively establish the risk of VTE associated with diving and to guide the development of medical guidelines by diving societies.

Background: The Vienna Prediction Model (VPM) identifies patients with a first unprovoked deep vein thrombosis of the leg and/or pulmonary embolism who have a low recurrence risk and may, therefore, not benefit from extended-phase anticoagulation.

Objectives: The aim of this study was to evaluate patients with a predicted high risk of recurrent venous thromboembolism (VTE).

Methods and results: We prospectively followed 266 patients in whom the VPM had predicted a recurrence risk of more than 5.5% at 1 year for a median of 13.5 months. Their median age was 56 years, and 96% were men. After the VPM risk assessment, 196 patients restarted anticoagulation. While on anticoagulation, none of the patients experienced recurrent VTE, whereas 4 patients had nonmajor clinically relevant bleeding (absolute bleeding rate, 1.8 [95% CI, 0.5-4.5] events per 100 patient-years). Seventy patients were left untreated after VPM risk assessment for various reasons. Among patients not using anticoagulation, 15 had recurrence (absolute recurrence rate, 18.1 [95% CI, 10.1, 29.9] events per 100 person-years). According to the extended Kaplan-Meier analysis, the probability of VTE recurrence in patients not on anticoagulation was 10.1% and 17.9% at 6 and 12 months after VPM risk assessment, respectively.

Conclusion: Anticoagulant therapy is effective and safe in patients with an unprovoked VTE, in whom the VPM had predicted a high risk of recurrent VTE. If these patients are left untreated, the risk of recurrence is high.

Background: Pulmonary embolism (PE) is a life-threatening condition with high morbidity and mortality. The diagnosis of PE is challenging due to nonspecific symptoms, making reliable diagnostic tools essential. This study addresses the clinical impact of interassay variability in D-dimer measurements on the utilization and diagnostic yield of computed tomography pulmonary angiography (CTPA).

Objectives: To investigate the effect of different D-dimer assays on the decision to perform CTPA and the subsequent diagnostic yield in patients with suspected PE.

Methods: This retrospective, multicenter cohort study analyzed data from 3 teaching hospitals in the southwest region of the Netherlands, covering the years 2018, 2019, 2022, and 2023. The study included data from 40,096 clinically requested D-dimer results and 11,372 CTPA records of patients with suspected PE. The D-dimer assays used were the Roche Tina-quant and Siemens INNOVANCE.

Results: The study found significant differences in CTPA utilization and diagnostic yield based on the D-dimer assay used. In 2018 to 2019, hospitals using the Roche Tina-quant assay ordered 21% fewer CTPA scans and had a 9% higher positivity rate compared with those using the Siemens INNOVANCE assay.

Conclusion: The findings highlight the necessity for assay-specific cutoff values or, ideally, the standardization of the D-dimer assay to optimize the accuracy and efficiency of PE diagnosis. This study demonstrates that the choice of D-dimer assay significantly influences the clinical management of suspected PE, affecting both the number of CTPA scans performed and the positivity rate of these scans. Implementing assay-specific cutoff values or standardization of the D-dimer assay could reduce unnecessary CTPA scans, minimize patient exposure to radiation, and lower healthcare costs. These results advocate enhanced collaboration between clinicians and laboratory specialists to accurately interpret D-dimer results within the context of the specific assay used. Future research should validate these findings in prospective studies and explore standardized protocols that account for interassay variability.

Background: Abdominal aortic aneurysm (AAA) is characterized by the proteolytic breakdown of the extracellular matrix, leading to dilatation of the aorta and increased risk of rupture. Biomarkers that can predict major adverse aortic events (MAAEs) are needed to risk stratify patients for more rigorous medical treatment and potential earlier surgical intervention.

Objectives: The primary objective was to identify the association between baseline levels of these biomarkers and MAAEs over a period of 5 years.

Methods: Baseline levels of 3 proteases (matrix metalloproteinases 7, 8, and 10) and 3 protease inhibitors (tissue factor pathway inhibitor [TFPI], SerpinA12, SerpinB3) were investigated. Plasma levels of these biomarkers were quantified in 134 patients with AAA and 134 matched controls. Patients were followed for a 5-year period during which MAAEs were documented. The association between these markers and MAAEs was evaluated using Cox regression and Kaplan-Meier survival curves.

Results: TFPI was significantly elevated in patients with AAA and significantly associated with MAAE during the 5-year period (hazard ratio, 1.52; 95% CI, 1.15-2.01; P = .003) after adjusting for covariates. Kaplan-Meier survival analyses demonstrated that patients in the high TFPI group (defined as plasma levels >25.961 ng/mL) had significantly reduced freedom from the need for aortic repair and MAAEs.

Conclusion: These findings suggest that TFPI may serve as a valuable prognostic marker for the risk of MAAEs within 5 years in patients with AAA, potentially offering new tools for the medical management of patients with AAA.

Background: The development of acquired factor (F)V with inhibitor (AFVwI) is rare, resulting mainly in bleeding complications, although sporadic cases of thrombosis in adults have been reported.

Key clinical question: How do you diagnose and manage a pediatric case of acute deep venous thrombosis associated with the concurrent finding of AFVwI?

Clinical approach: A 13-year-old female with Crohn's Disease and May-Thurner anatomy developed extensive deep venous thrombosis of the left lower extremity, complicated by the finding of AFVwI, discovered during the evaluation of a prolonged prothrombin time and a low FV activity. Anticoagulation was initiated with low-molecular-weight heparin followed by a direct oral anticoagulant, rivaroxaban, without any complications. AFVwI was undetectable after 5 months with normalization of FV activity.

Conclusion: Our case highlights the first pediatric case of thrombosis with a rare finding of AFVwI, successfully managed with anticoagulation therapy with complete resolution.

Congenital hemophilia A (HA) disease severity has traditionally been categorized according to intrinsic factor (F)VIII levels, with <1% of normal indicating severe HA, 1% to 5% moderate HA, and 6% to 40% mild HA. However, mounting evidence illustrates considerable variability in bleeding phenotype regardless of FVIII level. Despite treatment advances, people with moderate or mild HA may be neglected, as treatment guidelines and established norms focus on FVIII levels, and many clinical trials do not include people with FVIII > 1%. Data from the HAVEN 6 trial demonstrated that people with moderate or mild HA, for whom prophylaxis was warranted by the treating physician's judgment, experienced a clear clinical benefit from receiving emicizumab prophylaxis. A shift in treatment paradigms to incorporate clinical phenotypes alongside FVIII levels should be encouraged. This change in practice would allow treaters to extend health equity to people with moderate or mild HA.

Background: Persons with hemophilia A are at risk of inhibitor development with repeated exposures to factor (F)VIII concentrates. When persons with nonsevere hemophilia A (NSHA) develop inhibitors, they are at risk of developing severe bleeding manifestations like persons with severe hemophilia A (SHA). Evidence to guide inhibitor eradication in this population is limited as opposed to persons with SHA who develop inhibitors. Hence, inhibitor eradication strategies in NSHA are based on observational and retrospective data and are largely adopted from evidence derived from SHA with inhibitors.

Key clinical question: Can immune tolerance induction be used for patients with NSHA who develop inhibitors?

Clinical approach: In this case series, we describe our single institutional experience with the management of 5 persons with NSHA who developed FVIII inhibitors, leading to significant bleeding complications, and underwent successful immune tolerance induction with eradication of FVIII inhibitor.

Conclusion: More research specific to persons with NSHA with inhibitors is warranted to develop guidelines regarding indications and strategies for inhibitor eradication therapy.

Background: Low-dose (LD) or intermediate-dose (MD) immune tolerance induction (ITI) is effective in children with severe hemophilia A (SHA) with high-titer inhibitors (HTIs) and is attractive in countries with economic constraints. However, high-quality evidence of their use is lacking.

Objectives: This was a multicenter randomized clinical trial comparing the efficacy, safety, and medication cost between LD-ITI and MD-ITI for SHA-HTI children.

Methods: Children with SHA aged <8 years with historical/pre-ITI inhibitor titer 5 to 200 Bethesda Units/mL in 3 centers were randomized 1:1 to receive LD-ITI (recombinant factor VIII [rFVIII] 50 IU/kg every other day) or MD-ITI (rFVIII 100 IU/kg/d) from January 2022 to June 2024 (ChiCTR2200056603, https://www.chictr.org.cn).

Results: Thirty-one patients (16 in MD-ITI and 15 in LD-ITI) were enrolled and followed for >24 months (median, 26.9; range, 24.0-29.5 months). The 2 groups had similar baseline clinical characteristics and similar success rates (93.8% [MD-ITI] vs 86.7% [LD-ITI]). Compared with LD-ITI, MD-ITI patients took a shorter median time to success (4.2 months vs 10.1 months) and partial success (2.7 months vs 6.6 months) and had lower mean rates for all bleeding (0.38/mo vs 1.40/mo) and joint bleeding (0.11/mo vs 0.83/mo). Between the 2 groups, although the MD-ITI group had higher rFVIII consumption (12,775 vs 7680 IU/kg), their total medication costs to success were similar (3626.49 vs 3240.38 US$/kg).

Conclusion: For SHA-HTI children, the success rate and cost for MD-ITI and LD-ITI regimens were similar. MD-ITI regimen would be a priority for regions with economic constraints, considering the shorter time to success, better bleeding control, and no increase in medication cost.