Thrombosis Journal最新文献

The link between venous thromboembolism (VTE) and cancer is well known. VTE could be the initial sign of an occult malignancy. There are more diagnoses of cancer after an unprovoked VTE compared to a provoked VTE, with a reported prevalence between 4.5% and 5.6% over 12 months, within the first 6 months of VTE diagnosis. There are no recommended guidelines and scores yet adopted in clinical practice, but many studies support occult cancer screening in unprovoked VTE patients. We report the case of a patient with a history of unprovoked pulmonary embolism (PE) diagnosed with bronchopulmonary neoplasm in an advanced stage one year after the thromboembolic event. When the cancer was first diagnosed, the patient's condition was already serious, being too late for the adoption of measures meant to decrease the risk of mortality and increase the duration of survival. We wanted to emphasize the importance of occult cancer screening in patients with unprovoked VTE and the fact that early cancer diagnosis reduces the risk of cancer progression, decreasing mortality and morbidity related to it.

Background: About 13-25% of cerebral venous thrombosis (CVT) cases lack clear etiology, which may be associated with underlying genetic factors. This study aims to investigate genetic factors in CVT patients using whole exome sequencing (WES).

Methods: Thirty-eight CVT patients hospitalized underwent WES. 977 subjects with WES data from a community cohort study --the Shunyi cohort were as the control group. Using bioinformatics analysis, differential genes with rare damaging variants between two groups were filtered (P < 0.05). KEGG enrichment analysis was performed on the screened genes to identify pathways associated with CVT.

Results: Through analysis of medical history, routine tests, and imaging examinations, the etiology of 38 patients: 8 cases of antiphospholipid syndrome, 6 cases with hematologic diseases, 3 cases of protein C deficiency, and 2 cases of protein S deficiency. Five cases occurred during pregnancy or puerperium, and 3 cases had a history of oral contraceptive use, and so on. The etiology was unknown in 12 cases (31.6%), and the etiology of 4 patients were further clarified through WES: F9 c.838 + 1_838 + 16del, Hemizygote: F9 EX1-EX7 Dup; CBS c.430G > A, CBS c.949 A > G; F2 c.1787G > A; SERPINC1 c.409-11G > T. Comparing the WES data of two groups, a total of 179 different genes with rare damaging variants were screened (P < 0.05), with 5 genes of interest (JAK2, C3, PROC, PROZ, SERPIND1). Enrichment analysis of the 179 different genes revealed the complement and coagulation pathway and the mitogen activated protein kinases (MAPK) pathway were associated with CVT.

Conclusion: For CVT patients with unknown etiology, WES could help identify the cause of CVT early, which is of great significance for treatment decisions and prognosis. In addition to the complement and coagulation pathway, MAPK pathway is associated with CVT, potentially related to platelet regulation and inflammatory response.

Background: Pulmonary embolism (PE) is a life-threatening thromboembolic disease for which there is limited evidence for effective prevention and treatment. Our goal was to determine whether genetically predicted circulating blood cell traits could influence the incidence of PE.

Methods: Using single variable Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) analyses, we identified genetic associations between circulating blood cell counts and lymphocyte subsets and PE. GWAS blood cell characterization summary statistics were compiled from the Blood Cell Consortium. The lymphocyte subpopulation counts were extracted from summary GWAS statistics for samples from 3757 individuals that had been analyzed by flow cytometry. GWAS data related to PE were obtained from the FinnGen study.

Results: According to the SVMR and reverse MR, increased levels of circulating white blood cells (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.81-0.95, p = 0.0079), lymphocytes (OR: 0.90, 95% CI: 0.84-0.97, p = 0.0115), and neutrophils (OR: 0.88, 95% CI: 0.81-0.96, p = 0.0108) were causally associated with PE susceptibility. MVMR analysis revealed that lower circulating lymphocyte counts (OR: 0.84, 95% CI: 0.75-0.94, p = 0.0139) were an independent predictor of PE. According to further MR results, this association may be primarily related to HLA-DR⁺ natural killer (NK) cells.

Conclusions: Among European populations, there is a causal association between genetically predicted low circulating lymphocyte counts, particularly low HLA-DR⁺ NK cells, and an increased risk of PE. This finding supports observational studies that link peripheral blood cells to PE and provides recommendations for predicting and preventing this condition.

Background: Risks of recurrence and major bleeding with extended anticoagulation in Asian patients with venous thromboembolism (VTE) are similar to those in non-Asian patients but risks according to baseline risk factor profiles is not well documented.

Methods: Subgroup analysis of two randomized trials, which compared once-daily rivaroxaban (20 mg or 10 mg) with placebo or aspirin (100 mg) for extended treatment in Asian patients with VTE who had completed 6-12 months of anticoagulation. Index events were classified as unprovoked, provoked by major persistent risk factors, minor persistent risk factors, minor transient risk factors, or major transient risk factors. One-year cumulative risks of recurrent VTE were calculated for these risk factor profiles.

Results: 367 patients received rivaroxaban, 159 aspirin, and 48 placebo. For patients with unprovoked VTE, one-year cumulative incidences of recurrence in the 202 patients given rivaroxaban, the 89 given aspirin and the 28 given placebo were 1.6%, 5.8%, and 14.8%, respectively. For patients with VTE provoked by minor persistent risk factors, these incidences were 0% in the 74 patients given rivaroxaban, 9.3% in the 36 given aspirin, and 0% in the 12 given placebo. No recurrent VTE occurred in patients with VTE provoked by major persistent or transient risk factors or minor transient risk factors. Rivaroxaban was not associated with a significant increase in major bleeding.

Conclusions: Rivaroxaban seems to be an effective and safe option for extended treatment in Asian patients, especially those presenting with unprovoked VTE. Subgroups of patients with provoked risk factors were too small to draw meaningful conclusions.

Trial registration: NCT00439725 and NCT02064439.

Background: Von Willebrand factor (vWF) plays a crucial role in hemostasis, acting as a key factor for platelet adhesion/aggregation and as a transport protein for coagulation factor VIII. vWF is secreted as a giant multimer, and it undergoes shear stress-dependent cleavage by a specific metalloproteinase in plasma. Among vWF multimers, high-molecular-weight (large) multimers are essential for hemostasis. Acquired von Willebrand syndrome, linked to various conditions, is a hemostatic disorder due to reduced vWF activity. Extracorporeal membrane oxygenation (ECMO), utilized recently for out-of-hospital cardiac arrest patients, generates high shear stress inside the pump. This stress may induce a conformational change in vWF, enhancing cleavage by a specific metalloproteinase and thereby reducing vWF activity. However, no study has investigated the effects of ECMO on vWF-related factors in patients receiving or not receiving ECMO. This study aimed to elucidate the relationship between ECMO treatment and acquired von Willebrand syndrome-related factors in patients with out-of-hospital cardiac arrest.

Methods: This study included patients with cardiogenic out-of-hospital cardiac arrest admitted to our hospital. The patients were categorized into two groups (ECMO and non-ECMO) based on the presence or absence of ECMO treatment. Plasma samples were collected from patients admitted to the emergency department (days 0-4). The vWF antigen (vWF: Ag), vWF ristocetin cofactor activity (vWF: RCo), and factor VIII activity were measured. Additionally, a large multimer of vWF was evaluated through vWF multimer analysis, utilizing western blotting to probe vWF under non-reducing conditions.

Results: The ECMO and non-ECMO groups included 10 and 22 patients, respectively. The median ECMO treatment in the ECMO group was 64.6 h. No differences in vWF: Ag or factor VIII activity were observed between the two groups during the observation period. However, the ECMO group exhibited a decrease in large vWF multimers and vWF: RCo during ECMO. Strong correlations were observed between vWF: RCo and vWF: Ag in both groups, although the relationships were significantly different between the two groups.

Conclusions: ECMO treatment in patients with out-of-hospital cardiac arrest resulted in the loss of large vWF multimers and decreased vWF activity. Hence, decreased vWF activity should be considered as a cause of bleeding during ECMO management.

Background: We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL.

Methods: A systematic search for studies that assessed the association between PAI-1 4G/5G polymorphism and RPL risk published in search sources, PubMed/Medline, ISI Web of Knowledge, Scopus, and Google Scholar till January 2024 was conducted.

Results: There were 23 case-control studies in total, with a high degree of statistical heterogeneity among them which indicated the need for subgroup analysis. We found a significant positive association between the risk of RPL and 4G/4G PAI-1 (OR: 2.57; 95% CI: 1.69-3.90), likewise 4G/5G (OR: 2/02 95% CI: 1.39-2.92) and mixed genotype (4G/4G+4G/5G) (OR: 2.31 95% CI: 1.81-2.93). Considering the ethnicity, the 4G/4G polymorphism is significantly associated with Asian descent (OR: 2.10; CI: 1.65-2.69) while the strong association (OR: 6.47; CI: 3.23-12.97) observed in the Greater Middle East descent is not statistically significant (P=0.16). PAI-1 4G/5G polymorphism association with RPL was only significant in Greater Middle East descent (OR: 2.93; CI: 2.41-3.56), and mixed genotype was significantly associated with RPL in Asian (OR: 2.37; CI: 1.55-3.61), Greater Middle East (OR: 3.01; CI: 2.16-4.19), and European populations (OR: 1.38; CI: 0.91-2.10). The association between RPL and PAI-1 4G/4G was significant for RPLs both under 12 weeks (OR: 1.82; 95% CI: 1.34-2.47), and under 24 weeks (OR: 1.46; 95% CI: 1.11-1.92), while considering heterozygote form the association was only significant for RPLs under 24 weeks (OR: 1.91; 95% CI: 1.58-2.31). Regarding the mixed genotype, there is a significant positive association between PAI-1 and RPL for RPLs under 12 weeks (OR: 2.09; 95% CI: 1.49-2.93), and under 24 weeks (OR: 2.10; 95% CI: 1.52-2.92).

Conclusions: Our findings indicate a significant association between the rs1799762 PAI-1 polymorphism and the risk of RPL.

Background: Clinical decision support systems (CDSS) have been utilized as a low-cost intervention to improve healthcare process measures. Thus, we aim to estimate CDSS efficacy to optimize adherence to oral anticoagulant guidelines in eligible patients with atrial fibrillation (AF).

Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through August 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI).

Prospero id: CRD42023471806.

Results: We included nine RCTs with a total of 25,573 patients. There was no significant difference, with the use of CDSS compared to routine care, in the number of patients prescribed anticoagulants (RR: 1.06, 95% CI [0.98, 1.14], P = 0.16), the number of patients prescribed antiplatelets (RR: 1.01 with 95% CI [0.97, 1.06], P = 0.59), all-cause mortality (RR: 1.19, 95% CI [0.31, 4.50], P = 0.80), major bleeding (RR: 0.84, 95% CI [0.21, 3.45], P = 0.81), and clinically relevant non-major bleeding (RR: 1.05, 95% CI [0.52, 2.16], P = 0.88). However, CDSS was significantly associated with reduced incidence of myocardial infarction (RR: 0.18, 95% CI [0.06, 0.54], P = 0.002) and cerebral or systemic embolic event (RR: 0.11, 95% CI [0.01, 0.83], P = 0.03).

Conclusion: We report no significant difference with the use of CDSS compared to routine care in anticoagulant or antiplatelet prescription in eligible patients with AF. CDSS was associated with a reduced incidence of myocardial infarction and cerebral or systemic embolic events.

Background: Recent guidelines recommend using direct oral anticoagulants (DOACs) as first-line agents in patients with non-valvular atrial fibrillation (NVAF). Research is currently investigating the use of Apixaban in underweight patients, with some results suggesting altered pharmacokinetics, decreased drug absorption, and potential overdosing in this population. This study examined the effectiveness and safety of standard Apixaban dosing in adult patients with atrial NVAF weighing less than 50 kg.

Methods: This is a retrospective cohort study conducted at King Abdulaziz Medical City (KAMC); adult patients with a body mass index (BMI) below 25 who received a standard dose of Apixaban (5 mg twice daily) were categorized into two sub-cohorts based on their weight at the time of Apixaban initiation. Underweight was defined as patients weighing ≤ 50 kg, while the control group (Normal weight) comprised patients weighing > 50 kg. We followed the patients for at least one year after Apixaban initiation. The study's primary outcome was the incidence of stroke events, while secondary outcomes included bleeding (major or minor), thrombosis, and venous thromboembolism (VTE). Propensity score (PS) matching with a 1:1 ratio was used based on predefined criteria and regression model was utilized as appropriate.

Results: A total of 1,433 patients were screened; of those, 277 were included according to the eligibility criteria. The incidence of stroke events was lower in the underweight than in the normal weight group at crude analysis (0% vs. 9.1%) p-value = 0.06), as well in regression analysis (OR (95%CI): 0.08 (0.001, 0.76), p-value = 0.002). On the other hand, there were no statistically significant differences between the two groups in the odds of major and minor bleeding (OR (95%CI): 0.39 (0.07, 2.03), p-value = 0.26 and OR (95%CI): 1.27 (0.56, 2.84), p-value = 0.40, respectively).

Conclusion: This exploratory study revealed that underweight patients with NVAF who received standard doses of Apixaban had fewer stroke events compared to normal-weight patients, without statistically significant differences in bleeding events. To confirm these findings, further randomized controlled trials with larger sample sizes and longer observation durations are required.

Background: This study aimed to evaluate the association of antiphospholipid antibodies (aPL) and conventional markers of coagulation with ischemic and bleeding risk in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).

Methods: In this prospective two-center observational cohort study, patients with AF and an indication for oral anticoagulation (OAC) were enrolled after PCI. Blood was drawn on day 1-3 after PCI. Dilute Russell's viper venom time was used to determine lupus anticoagulant (LA) in OAC-free plasma. Anti-cardiolipin (aCL) IgG, IgM, and anti-β2-Glycoprotein 1 (aβ2GP1) IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). Fibrinogen (FIB), d-dimer, and prothrombin fragment 1 and 2 (PF 1 + 2) were measured in citrated plasma. The primary ischemic outcome was time to major adverse cardiovascular events (MACE; death, myocardial infarction, or stroke) assessed at 6 months. Bleeding was defined according to International Society on Thrombosis and Haemostasis.

Results: 158 patients were enrolled between May 2020 and May 2021 on day 1-3 after PCI. The median age was 78 years (interquartile range [IQR] 72-82), 111 (70%) were male, and 39 (25%) presented with acute coronary syndrome. D-dimer was elevated in 74 (47%) patients, FIB was increased in 40 (25%) and PF1 + 2 in 68 (43%) patients. 32 (20%) patients had ≥ 1 antiphospholipid antibody elevated (aPL; LA: 19 [12%], aCL: 14 [9%], aβ2GP1: 2 [1%]). The presence of aPL was neither significantly associated with MACE (HR 1.46, 95% CI [0.39-5.49], p = 0.579), nor bleeding (HR 1.07 [0.30-3.84], p = 0.917). Elevated d-dimer was significantly associated with higher risk for MACE (HR 5.06 [1.09-23.41], p = 0.038) and major bleeding (HR 7.04 [1.58-31.47], p = 0.011). Elevated D-dimer increased the predictive capacity of HAS-BLED for major bleedings (HAS-BLED: AUC 0.71 [0.60-0.83] vs. HAS-BLED + d-dimer: AUC 0.79 [0.70-0.88]; p = 0.025). Increased levels of FIB were associated with higher risk for MACE (HR 3.65 [1.11-11.96], p = 0.033).

Conclusion: Biomarkers of coagulation might be suitable to assess ischemic and bleeding risk in patients with AF following PCI.