Research and Practice in Thrombosis and Haemostasis最新文献

Background: Emicizumab, a bispecific antibody that mimics factor (F)VIII, has significantly improved hemophilia A management. Although emicizumab levels can be measured, tools for estimating the hemostatic efficacy of emicizumab are lacking. Thrombin generation (TG) assays can distinguish bleeding phenotypes in persons with hemophilia A on FVIII prophylaxis and may also be used during emicizumab therapy.

Objectives: To assess the association between TG parameters, emicizumab levels, and bleeding in patients on emicizumab therapy.

Methods: A single-center longitudinal cohort study was conducted, with samples collected during the steady-state phase of emicizumab therapy. TG was measured using tissue factor (TF; TF-TG, 1 pM) and FXIa (FXIa-TG, 200 pM). Emicizumab concentrations were determined with mass spectrometry. Only treated bleeds were recorded. Pearson correlations (rho, r) were reported.

Results: Eighty-five samples from 49 patients were analyzed during a median of 1 year of emicizumab therapy. Most bleeds were traumatic (97%; n = 30), whereas 1 bleed was spontaneous. At 12 months, TF-TG (r = 0.42) showed a borderline correlation, and FXIa-TG (r = 0.15) showed no correlation with emicizumab concentrations. Although FXIa-TG showed a 9% higher endogenous thrombin potential in patients with zero vs ≥1 treated bleed (endogenous thrombin potential: 957 vs 878 nM/min, P = .045), neither the FXIa-peak height nor TF-TG showed any association with traumatic bleeding.

Conclusion: TG parameters showed no clinically relevant correlations with emicizumab plasma concentrations, were not associated with traumatic bleeding, and showed considerable intrapatient variability. Therefore, TG was not considered useful for monitoring coagulation potential in patients on steady-state emicizumab prophylaxis.

Background: The addition of caplacizumab to immune thrombotic thrombocytopenia (iTTP) treatment options has led to a renewed interest in characterizing the epidemiology and risk factors for bleeding in iTTP. Limited data exist on the bleeding risk in iTTP due to systemic underreporting in earlier cohorts.

Objectives: To describe the incidence, patterns, and predictors of bleeding in hospitalized iTTP patients independent of caplacizumab use.

Methods: We retrospectively analyzed the National Inpatient Sample database (2012-2019) and identified adult patients with a diagnosis of iTTP. Predictors of bleeding were determined by multivariable logistic regression analysis.

Results: We identified 3103 iTTP hospitalizations; bleeding occurred in 594 (19.1%), and 157 (5.1%) were characterized by major bleeding. Mucocutaneous bleeding (7.6%) was the most frequent type of bleeding and included heavy menstrual bleeding (2.6%), gingival (2.3%), epistaxis (1.4%), and skin/procedure-related bleeding (1.3%). This was followed closely by gastrointestinal bleeding (5.6%). Patients with bleeding were more likely to be Hispanic, have a weekend admission, and have a higher prevalence of comorbidities. In the multivariable analysis, Hispanic race (odds ratio [OR], 1.48; 1.14-1.91), Asian/Pacific Islander/Native American race (OR, 2.04; 1.51-2.76), coronary artery disease (OR, 1.70; 1.38-2.11), heart failure (OR, 1.39; 1.13-1.72), autoimmune disease (OR, 2.61; 2.08-3.26), Charlson Comorbidity Index ≥ 3 (OR, 2.08; 1.66-2.61), weekend admission (OR, 1.45; 1.22-1.72), and delay ≥2 days in plasma exchange initiation (OR, 1.63; 1.38-1.92), were significantly associated with major bleeding.

Conclusions: Bleeding is a relatively common issue in acute iTTP that has not been adequately addressed in existing literature. Further studies are needed to elucidate this risk and associated factors, especially given the incorporation of caplacizumab in the treatment of iTTP.

Background: Current guidelines recommend application of the 99th percentile to determine the cut-off value on at least 120 healthy donors regardless of sex for lupus anticoagulant (LA) ratio of each step. However, a statistically significant difference between the sexes has been found for LA ratio recently.

Objectives: To clarify whether this sex difference in dilute Russell's viper venom time (DRVVT) exists in various detection systems and the necessity of setting sex-specific cut-off values.

Methods: Blood samples from healthy donors were detected on 3 DRVVT detection systems, and the sex-specific cut-offs of DRVVT test were obtained based on the 99th or 97.5th centile of screen, confirm, and normalized ratios (NRs) grouped by sex in each system. One thousand one hundred twenty one female patients with suspected antiphospholipid syndrome (APS) were retrospectively investigated, the APS-associated clinical and laboratory characteristics of female patients stratified by different cut-offs of DRVVT ratio were compared.

Results: The DRVVT NRs of females were significantly lower than those of males on each system. The female patients with DRVVT NR between female-specific and regardless of sex cut-offs had higher positive rates of silica clotting time test and LA retest results after 12 weeks than those with DRVVT NRs lower than female-specific cut-off, there were also more patients who met the APS clinical criteria.

Conclusion: The sex difference of the cut-off value for DRVVT LA test is confirmed on multiple systems, the female-specific cut-off is lower than regardless of sex cut-off and may lead to more female patients being considered as high-risk population for APS.

Background: Catheter-directed treatment (CDT) is an innovative treatment for patients with elevated risk pulmonary embolism (PE) to resolve embolus and restore pulmonary perfusion.

Objectives: We aimed to analyse the use and the benefit of CDT in PE patients in Germany.

Methods: The German nationwide inpatient sample was used to include all hospitalizations of patients with PE from 2005 to 2020 in Germany. PE patients were stratified for CDT usage. Temporal trends and the impact of CDT on case fatality and other outcomes were investigated.

Results: Overall, 1,373,084 hospitalizations of patients with PE (55.9% aged ≥70 years; 53.0% females) were included in this study from 2005 to 2020, and among these, 427,238 (31.1%) patients were categorized as having elevated-risk PE and 3330 (0.2%) were treated with CDT with annual increase from 0.17% (2005) to 0.51% (2020). PE patients of younger age, male sex, with previous surgery, and elevated-risk PE were more often treated with CDT. In patients with elevated risk-PE, CDT attributed to a lower observed rate of major adverse cardiac and cerebrovascular events (major adverse cardiac and cerebrovascular events [MACCE]; 28.2% vs 34.2%; P < .001) and in-hospital case fatality (24.9% vs 31.0%; P < .001). CDT was associated with reduced MACCE (OR, 0.91; 95% CI, 0.83-0.99) and with a trend toward lower case fatality (OR, 0.92; 95% CI, 0.84-1.01). The benefit of CDT regarding case fatality was age-dependent.

Conclusion: Although the annual rate of CDT increased in Germany between 2005 and 2020, only 0.2% of the PE patients were treated with CDT. Selection criteria for CDT treatment were younger age, male sex, previous surgery, and elevated risk-PE. CDT treatment was associated with reduced MACCE and case-fatality rate in PE patients with elevated-risk PE.

Background: Reduced effect of antiplatelet therapy has been reported in patients with ST-segment elevation myocardial infarction (STEMI). This could partly be explained by an increase of highly reactive immature platelets.

Objectives: To investigate changes in platelet maturity and reactivity after acute STEMI.

Methods: Patients diagnosed with STEMI, admitted for primary percutaneous coronary intervention, and treated according to international guidelines, were included. Blood samples were obtained within 24 hours after admission and at 2- to 3-months follow-up. Platelet maturity and reactivity using multicolor flow cytometry with SYTO-13 to categorize platelet maturity, whole blood platelet aggregation, serum thromboxane B2 levels, and standard immature platelet markers (eg, immature platelet count and fraction, and mean platelet volume) were measured.

Results: A total of 44 STEMI patients were included. The reactivity of immature platelets was consistently higher at baseline and at follow-up when compared to the entire platelet population and the mature platelet population (all P values < .05). The expression of CD63 (a dense granule marker) in immature platelets was consistently high compared to the entire platelet population and the mature platelet population and did not change from baseline to follow-up (P values > .24). Additionally, a positive significant correlation was found between standard immature platelet markers and the expression of CD63 on platelets both at baseline and follow-up (rho ranging from 0.32 to 0.62, all P values < .05).

Conclusion: Immature platelets represent a highly reactive platelet subpopulation crucial for the overall platelet reactivity, partly due to a high expression of dense granules. Despite treatment with loading and maintenance doses of antiplatelet therapy, the reactivity of immature platelets remained high in STEMI patients.

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.