Thrombosis Journal最新文献

Background: Coagulation dysfunction significantly impacts sepsis prognosis. Standardized methods for evaluating anticoagulant efficacy and safety in this population remain lacking. This study aimed to assess the efficacy and safety of anticoagulant therapy in sepsis patients.

Methods: We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing anticoagulants against placebo/no treatment in sepsis patients. The reduction in 28/30-day all-cause mortality or the regression of disseminated intravascular coagulation (DIC) was regarded as efficacy endpoints, while bleeding complications constituted the most prevalent adverse events.

Results: Eighteen RCTs involving 8053 patients were included. Anticoagulant therapy demonstrated an 8% mortality risk reduction versus placebo (relative risk [RR] 0.92, 95% CI 0.86-0.98; P = 0.02). In six studies of baseline DIC patients, anticoagulants showed non-significant mortality reduction (RR 0.87, 95% CI 0.62-1.22; P = 0.42) but significantly enhanced DIC regression (RR 1.62, 95% CI 1.32-2.00; P < 0.00001). Anticoagulants increased bleeding risk (RR 1.32, 95% CI 1.16-1.49; P < 0.0001).

Conclusion: Anticoagulant therapy confers survival benefit in the overall sepsis population despite increased bleeding risk. While improving DIC regression in sepsis-associated DIC, mortality reduction in this subgroup lacked statistical significance. Further research should clarify anticoagulants' role in DIC-specific sepsis management.

Cancer-associated thrombosis (CAT), especially venous thromboembolism (VTE), is the second highest cause of mortality in cancer patients, following the cancer itself. Notably, among patients with thrombosis, cancer is the most common underlying cause of death, highlighting the strong interrelationship between these conditions. Tumour cells primarily promote a prothrombotic environment through activation of procoagulant properties of the host cells. Additionally, chemotherapy, radiotherapy and hormone treatments may amplify the thrombotic risk in cancer patients. Consequently, both arterial thromboses, including myocardial infarction (MI) and ischemic stroke (IS), and venous thrombosis, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), are significantly more prevalent among patients with malignancies. This review will discuss the association between cancer and thrombosis, illustrate the most common risk factors and discuss the direct and indirect molecular mechanisms involved.

Background: Asundexian, a novel oral Factor XIa (FXIa) inhibitor, targets the intrinsic coagulation pathway to prevent thrombosis while potentially reducing bleeding risk compared to direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs). This systematic review synthesizes clinical evidence on its safety, efficacy, and pharmacological properties in managing arterial and venous thrombotic events.

Methods: Following PRISMA guidelines, we searched PubMed, Embase, Scopus, Cochrane Library, ClinicalTrials.gov, and Web of Science for clinical trials and observational studies on asundexian until January 2025. Inclusion criteria included studies reporting safety, efficacy, and pharmacokinetics/pharmacodynamics (PK/PD) outcomes. Two reviewers independently screened studies and extracted data, with quality assessed using the Cochrane Risk of Bias 2 tool.

Results: Eleven trials (n > 21,000, phases 1-3) were included. Asundexian suppressed FXIa activity, with phase 2 trials (e.g., PACIFIC-AF, PACIFIC-STROKE) showing reduced bleeding compared to apixaban. However, the phase 3 OCEANIC-AF trial was terminated early due to inferior efficacy in atrial fibrillation, with higher stroke/systemic embolism rates (2.5%) versus apixaban. PK/PD data support once-daily dosing with minimal drug interactions. Safety concerns include potential abnormal uterine bleeding, with limited data.

Conclusion: Asundexian shows promise in reducing bleeding but lacks efficacy in high-risk settings like atrial fibrillation. Ongoing trials are needed to define its role in specific thrombotic conditions.

Clinical trial number: Not applicable.

Background: Accurate coagulation parameter reference intervals are crucial for diagnosing bleeding disorders and thromboembolic diseases. However, reference intervals vary across populations due to genetic, environmental, and demographic factors. This study aimed to establish localized coagulation reference intervals for healthy adults of Debre Berhan, Northeast Ethiopia, addressing the current reliance on non-local values.

Methods: A community-based cross-sectional study was conducted in Debre Berhan, Northeast Ethiopia, from October-December 2024. We recruited 240 healthy adults (120 of each gender) using convenience sampling. Participants were interviewed face-to-face using a pre-tested questionnaire on KoBoToolbox to collect demographic data. Aseptically drawn venous blood was analyzed for coagulation parameters using Sysmex CA-104 coagulation analyzer. Stata 17 was used for data analysis, with reference intervals determined by the 2.5th and 97.5th percentiles. Gender differences were assessed using the Mann-Whitney U test (p < 0.05 significance).

Results: The established 95% coagulation reference intervals (2.5th -97.5th percentile) were: Prothrombin time (8.5-13.0 sec), international normalized ratio (0.7-1.1), and activated partial thromboplastin time (21.6-37.9 sec). Males exhibited significantly higher median PT (10.4 Vs. 9.8 sec, p = 0.0006) and INR (0.9 Vs. 0.84, p = 0.0006) values compared to females.

Conclusion: This study's findings strongly support the adoption of population-specific reference intervals to ensure accurate diagnoses and improve patient safety within the Debre Berhan adult population. The observed gender-related differences in Prothrombin time and international normalized ratio values further highlight the need for gender-specific reference intervals to improve clinical decision-making and prevent potential misinterpretations of coagulation test results.

Background: Hereditary antithrombin deficiency (HATD) is a rare disease caused by mutations in the SERPINC1 gene characterized with venous thromboembolism and/or arterial thrombotic events. We identified a proband with recurrent arterial and venous thrombosis at multiple anatomical sites and subsequently performed comprehensive thrombophilia screening and genetic analysis within the kindred.

Methods: Mutation screening of the SERPINC1 gene in the proband and family members was conducted using Sanger sequencing. Wild-type and mutant (c.473T > A; p.Leu158Gln) SERPINC1 expression plasmids were constructed and transiently transfected into HEK293T cells. Functional consequences of the variant were assessed through immunoblotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and computational structural analysis.

Results: Thrombophilia evaluation revealed significantly reduced antithrombin activity (46.2%) in the proband. Sanger sequencing identified an unreported heterozygous missense variant (c.473T > A; p.Leu158Gln) in SERPINC1. Cellular studies demonstrated that this mutation reduced both the quantity and functional activity of secreted antithrombin. Immunoblot analysis indicated a slightly faster migration of the mutant protein compared to wild-type, while immunofluorescence revealed abnormal cytoplasmic aggregation. Bioinformatics analysis confirmed substitution of leucine-158 by glutamine without disruption of conserved disulfide bonds (Cys40-Cys160, Cys128-Cys182, Cys247-Cys430) or N-glycosylation sites (Asn128, Asn167, Asn187, Asn224).

Conclusion: We establish the c.473T > A (p.Leu158Gln) variant in SERPINC1 as a pathogenic mutation underlying type I HATD, characterized by impaired secretion, cytoplasmic retention, and reduced functional activity of the mutant protein.

Background: Haemophilia, caused by deficiencies in factor VIII or IX, leads to deep tissue bleeding and haemophilic arthropathy. Bleeding, arthropathy, and the perioperative period of surgery for arthropathy are associated with severe pain. To avoid this pain, patients may compensate by overloading other parts of the body, potentially resulting in pain or secondary damage in areas distant from the primary site. This study investigates the use of infrared thermography (IRT) to monitor whole-body surface temperatures in people with haemophilia and to explore the potential of infrared thermography for early detection of compensatory overload.

Methods: A cross-sectional study involved 24 people with haemophilia aged 6-76 years old, experiencing pain after bleeding, post-orthopaedic surgery, or haemophilic arthropathy. Thermal images were captured with IRT and analyzed using software that utilises deep learning for whole-body temperature mapping.

Results: Increases in temperature indicative of overload were observed in areas distant from the affected site, either on the same side (vertical pattern) or on the opposite side (diagonal pattern) relative to the site of pain. These patterns were observed in 13 of 14 participants with haemophilic arthropathy, all post-orthopaedic surgery participants, and 5 of 6 after bleeding.

Conclusions: Temperature increases occurred in areas beyond the painful area, suggesting strain even in asymptomatic regions. People with haemophilia experiencing pain may require careful monitoring and treatment of surrounding areas. Our findings could aid in diagnosing haemorrhage and local inflammation while informing treatment decisions.

Clinical trial registration: Not applicable.

Background: Anticoagulant therapy is considered useful for sepsis patients with disseminated intravascular coagulation (DIC); however, the efficacy of combination therapy with anticoagulants is still under investigation.

Methods: We evaluated anticoagulant use in 1,770 patients with sepsis-induced DIC from 314 institutions by analyzing postmarketing survey data on plasma-derived antithrombin (AT) concentrates. DIC was defined as a DIC score above 4 according to the Japanese Association for Acute Medicine (JAAM). We divided patients into quartiles according to JAAM-defined DIC and Sequential Organ Failure Assessment (SOFA) scores to determine the efficacy of concomitant recombinant thrombomodulin (rTM) following AT supplementation, and we performed a propensity score-adjusted analysis.

Results: The 28-day mortality rate after AT administration was 24.1%. We categorized patients on the basis of a JAAM-defined DIC score of 6 and a SOFA score of 9, because the patients' median JAAM-defined DIC and SOFA scores were 5 and 9, respectively. Among patients with JAAM-defined DIC scores >6 and SOFA scores >9, patients treated with AT followed by rTM (concomitant rTM use) had a significantly lower mortality rate (28.5%) than did those treated without concomitant rTM (40.0%) (p = 0.031). However, among patients with JAAM-defined DIC scores of four or five, the patients treated with concomitant rTM had a significantly greater mortality rate than did those not treated with concomitant rTM, irrespective of whether their SOFA score was below or above 9 (18.5% vs. 10.1%, p = 0.036 and 37.0% vs. 24.3%, p = 0.018, respectively). The incidence of serious bleeding- related adverse events did not differ between patients with and without concomitant rTM treatment.

Conclusions: efficacy of rTM administration following AT supplementation in patients with sepsis-induced DIC is controversial, and the evidence is restricted to decreasing mortality rates in patients with JAAM-defined DIC scores >6 and SOFA scores>9. However, further studies are needed to confirm these findings.