Robert Bizaleri Baluku, Faith Ameda, Eva Nabawanuka, Christine Sekaggya-Wiltshire
{"title":"High incidence of undiagnosed deep vein thrombosis among hospitalized people living with HIV: a cross-sectional study.","authors":"Robert Bizaleri Baluku, Faith Ameda, Eva Nabawanuka, Christine Sekaggya-Wiltshire","doi":"10.1186/s12959-025-00743-7","DOIUrl":"10.1186/s12959-025-00743-7","url":null,"abstract":"<p><strong>Background: </strong>Deep venous thrombosis (DVT) is part of a spectrum of venous thromboembolism, which also includes pulmonary embolism. Up to 50% of hospitalized individuals who develop pulmonary embolism have DVT. Pulmonary embolism is responsible for up to 10% of hospital deaths. However, the burden and specific risk factors for DVT among inpatients living with HIV in our setting are not well established. Thromboprophylaxis, which reduces the risk of DVT, is not routinely administered to all inpatients. Understanding the burden and risk factors for DVT in this population can guide the implementation of preventive measures, identify high-risk individuals, and inform guidelines for thromboprophylaxis.</p><p><strong>Methods: </strong>This cross-sectional study was conducted between October 2023 and April 2024 in two National Referral hospitals among hospitalized people living with HIV. A total of 186 participants were consecutively sampled and enrolled in the study. All adult inpatients living with HIV who fulfilled the eligibility criteria had a bedside Doppler ultrasound scan of the lower limbs for DVT. Relevant demographic, clinical, laboratory, and HIV-related data were obtained. Both bivariable and multivariable analyses were performed via R software.</p><p><strong>Results: </strong>Up to 186 participants were enrolled, with a median age of 40 years (interquartile range (IQR): 34-52). The prevalence of lower limb DVT was 18.3% (34/186). The participants with DVT had a median age of 49 years (IQR: 39-56, p-value 0.045). Up to 53% (99/186) of the participants were male. The median duration of hospitalization was 5.0 days (IQR: 4.0-7.8) among those with DVT. A positive history of cigarette smoking was identified in 6.5% (12/34) of the participants and was significantly associated with the development of DVT (P-value = 0.004). TB coinfection was significantly associated with DVT, with a prevalence ratio (PR) of 2.22 (P-value = 0.007). A low CD4 (< 200) was also significantly associated with lower limb DVT (PR = 2.70, P-value = 0.003).</p><p><strong>Conclusion: </strong>The prevalence of lower limb DVT among hospitalized people living with HIV is high (18.3%) in our setting. Older age, a positive history of smoking, a low CD4 count (< 200), and TB coinfection are significant risk factors for DVT in HIV-positive inpatients.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"53"},"PeriodicalIF":2.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiacheng Zhang, Nan Wang, Tianyou Xin, Xiaojun Zhu, Shengkun Lang, Xin Ge
{"title":"Liquiritin mitigates lower extremity deep vein thrombosis by inhibiting inflammation and oxidative stress via the NF-κB signaling pathway.","authors":"Jiacheng Zhang, Nan Wang, Tianyou Xin, Xiaojun Zhu, Shengkun Lang, Xin Ge","doi":"10.1186/s12959-025-00739-3","DOIUrl":"10.1186/s12959-025-00739-3","url":null,"abstract":"<p><strong>Background: </strong>Lower extremity deep vein thrombosis (LEDVT) is a common vascular disease, with its pathogenesis mainly involving inflammatory responses and oxidative stress. Liquiritin (LIQ) is a flavonoid that exhibits pharmacological effects such as anti-inflammatory and antioxidant properties. This study aimed to investigate the role of LIQ in LEDVT and its potential mechanisms.</p><p><strong>Methods: </strong>We established an LEDVT model in mice by ligating the inferior vena cava (IVC) and performed in vitro experiments by stimulating human umbilical vein endothelial cells (HUVECs) with IL-1β (10 ng/mL) to simulate endothelial cell injury.</p><p><strong>Results: </strong>We found that LIQ significantly reduced the size and weight of thrombi and decreased the concentrations of inflammatory factors TNF-α and IL-6 in the IVC of LEDVT mice. Furthermore, LIQ inhibited the secretion of prothrombotic mediators such as tissue factor (TF) and vascular cell adhesion molecule-1 (VCAM-1). Administration of LIQ resulted in a notable reduction in immune inflammatory cells in the IVC of LEDVT mice. LIQ also demonstrated antioxidant properties, as the treatment of LIQ enhanced SOD activity and restored ROS levels to normal in the IVC. Similarly, LIQ reduced the formation of inflammatory factors and the secretion of prothrombotic mediators by HUVECs while inhibiting oxidative stress in HUVECs. Finally, LIQ effectively suppressed the levels of phosphorylated p65 in both the IVC and HUVECs.</p><p><strong>Conclusions: </strong>LIQ reduces inflammatory responses and oxidative stress in LEDVT by inhibiting the NF-κB signaling pathway. This finding provides new insights into the prevention and treatment of LEDVT.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"51"},"PeriodicalIF":2.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential drug targets for peripheral artery disease identified through Mendelian randomization analysis.","authors":"Xu Ding, Hui Li, Lihong Li, Yongjiu Yang, Zhong Chen","doi":"10.1186/s12959-025-00738-4","DOIUrl":"10.1186/s12959-025-00738-4","url":null,"abstract":"<p><strong>Introduction: </strong>Peripheral Artery Disease (PAD) is a common cardiovascular condition marked by peripheral artery stenosis or occlusion. Despite treatment advancements, patients will still face vascular complications, highlighting the need for innovative therapies. Human proteins play crucial roles in biology and drug research. Mendelian randomization (MR) analysis, a gene-based method, is increasingly used in drug target identification. This study aims to identify PAD-associated plasma proteins through MR analysis for potential therapies.</p><p><strong>Methods: </strong>We first used GWAS data and seven pQTL datasets to identify plasma proteins causally linked to PAD through MR analysis. Then, we performed KEGG pathway enrichment analysis, Bayesian colocalization analysis, and MR-BMA analysis were carried out to investigate mechanisms and prioritize these proteins. Finally, we assessed the druggability of the target proteins using the DrugBank database.</p><p><strong>Results: </strong>MR analysis found four plasma proteins causally linked to PAD: MMP3 positively correlated with PAD, while CASS4, ISG15, and MMP1 exhibited negative associations. Bayesian colocalization analysis confirmed these relationships, and the MR-BMA analysis prioritized MMP1 as the main target. KEGG pathway enrichment analysis highlighted lipid metabolism and atherosclerosis pathways as central to these drug targets. The druggability evaluation indicated that drugs targeting these proteins are either in development or already in clinical use.</p><p><strong>Conclusion: </strong>This study integrates genetic and proteomic data to identify therapeutic targets for PAD and evaluate their potential for drug development. The prioritization of MMP1 and ISG15 as key targets shows promise for PAD treatment, but further validation and clinical exploration of these findings are needed.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"52"},"PeriodicalIF":2.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune thrombotic thrombocytopenic purpura and diabetic ketoacidosis: a case report and literature review.","authors":"Geng-Hao Bai, Mei-Hwa Lin, Yu-Pei Chen, Tien-Jyun Chang, Sheng-Chieh Chou","doi":"10.1186/s12959-025-00740-w","DOIUrl":"10.1186/s12959-025-00740-w","url":null,"abstract":"<p><strong>Background: </strong>Thrombotic thrombocytopenic purpura (TTP) is an uncommon and life-threatening disorder caused by a deficiency of ADAMTS-13, and eventually leads to microangiopathic hemolytic anemia, severe thrombocytopenia, and organ damages. Acute TTP events could be triggered by infections, or inflammations in the context of ADAMTS-13 deficiency. Recently, several case reports have indicated an association between diabetic ketoacidosis (DKA) and TTP. Here, we present a case with the concomitant presentation of DKA and TTP.</p><p><strong>Case presentation: </strong>A 37-year-old male with diabetes mellitus presented with typical symptoms of diabetic ketoacidosis. He was managed with an insulin pump and intravenous fluids. However, he developed seizure and progressed to coma, his rapidly deteriorating condition necessitated continuous renal replacement therapy, intubation, and inotropic support. Laboratory data indicated hemolytic anemia and thrombocytopenia, and a blood smear revealed schistocytes. The PLASMIC score was 5, and ADAMTS-13 activity was 2%. The patient was diagnosed with TTP and treated with therapeutic plasma exchange, steroids, and rituximab. His platelet count stabilized above 150,000/µL, and ADAMTS-13 activity progressively improved.</p><p><strong>Conclusions: </strong>This case report emphasizes the concurrence of DKA and iTTP, presenting the rare complication of acute renal failure in TTP. TTP is a rare and serious disease that requires prompt recognition and management. Concurrent conditions should be considered when calculating prediction scores such as the PLASMIC and French scores.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"50"},"PeriodicalIF":2.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anthony J Weekes, Fernanda Calienescerpa, Kelly L Goonan, Alexa L Polzella, Melanie M Hogg, Dalton Cox, Sean Flannigan, Emma Cruz, Halie A O'Neill, Nathaniel S O'Connell, Daniel R Troha
{"title":"Association of initial national early warning score with clinical deterioration in pulmonary embolism.","authors":"Anthony J Weekes, Fernanda Calienescerpa, Kelly L Goonan, Alexa L Polzella, Melanie M Hogg, Dalton Cox, Sean Flannigan, Emma Cruz, Halie A O'Neill, Nathaniel S O'Connell, Daniel R Troha","doi":"10.1186/s12959-025-00735-7","DOIUrl":"10.1186/s12959-025-00735-7","url":null,"abstract":"<p><strong>Background: </strong>The National Early Warning Score (NEWS2) predicts clinical deterioration in hospitalized patients. Its role in pulmonary embolism (PE) risk stratification remains underexplored. This study assessed the association of initial NEWS2 with clinical deterioration and advanced interventions during hospitalization.</p><p><strong>Methods: </strong>We retrospectively analyzed a PE response team (PERT) registry of adults with submassive and massive PE from 11 emergency departments (2016-2024). Initial NEWS2 was calculated for each registry patient. The primary outcome was in-hospital PE-related clinical deterioration (death, cardiac arrest, vasoactive medications for hypotension, or emergent respiratory interventions). The secondary outcome was advanced intervention use. We calculated odds ratios (OR) for different NEWS2 cut-offs. We used multivariable analysis to assess the association of NEWS2 and study outcomes, and decision curve analysis to determine net benefit of clinical deterioration.</p><p><strong>Results: </strong>Among 2119 patients (mean age 62.2 [16.8], 51.2% female, 168 [7.9%] with massive PE, and 1951 [92.1%] with submassive PE), 309 patients (14.6%) experienced clinical deterioration and 488 (23.0%) required advanced interventions. Mean NEWS2 was higher in patients with vs. without clinical deterioration (6.0 ± 3.3 vs. 3.0 ± 2.4; p < 0.001) and in those with vs. without advanced interventions (4.8 ± 3.1 vs. 3.0 ± 2.5; p < 0.001). NEWS2 cut-off of ≥ 3 identified patients at risk of clinical deterioration: sensitivity 87% (82-90%), OR 6.1 (95% CI: 4.3-8.5), and negative predictive value (NPV) 96% (94-97%). NEWS2 cut-off ≥ 4 had specificity of 62% (60-65%), OR of 5.1 (95% CI: 3.9-6.7), and NPV of 94% (92-95%). As a continuous variable, NEWS2 had an OR of 1.2 (95% CI: 1.1-1.3). NEWS2 cut-offs from 3 to 5 showed an improved net benefit (0.08, 0.16, and 0.34) compared with treating all patients as high risk for clinical deterioration.</p><p><strong>Conclusion: </strong>Patients with PE and initial NEWS2 scores ≥ 3 had a four-fold to eight-fold higher odds of clinical deterioration than those with NEWS2 < 3. NEWS2 is useful for predicting clinical deterioration and guiding intervention strategies in PE.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"49"},"PeriodicalIF":2.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rong Zhang, Xiao Mei Wang, Chao Yun Jiang, Tian Hong Cai, Jian Feng He, Kai Chen, Dian Xi Chen, Teng Hui Zhan
{"title":"A retrospective cohort analysis of plasma TAT level trends and adverse pregnancy outcomes in early pregnancy patients with newly diagnosed VTE.","authors":"Rong Zhang, Xiao Mei Wang, Chao Yun Jiang, Tian Hong Cai, Jian Feng He, Kai Chen, Dian Xi Chen, Teng Hui Zhan","doi":"10.1186/s12959-025-00732-w","DOIUrl":"10.1186/s12959-025-00732-w","url":null,"abstract":"<p><strong>Objective: </strong>Venous thromboembolism (VTE) is a leading cause of maternal mortality, yet effective biomarkers for early prediction of adverse pregnancy outcomes remain limited. We aimed to investigate the association between changes in thrombin-antithrombin complex (TAT) levels and adverse pregnancy outcomes in early-pregnancy patients with VTE.</p><p><strong>Methods: </strong>In this retrospective cohort study, we enrolled 89 pregnant women diagnosed with VTE during early pregnancy (< 14 weeks) who received care at Fujian Maternity and Child Health Hospital between June 2021 and May 2024. Plasma TAT levels measured in early and mid-pregnancy were collected as exposure variables, while adverse pregnancy outcomes (including miscarriage, preterm birth, and fetal growth restriction) served as outcome variables. Multivariate regression analysis was performed to evaluate the association between TAT level changes and adverse pregnancy outcomes, adjusting for potential confounding factors including age, BMI, and obstetric history. Additionally, threshold effect analysis was conducted.</p><p><strong>Results: </strong>After adjusting for potential confounding factors including age, BMI, and underlying conditions, changes in TAT levels were significantly associated with a reduced risk of adverse pregnancy outcomes (adjusted OR = 0.62, 95% CI: 0.47-0.80). Threshold effect analysis identified a critical turning point of -2.87 in TAT level changes (TATp2-1), below which the risk of adverse outcomes increased significantly (adjusted OR = 0.37, 95% CI: 0.22-0.63).</p><p><strong>Conclusion: </strong>The association between TATp2-1 and adverse pregnancy outcomes in early pregnancy VTE patients was non-linear. A threshold effect was observed with an inflection point of -2.87. When the TATp2-1 were below - 2.87, there was a significantly increased risk of adverse pregnancy outcomes.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"48"},"PeriodicalIF":2.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoteng Ma, Huijun Chu, Yan Sun, Yujing Cheng, Dai Zhang, Lixia Yang, Zhijian Wang, Xiaoli Liu, Yujie Zhou
{"title":"Prognostic significance of stress hyperglycemia ratio in patients with type 2 diabetes mellitus and acute coronary syndromes.","authors":"Xiaoteng Ma, Huijun Chu, Yan Sun, Yujing Cheng, Dai Zhang, Lixia Yang, Zhijian Wang, Xiaoli Liu, Yujie Zhou","doi":"10.1186/s12959-025-00729-5","DOIUrl":"10.1186/s12959-025-00729-5","url":null,"abstract":"<p><strong>Background: </strong>Prognostic significance of stress hyperglycemia ratio (SHR) has not been well studied in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndromes (ACS).</p><p><strong>Methods: </strong>We prospectively measured admission fasting blood glucose (AFBG) and glycated hemoglobin A1c (HbA1c), and retrospectively calculated the stress hyperglycemia ratio (SHR, = AFBG/[1.59 × HbA1c (%) - 2.59]) in 791 patients with T2DM and ACS undergoing percutaneous coronary intervention (PCI). The primary endpoint was defined as major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, and unplanned repeat coronary revascularization.</p><p><strong>Results: </strong>The mean age of the study population was 61 ± 10 years, and 72.8% were male. Over a median follow-up of 927 days, 194 patients developed at least one primary endpoint event. The follow-up incidence of MACCE increased in parallel with SHR tertiles (15.6%, 21.9%, and 36.1%, respectively; P for trend < 0.001). The Cox proportional hazards regression analysis adjusted for multiple confounding factors showed hazard ratios for MACCE of 1.525 (95% CI: 1.009-2.305; P = 0.045) for the middle tertile and 2.525 (95% CI: 1.729-3.687; P < 0.001) for the highest tertile of SHR, with the lowest tertile as the reference. The addition of SHR to the baseline reference prediction model improved model predictive performance markedly (C-statistic: increased from 0.704 to 0.721; cNRI: 0.176 [95% CI: 0.063-0.282], P = 0.002; IDI: 0.030 [95% CI: 0.009-0.063], P = 0.002).</p><p><strong>Conclusion: </strong>SHR was independently and significantly associated with adverse cardiovascular outcomes in T2DM and ACS patients who underwent PCI, and had an incremental effect on the predictive ability of the baseline reference prediction model.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"47"},"PeriodicalIF":2.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"D-dimer to fibrinogen ratio as a marker for acute cerebral venous thrombosis.","authors":"Minh-Hoang Tran, Kim-Huong Truong-Nguyen","doi":"10.1186/s12959-025-00730-y","DOIUrl":"https://doi.org/10.1186/s12959-025-00730-y","url":null,"abstract":"<p><p>Despite D-dimer to fibrinogen ratio (DFR) being reported as a prognostic factor for cerebral venous thrombosis (CVT), we note some concerns about the misused terminology (prognostic versus predictive), potential variability in D-dimer and fibrinogen assays that may impact the reliability and utility of DFR. From the statistical aspect, its validity was not adequately ensured due to inappropriate methods (inability to address multicollinearity, confounding, and multiple comparisons) and lack of validation for unvalidated discrimination cut-offs. The prognostic value of DFR was not clinically or statistically justified, given its poor-to-acceptable discrimination. Finally, an unexpectedly positive association between venous cerebral infarction and non-severe CVT suggests possible issues in data labelling, reference value, uncontrolled confounders/biases, or overadjustment. Addressing these issues would strengthen the reliability, validity, and utility of DFR in CVT prognosis.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"46"},"PeriodicalIF":2.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaofeng Yan, Yishan Lu, Keyu Lv, Miao Jiang, Chao Fang, Yi Wu, Aizhen Yang
{"title":"Endoplasmic reticulum protein 29 negatively regulates platelet functions and thrombosis in mice.","authors":"Xiaofeng Yan, Yishan Lu, Keyu Lv, Miao Jiang, Chao Fang, Yi Wu, Aizhen Yang","doi":"10.1186/s12959-025-00726-8","DOIUrl":"https://doi.org/10.1186/s12959-025-00726-8","url":null,"abstract":"<p><strong>Background: </strong>Several members of protein disulfide isomerase (PDI) family with the CXYC active motif such as PDI, ERp57, ERp72, ERp46, ERp5 and TMX1 have important roles in platelet functions and thrombosis. These members contribute to the network of redox regulation of platelet activities. However, whether other PDI family members without the CXYC motif such as ERp29, have a role in these processes remains unknown.</p><p><strong>Aims: </strong>To determine the role of ERp29 in platelet functions and thrombosis.</p><p><strong>Methods: </strong>The phenotypes of platelet-specific ERp29-deficient (Pf4-Cre/ERp29<sup>fl/fl</sup>) mice were evaluated using tail bleeding assay and laser-induced and FeCl<sub>3</sub>-induced arterial injury models, as well as venous thrombosis model. In vitro, the functions of ERp29-deficient platelets were assessed in respect to aggregation, adhesion, spreading, clot retraction, granule secretion and integrin αIIbβ3 activation measured by flow cytometry. Redox state of integrin αIIbβ3 thiols was detected using 3-(N-maleimido-propionyl) biotin (MPB) labeling.</p><p><strong>Results: </strong>Compared with WT mice, Pf4-Cre/ERp29<sup>fl/fl</sup> mice exhibited shortened tail-bleeding times, increased platelet accumulation in the two arterial thrombosis models, and enhanced thrombogenesis in the venous thrombosis model. ERp29-deficient platelets had enhanced response in aggregation, ATP release, spreading, clot retraction, αIIbβ3 activation, fibrinogen binding and P-selectin expression. As detected by MPB labeling, the free thiol content of integrin αIIbβ3 in ERp29-deficient platelets were increased compared with WT platelets, suggesting that the role of ERp29 is associated with oxidation of the functional disulfides of integrin αIIb and/or β3 subunits.</p><p><strong>Conclusion(s): </strong>ERp29 is the first disulfide isomerase without the CXYC motif that negatively regulates platelet function. This study provides new insight into the redox network controlling thrombosis.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"44"},"PeriodicalIF":2.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salam Ibrahim Abou Safrah, Mohamed Omar Saad, May Alasmar, Fatima Ashfaq Butt, Somaya Khaled Koraysh
{"title":"Enoxaparin dosing for venous thromboembolism prophylaxis in hospitalized underweight adult patients: a retrospective cohort study.","authors":"Salam Ibrahim Abou Safrah, Mohamed Omar Saad, May Alasmar, Fatima Ashfaq Butt, Somaya Khaled Koraysh","doi":"10.1186/s12959-025-00716-w","DOIUrl":"https://doi.org/10.1186/s12959-025-00716-w","url":null,"abstract":"<p><strong>Background: </strong>Enoxaparin is commonly used for venous thromboembolism (VTE) prophylaxis in adult hospitalized patients. Although anti-Xa levels are inversely related to body weight, limited studies evaluated clinical outcomes of dose reduction in the underweight population.</p><p><strong>Objective: </strong>To compare the incidence of bleeding and VTE in underweight patients receiving reduced doses of enoxaparin (< 40 mg daily) versus the standard dose (40 mg daily) for VTE prophylaxis.</p><p><strong>Methods: </strong>This was a multicentre retrospective cohort study at Hamad Medical Corporation in Qatar. We included hospitalized patients with a total body weight ≤ 57 kg or body mass index (BMI) ≤ 18.5 kg/m<sup>2</sup> who received prophylactic enoxaparin for at least 48 h. The outcomes were bleeding, VTE, and composite unfavourable outcome (bleeding or VTE). Inverse-probability-of-treatment weighting (IPTW) was used to adjust for confounding.</p><p><strong>Results: </strong>We identified 1,130 eligible patients, of whom 124 patients (11%) received the reduced dose, and 1,006 patients (89%) received the standard dose. Bleeding occurred in one patient (0.8%) of the reduced dose group compared to 15 patients (1.5%) in the standard dose group (p > 0.99), VTE occurred in two patients (1.6%) in the reduced dose group compared to four patients (0.4%) in the standard dose group (p = 0.13). In the IPTW analysis, there was no significant difference in overall bleeding (odds ratio (OR) 1.4, 95% CI 0.18-10.75, p = 0.74), VTE (OR 0.3, 95% CI 0.05-1.81, p = 0.19), or the composite unfavourable outcome (OR 0.74, 95% CI 0.2-2.75, p = 0.66).</p><p><strong>Conclusion: </strong>There is no significant difference in the incidence of bleeding or VTE between the reduced dose and the standard dose of enoxaparin for VTE prophylaxis in underweight adult patients. Due to the low event rates in both groups, larger studies are required to delineate any differences between the two dosing strategies.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"45"},"PeriodicalIF":2.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}