BACKGROUND: Thromboelastography (TEG) is used in various clinical settings to assess clot formation, strength, and lysis. It is unknown whether TEG measures correspond to plasma fibrin clot characteristics. METHODS: In 9...BACKGROUND: Thromboelastography (TEG) is used in various clinical settings to assess clot formation, strength, and lysis. It is unknown whether TEG measures correspond to plasma fibrin clot characteristics. METHODS: In 90 individuals free of cardiovascular disease (51 [56.7%] women, aged 49.3 ± 5.2 years, body-mass index [BMI], 26 [23.8-29.3] kg/m) we assessed whole blood clot parameters (reaction [R] and clot formation [K] time, clot growth kinetics [angle], maximum amplitude [MA], and clot lysis [LY30]) using the TEG 6s analyzer (Haemonetics, Boston, US), plasma clot permeability (Ks), and clot lysis time (CLT) using three assays: (1) by Pieters (CLT-2018), (2) by Lisman (CLT), and (3) by Carter (Lys50). RESULTS: There were associations of Ks with K time (R = 0.29, p = 0.0053), angle (R = -0.31, p = 0.0033), and MA (R = -0.47, p < 0.0001), while CLT tended to correlate with LY30. In women compared to men Ks was 8.4% lower corresponding to 7% higher MA (both p < 0.001). In obese (n = 19, 21.1%) vs. non-obese individuals angle was 5% larger (p = 0.029) but BMI did not correlate with TEG measures. TEG parameters and fibrin clot properties were unaffected by smoking, hypertension or hyperlipidemia. More efficient fibrinolysis (LY30 > 2.6%) was detected in 15 (16.7%) individuals who had also shorter CLT-2018 and CLT (both p < 0.05). Hypofibrinolysis (CLT-2018 > 300 min; n = 8, 8.9%) was detected only using CLT with no differences in TEG indices or Lys50. CONCLUSIONS: TEG and plasma fibrin clot properties are complementary methods for assessing hemostasis, however, fibrin clot properties better reflect the impact of clinical risk factors on fibrinogen modification.
INTRODUCTION: Delayed diagnosis (DDx) of Venous thromboembolism (VTE) contributes to preventable mortality. Our prior work resulted in an electronic Clinical Quality Measure (eCQM) for Diagnostic Delay of VTE (DOVE) [1]...INTRODUCTION: Delayed diagnosis (DDx) of Venous thromboembolism (VTE) contributes to preventable mortality. Our prior work resulted in an electronic Clinical Quality Measure (eCQM) for Diagnostic Delay of VTE (DOVE) [1] and a phenotyping algorithm to identify cases of VTE [2]. Current work incorporates voices of VTE survivors to extend that research. METHODS: We interviewed 8 and surveyed 68 VTE survivors, coded and categorized text, and uploaded data into the DOVE qualitative database. Drawing on this database and patient self-management literature, notably the concepts: patient engagement [3,4] and patient activation [5,6] we developed a model to guide "Successful Living with VTE." RESULTS: The 76 VTE survivors provided rich descriptions of their journeys from questioning that something may be wrong to making recommendations to help others. Participants were articulate, highly educated, mostly female and white, and geographically diverse. Recommendations were defined as "Recommendations for patients, providers and health care sites targeted to achieve timely VTE diagnosis and treatment across the trajectory from first concern through follow-up care." Patients are advised to be assertive, obtain education and bring a support person. Providers are advised to listen, be knowledgeable and consider genetic testing. CONCLUSIONS: The recommendations make common sense, do not require expensive equipment or intensive training or extra staff. VTE survivors' recommendations merged with the science of patient self-management provided the model's structure. The model will inform a VTE curriculum and clinical decision support application, and guide research to promote successful living with VTE.
BACKGROUND: Patients with gastrointestinal (GI) cancer are at increased risk of venous thromboembolism (VTE), which is an important cause of mortality. Risk stratification of VTE in GI cancer remains challenging. OBJECTI...BACKGROUND: Patients with gastrointestinal (GI) cancer are at increased risk of venous thromboembolism (VTE), which is an important cause of mortality. Risk stratification of VTE in GI cancer remains challenging. OBJECTIVES: To investigate whether assessment of the coagulation system can predict VTE risk in three GI tumor types. METHODS: We used a nested case-control design within the MICA cohort (total N = 81), including 27 patients who developed VTE during follow-up and 54 matched non-VTE controls. The subgroup distribution was esophageal cancer (n = 42), pancreatic cancer (n = 18), and colorectal cancer (n = 21). Plasma samples were analyzed using a multifaceted approach incorporating tissue factor (TF) measurement, thrombin generation, and endothelial function testing within an artificial vessel model. Conditional logistic regression was used to evaluate associations between coagulation parameters and VTE risk. RESULTS: TF concentrations did not differ between patients with and without VTE across esophageal, colorectal, and pancreatic cancers. In esophageal cancer, prolonged lag time, as well as higher endogenous thrombin potential and peak values in the artificial vessel model, were significantly associated with an increased risk of VTE (OR = 9.95, 95% CI 1.21-81.54; OR = 5.15, 95% CI 1.07-25.00; OR = 10.75, 95% CI 1.31-90.91). No significant differences in coagulation-related parameters were observed in pancreatic or colorectal cancer patients. CONCLUSION: Abnormal coagulation may be associated with VTE risk mainly in esophageal cancer, suggesting that VTE biomarkers may differ by cancer type and require further investigation in larger cohorts.
Internal hemorrhage remains a critical challenge requiring immediate intervention. Recent advances in biomaterials have positioned fibrin hemostatic patches (FHPs) as a promising therapeutic option through targeted fibri...Internal hemorrhage remains a critical challenge requiring immediate intervention. Recent advances in biomaterials have positioned fibrin hemostatic patches (FHPs) as a promising therapeutic option through targeted fibrinogen-to-fibrin conversion at the injured organ; however, insufficient understanding of the stoichiometric coupling between active components of FHP may limit its coagulation performance. Here, we report a novel FHP (nFHP) through orthogonal optimization of fibrinogen, thrombin, and calcium chloride. Systematic screening identified fibrinogen concentration as the primary determinant of clotting time, with fibrinogen-to-thrombin and fibrinogen-to-calcium chloride ratios further impacting. nFHP, fabricated with the optimal formulation (17 mg/cm fibrinogen, 40 IU/cm thrombin, 115 μg/cm calcium chloride), achieved rapid fibrin network formation and superior adhesive strength on the porcine aorta, surpassing commercial FHP (cFHP). In vivo evaluations across hepatic resection, cardiac stab wound, and arterial hemorrhage models demonstrated nFHP's universal efficacy, achieving the minimal blood loss compared to commercial products. Our work identifies stoichiometric proportion as a key factor in fibrin-based biomaterial rational design and provides a translatable solution for uncontrolled internal hemorrhage.
INTRODUCTION: Extended half-life factor IX concentrates (FIX-EHL) have been shown to improve clinical outcomes and reduce treatment burden in patients with hemophilia B (HB). OBJECTIVES: To analyze the differences in pha...INTRODUCTION: Extended half-life factor IX concentrates (FIX-EHL) have been shown to improve clinical outcomes and reduce treatment burden in patients with hemophilia B (HB). OBJECTIVES: To analyze the differences in pharmacokinetic (PK) and clinical parameters one year before and after the PK-guided switch from standard half-life FIX (FIX-SHL) to FIX-EHL in patients with severe/moderate HB on prophylaxis. METHODS: A multicenter, comparative, observational, sequential, retrospective, and multidisciplinary study was conducted. PK parameters were calculated with WAPPS-Hemo®, and annualized total (ABR) and joint bleeding rates, the t ratio and area under the curve (AUC), FIX consumption, infusion frequency, and cost were recorded. RESULTS: A total of 21 patients (9 pediatric and 12 adult) with HB who switched from FIX-SHL to FIX-EHL were analyzed. All PK parameters improved significantly, with median improvement ratios for t and AUC of 4.1 (IQR: 3.4-4.8) and 4.2 (IQR: 2.6-5.0), respectively. Regarding clinical outcomes, the difference in ABR reached statistical significance and among the 6 patients with target joints, 5 (83.3 %) achieved resolution after switching. Infusion frequency and weekly dose were reduced by 50.0 % and 56.3 %, respectively, avoiding 52.1 (IQR: 26.1-67.8) injections and 130,357.3 (IQR: 5142.9-203,357.3) IU of FIX per patient per year. However, the switch resulted in an additional cost of € 28,254.9 (IQR: 4432.1- 44,060.8) per patient per year. CONCLUSIONS: The PK-guided switch from FIX-SHL to FIX-EHL was associated with improvements in all PK parameters, and a significant clinical benefit was also demonstrated with the reduction of the bleeding rates. Following the switch, the weekly dose and administration frequency were reduced; however, this did not result in a cost reduction.
Venous thromboembolism is a major preventable complication among orthopedic inpatients, yet existing risk scores and correlation-driven models often miss complex physiological interactions and provide limited interpretab...Venous thromboembolism is a major preventable complication among orthopedic inpatients, yet existing risk scores and correlation-driven models often miss complex physiological interactions and provide limited interpretability. We propose Causal-Aware Risk Embedding Network (CARE-Net), a causal representation learning framework for VTE prediction on structured clinical data. CARE-Net first infers a directed causal graph among laboratory, demographic, and therapeutic variables, then performs message passing strictly along causal directions to construct mechanism-aligned patient embeddings. A causal contrastive objective further aligns patients with similar causal signatures, enhancing robustness and suppressing spurious associations. Extensive comparisons with statistical, ensemble, deep tabular, transformer-based, and graph-based baselines show that CARE-Net delivers consistently superior discrimination and a more balanced sensitivity-specificity profile. Ablation and feature-importance analyses confirm that each causal component contributes meaningfully and that learned risk factors align with established clinical pathways. These findings suggest that embedding causal structure into representation learning offers a principled route to reliable VTE decision support in orthopedic care.
PURPOSE: This systematic-review and meta-analysis investigated the effectiveness of radiosynoviorthesis (RSO) on clinical outcomes in male persons with haemophilia (PwH) and evaluated the quality of existing evidence. ME...PURPOSE: This systematic-review and meta-analysis investigated the effectiveness of radiosynoviorthesis (RSO) on clinical outcomes in male persons with haemophilia (PwH) and evaluated the quality of existing evidence. METHODS: Literature searches in PubMed and Web of Science identified 31 studies, with 17 included in the meta-analysis. Random-effects models were computed to analyse RSO-related changes in bleeding frequency, pain, synovial hypertrophy, and orthopaedic joint score. Due to insufficient data, Range of Motion (RoM) changes could not be meta-analytically calculated. Mean differences (MD) for bleeding frequency and standardized mean differences (SMD) for the remaining outcomes were computed. RESULTS: Results showed significant reductions in bleeding frequency at six months (MD = -5.93 [95 %-CI: -7.80, -4.06], p < 0.001, k = 10) and twelve months (MD = -7.83 [95 %-CI: -12.11, -3.55], p < 0.001, k = 6). Six months post treatment, pain (SMD = -1.31 [95 %-CI: -2.25, -0.38], p = 0.006, k = 5), synovial hypertrophy (SMD = -0.50 [95 %-CI: -0.65, -0.36], p < 0.001, k = 4), and orthopaedic joint score (SMD = -0.61 [95 %-CI: -0.92, -0.30], p < 0.001, k = 4) showed moderate to large improvements. Average RoM changes were minimal (2.6 % improvement). The overall complication rate was 12 per 1000 treated joints. CONCLUSION: Despite promising results, the overall quality of evidence was moderate to low due to high methodological heterogeneity and lack of control groups. These findings suggest RSO is a safe and effective treatment for key clinical outcomes in PwH, but further well-designed controlled trials are needed to confirm these results.
OBJECTIVE: Systems employing point-of-care (POC) INR monitoring with patient self-testing require test accuracy, data integrity, patient compliance, and prompt two-way communication for high quality warfarin management....OBJECTIVE: Systems employing point-of-care (POC) INR monitoring with patient self-testing require test accuracy, data integrity, patient compliance, and prompt two-way communication for high quality warfarin management. With a goal of validating a POC Bluetooth capable device for prompt INR transfer to electronic medical record, two POC INR devices were compared against an internal plasma INR reference. METHODS: A multicenter study (February 14, 2023 - August 29, 2023) comparing concordance of two commercially available POC devices, Vantus and CoaguChek XS (Pro and Plus), against a plasma INR reference, was pursued among warfarin treated patients. Appropriateness of dosing decisions were assessed for each device. RESULTS: Across three Mayo Clinic sites, 151 warfarin treated patients agreed to participate. Atrial fibrillation (41.7 %), venous thromboembolism (33.1 %) and heart valve prosthesis (19.9 %) were common indications with target INR range 2.0-3.0 in 89 %. For the CoaguChek devices, 86.1 % of values fell within 0.4 INR units compared with plasma INR referent (CoaguChek - plasma INR correlation R = 0.95). For the Vantus device, 88.7 % of values fell within 0.4 INR units of plasma INR values (Vantus - plasma INR correlation R = 0.96). Mean (± standard deviation) deviation from plasma INR was 0.2 ± 0.3 for CoaguChek compared to 0.1 ± 0.2 for Vantus (p < 0.001). Using the plasma INR as the gold standard for dosing recommendations, appropriate dosing recommendations were similar between devices: CoaguChek 83.4 % vs Vantus 82.7 %. CONCLUSIONS: Compared to a plasma referent, INR values obtained from the CoaguChek and Vantus devices exhibited strong correlation with plasma INR values without systemic bias.
Hemostasis is a complex physiological process that prevents blood loss following vascular injury via the blood coagulation cascade. The coagulation cascade is a highly controlled stepwise process that establishes clottin...Hemostasis is a complex physiological process that prevents blood loss following vascular injury via the blood coagulation cascade. The coagulation cascade is a highly controlled stepwise process that establishes clotting only at the site of bleeding, when needed. Recently, aptamers have been employed not only in the fields of biosensors and diagnostics, but also in molecular imaging, therapeutics, and drug delivery systems. The present article highlights recent developments in aptamer-based biomedical systems for the diagnosis and treatment of blood coagulation cascade disorders. Specifically, aptasensors for thrombin detection and aptamer-based medical imaging of thrombi were addressed as diagnostic tools for coagulation cascade disorders. Additionally, the use of aptamers as pharmaceutical agents and aptamer-targeted drug delivery systems were highlighted as part of the treatment. In summary, this is a valuable compilation in this emerging field that focuses on aptamer-based applications for monitoring and treatment of blood coagulation cascade disorders.
BACKGROUND: Thrombosis, encompassing both venous thromboembolism (VTE) and arterial thrombotic events, represents a leading cause of mortality in patients with Systemic Lupus Erythematosus (SLE). A comprehensive evaluati...BACKGROUND: Thrombosis, encompassing both venous thromboembolism (VTE) and arterial thrombotic events, represents a leading cause of mortality in patients with Systemic Lupus Erythematosus (SLE). A comprehensive evaluation of risk factors specific to each thrombotic type remains lacking. OBJECTIVE: To systematically identify and compare risk factors for venous and arterial thrombosis in SLE patients through a meta-analysis. METHODS: We systematically searched PubMed, Web of Science, Embase, Cochrane Library, CNKI, and Wanfang Data from inception to August 2025. Cohort studies (prospective or retrospective) and case-control studies reporting multivariable-adjusted associations between risk factors and thrombotic events in SLE were included. Two researchers independently performed study selection, data extraction, and quality assessment using the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated using random-effects models. RESULTS: Analysis of 25 studies (13,290 patients) identified distinct risk factor profiles. For venous thrombosis, lupus anticoagulant showed the strongest association (OR 6.17, 95 % CI 2.77-13.76), followed by anti-β2-glycoprotein I IgA (OR 4.77, 95 % CI 3.08-7.39). Antiphospholipid syndrome demonstrated an exceptionally high risk (OR 44.72, 95 % CI 9.93-201.34). Elevated D-dimer was a specific venous thrombosis predictor (OR 1.35, 95 % CI 1.22-1.49). For arterial thrombosis, traditional cardiovascular risk factors predominated, including hypertension (OR 3.39, 95 % CI 2.38-4.83) and obesity (OR 3.17, 95 % CI 1.50-6.66). Disease-related factors such as high SLEDAI scores (OR 1.11, 95 % CI 1.05-1.16) and renal insufficiency (OR 2.38, 95 % CI 1.42-4.00) were associated with increased thrombotic risk. CONCLUSION: Thrombosis in SLE exhibits distinct risk factor patterns between venous and arterial events. Venous thrombosis is strongly driven by antiphospholipid antibodies, while arterial events are predominantly associated with traditional cardiovascular risk factors. This review identifies and distinguishes key risk factors for venous and arterial thrombosis in SLE. These findings highlight the necessity for thrombotic type-specific risk assessment and provide an evidence base to inform the future development of targeted preventive strategies.
BACKGROUND: The clinical utility of routine thrombophilia testing to guide management in pediatric venous thromboembolism (VTE) is debated. This study sought to evaluate the real-world impact of thrombophilia testing on...BACKGROUND: The clinical utility of routine thrombophilia testing to guide management in pediatric venous thromboembolism (VTE) is debated. This study sought to evaluate the real-world impact of thrombophilia testing on anticoagulation duration and clinical outcomes. METHODS: We conducted a 10-year retrospective cohort study of 67 pediatric patients with VTE. We analyzed the association between thrombophilia status and anticoagulation duration, VTE recurrence, and thrombus resolution on follow-up imaging. RESULTS: The majority of VTE events (80.6 %) were provoked. A positive thrombophilia workup did not significantly alter the median anticoagulation duration compared to a negative workup (p = 0.582). A positive thrombophilia status was not a significant predictor of VTE recurrence in survival analysis (HR 2.22, p = 0.281). However, a positive workup was significantly associated with a higher rate of Residual Vein Obstruction (RVO) (73.3 % vs. 36.4 %, p = 0.045). This imaging finding did not, in turn, predict VTE recurrence (p = 0.388). CONCLUSION: Thrombophilia testing did not influence treatment duration or predict recurrence. Our findings provide real-world evidence supporting current guidelines that advocate for a selective, clinically driven approach to testing rather than its routine use after a first pediatric VTE.
BACKGROUND: The indications for anticoagulation and the number of patients on anticoagulation is rising. Accordingly, adverse drug events related to anticoagulation use are on the rise and represents an opportunity for i...BACKGROUND: The indications for anticoagulation and the number of patients on anticoagulation is rising. Accordingly, adverse drug events related to anticoagulation use are on the rise and represents an opportunity for improvement in patient safety. About 15-20 % of patients on anticoagulation undergo invasive procedures. Perioperative management of anticoagulation requires balancing competing risks of thrombosis and bleeding. Clear, concise and evidence-based institutional guidelines are essential for providers to make individualized treatment decisions and to improve patient safety. STUDY DESIGN AND METHODS: We qualitatively compared perioperative anticoagulation management guidelines from 11 US academic institutions. We also conducted a survey to evaluate how healthcare providers interpret perioperative anticoagulation management when different wording is used to convey recommendations. RESULTS: Institution-specific guidelines of the 11 US academic institutions varied in the management of perioperative anticoagulation and used different language to convey recommendations. In the survey, there was >90 % consensus amongst healthcare providers on the appropriate management of perioperative rivaroxaban and apixaban when the guidelines used the wording of "no dose day -X" which is used in the American College of Chest Physicians (CHEST) 2022 guidelines. Additionally, institution-specific guidelines were not available in 24.2 % of survey respondents. CONCLUSIONS: This study demonstrates that institutions do not always have perioperative guidelines for anticoagulation management and when they do, there is variation in recommendations despite published international guidelines for perioperative management of anticoagulation. The language used to convey recommendations is important to standardizing perioperative anticoagulation management. These represent areas for further quality improvement and patient safety through anticoagulation stewardship.
Non-syndromic inherited brain arteriovenous malformation (bAVM) is a very rare condition whose molecular basis is still uncharacterized. In contrast, sporadic bAVM can arise following gain-of-function mutations in the KR...Non-syndromic inherited brain arteriovenous malformation (bAVM) is a very rare condition whose molecular basis is still uncharacterized. In contrast, sporadic bAVM can arise following gain-of-function mutations in the KRAS and BRAF proto-oncogenes. The bAVM lesion is characterized by a direct arteriole-to-venule shunt and the absence of a normal capillary bed, due to impaired expression of endothelial differentiation markers and failed arterial specification. In this context, perturbation of EphrinB2-EphB4 reverse signaling plays a pivotal role. According to this knowledge, this study describes the possible role of the PTPN13 gene in non-syndromic inherited bAVM. Whole-exome sequencing was performed on germline DNA purified from peripheral blood of two consanguineous relatives affected by bAVM. Common rare genetic variants were selected and affected genes were prioritized. RNA-sequencing was conducted on endothelial cells isolated from the bAVM lesion after surgical removal. Differentially expressed genes were functionally clustered. The resulting data were integrated to determine the possible common genetic cause of the phenotype in both relatives. PTPN13 was identified as a possible causative gene for non-syndromic inherited bAVM. By dephosphorylating EphrinB2 and SRC in particular, it contributes to the modulation of the EphrinB2- EphB4 reverse signaling, during arterial specification. Moreover, this phenotype does not depend on KRAS and BRAF gain-of-function, in contrast to the sporadic form. Given the exceptional nature of the non-syndromic inherited phenotype, this study represents the first evidence of a candidate gene for this rare form of the disease, further suggesting a novel field of investigation for the bAVM pathogenesis.
Koskinen M, Ruotsalainen E, Wallin M
… +7 more, Kivelä H, Carlsson K, Petäjä J, Hirvensalo E, Mäkijärvi M, Lassila R, Outpatient LMWH-Covid-19 Study Group
BACKGROUND: Covid-19 and venous thromboembolism (VTE) share risk factors and thrombo-inflammatory pathophysiology. In-hospital low-molecular-weight heparin (LMWH) use improved outcomes. Before vaccinations or available t...BACKGROUND: Covid-19 and venous thromboembolism (VTE) share risk factors and thrombo-inflammatory pathophysiology. In-hospital low-molecular-weight heparin (LMWH) use improved outcomes. Before vaccinations or available treatments, the Helsinki university hospital in Finland, initiated LMWH thromboprophylaxis to Covid-19 outpatients with progressing illness and high-risk of VTE (LMWH+ group), aligning with the existing in-hospital guidance for thromboprophylaxis. METHODS: We observationally studied whether pre-admission LMWH thromboprophylaxis impacted outcomes: hospital and ICU stay, and respiratory support after Covid-19 hospitalization. We compared control group (LMWH-) by propensity score-matching comorbidities, medications and Covid-19 severity and VTE risk with the LMWH+ group with 30-day follow-up. RESULTS: Among 1189 hospitalized patients, 241 were stratified in the LMWH+ group and 482 were propensity-matched into the LMWH- group. The mean time (±SD) from Covid-19 diagnosis until outpatient thromboprophylaxis in the LMWH+ group was 1.9 (±3.0) days; ~80 % of patients received thromboprophylaxis ≤2 days after the diagnosis. Longer duration of pre-admission LMWH use was associated with shorter hospital stays and less days with respiratory support (p < 0.006-0.008). The incidences of bleeds and VTE (LMWH+ 4.6 %, LMWH- 5.4 %) were similar. Overall, 2.9-fold higher mortality (p = 0.014) occurred in the LMWH- (10.6 %) versus the LMWH+ group (3.7 %). CONCLUSIONS: Outpatient LMWH given pre-admission for high-risk Covid-19 patients was associated with improved outcome following diagnosis: shorter respiratory support and hospital stay with reduced need for intensive care. Our findings support early initiation of LMWH in risk-stratified patients to manage thrombo-inflammation. While being Covid-19 aftermath, our study is relevant for any other severe viral outbursts associated with thrombogenicity.
BACKGROUND: Abdominal sepsis frequently leads to disseminated intravascular coagulation (DIC), exacerbating organ dysfunction and bleeding complications. Although anticoagulant therapy is a potential treatment for DIC, i...BACKGROUND: Abdominal sepsis frequently leads to disseminated intravascular coagulation (DIC), exacerbating organ dysfunction and bleeding complications. Although anticoagulant therapy is a potential treatment for DIC, its use in this context raises concerns about bleeding risks. OBJECTIVES: The purpose of this study is to investigate the risks and benefits of DIC-targeted anticoagulant therapy in patients with abdominal sepsis. METHODS: Data were analyzed from a dataset from a multicenter nationwide retrospective cohort study (J-Septic DIC registry) in Japan between 2011 and 2013. The study included 987 patients with abdominal sepsis-induced DIC, diagnosed within three days of ICU admission. Patients were divided into DIC-targeted anticoagulant therapy (recombinant thrombomodulin or antithrombin) and non-use groups. Propensity score matching was used to adjust for confounding factors. The primary outcome was all-cause 90-day mortality, with bleeding complications requiring blood transfusion as the primary safety outcome. RESULTS: The results indicated that anticoagulant therapy was associated with improved survival (hazard ratio: 0.662, 95 % confidential interval: 0.472-0.929), but a higher risk of bleeding complications (OR: 2.451, 95 % confidential interval:1.372-4.379). Dual combination of anticoagulant therapy did not provide additional survival benefits and increased bleeding risks. The efficacy of DIC-targeted anticoagulant therapy correlated with disease severity, while bleeding risk was inversely correlated with severity. CONCLUSION: DIC-targeted anticoagulant therapy in patients with abdominal sepsis was related with improved prognosis but increased bleeding risks. The risk-benefit profile varies with disease severity, suggesting a need for cautious and personalized treatment strategies.
BACKGROUND: Effective anticoagulant therapies are crucial for managing thrombotic disorders, especially in children. While currently available direct oral anticoagulants offer many advantages over current standard of car...BACKGROUND: Effective anticoagulant therapies are crucial for managing thrombotic disorders, especially in children. While currently available direct oral anticoagulants offer many advantages over current standard of care anticoagulants, including predictable pharmacokinetics and reduced need for monitoring, they still have significant bleeding risks. Milvexian, a direct factor XIa inhibitor, has demonstrated potential in reducing bleeding risks compared to traditional anticoagulants and warrants further investigation in neonates and children. OBJECTIVES: This study aimed to investigate the age-related anticoagulant effect of milvexian in vitro. PATIENTS/METHODS: Plasma samples from healthy participants from the following age groups: neonates, 28 days-23 months, 2-6 years, 7-11 years, 12-18 years, and adults were spiked with increasing concentrations of milvexian (0.1, 1.0, 3.0 and 10 μM). Clotting time was measured using an activated partial thromboplastin time (aPTT) assay, and thrombin generation parameters were assessed. RESULTS: A dose-dependent increase in clotting time was observed across all age groups. Thrombin generation parameters, including Lag time and time to peak (ttPeak), showed a linear dose-dependent increase, while endogenous thrombin potential (ETP), Peak, and Velocity index decreased dose-dependently. Significant age-specific differences were noted primarily in neonates and children less than two years of age compared to adults. CONCLUSION: In vitro findings indicate a predictable, linear dose-response to milvexian, with significant in vitro anticoagulant effect differences in neonates and children under two years of age. Further in vivo studies are required to confirm these findings, determine dosing strategies, and assess clinical implications in the paediatric population.
BACKGROUND: Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) are commonly used for the diagnosis of portal vein thrombosis (PVT), however, their accuracy compared to invasive tests is...BACKGROUND: Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) are commonly used for the diagnosis of portal vein thrombosis (PVT), however, their accuracy compared to invasive tests is not clearly known. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central, and Scopus databases for studies assessing the sensitivity and specificity of US, CT, and MRI for PVT diagnosis. Inclusion criteria required at least 10 participants and comparison with invasive gold standards (angiography or surgery/pathology). The quality assessment was performed using the QUADAS-2 tool. Pooled estimates of sensitivity and specificity were calculated through mixed-effects logistic regression model and reported with 95 % confidence intervals (CI). Based on the obtained results, we computed Bayesian models simulating the work-up of PVT in case of different clinical pre-test probabilities of PVT. RESULTS: Out of 8526 identified citations, 26 studies with 1499 patients were included in the meta-analysis. The risk of bias was low in 3 studies. Pooled sensitivities and specificities were 0.84 (95 %CI 0.69-0.92) and 0.96 (95 %CI 0.92-0.98) for US, 0.81 (95 %CI 0.66-0.90) and 0.96 (95 %CI 0.88-0.99) for CT, and 0.81 (95 %CI 0.65-0.90) and 0.98 (95 %CI 0.96-0.99) for MRI. In patients with a pre-test probability of PVT of 30 %, a positive US yields a post-test probability of PVT of 90 % and a second positive imaging result leads to a post-test probability of 99 %. CONCLUSIONS: US, CT, and MRI demonstrate comparable accuracy for PVT diagnosis, with a high specificity across modalities. A stepwise diagnostic approach integrating clinical probability and imaging results could optimize diagnostic confidence.