Pub Date : 2025-09-25DOI: 10.1016/j.thromres.2025.109500
Zhongwang Wang , Zhengyu Yu , Ting Niu
Background
Venous thromboembolism (VTE) is the leading cause of 30-day postoperative mortality, with current guidelines recommending extended-duration thromboprophylaxis despite limited evidence on its impact on clinically meaningful benefits.
Objective
To evaluate the efficacy and safety of prolonged anticoagulant prophylaxis versus in-hospital only prophylaxis in cancer surgery patients using a meta-analysis of randomized controlled trials (RCTs).
Methods
We conducted a systematic review and meta-analysis of 10 RCTs. The primary outcomes included overall VTE, symptomatic VTE, pulmonary embolism (PE), major bleeding, and all-cause mortality. Results were summarized using relative ratios (RR) and 95 % confidence intervals (CIs).
Results
Prolonged prophylaxis significantly reduced the 30-day incidence of overall VTE (4.0 % vs. 10.0 %; RR 0.40, 95 %CI 0.22–0.76). No significant differences were observed in the 30-day incidence of symptomatic VTE (0.7 % vs. 1.1 %; RR 0.66, 95 %CI 0.29–1.48), PE (0.5 % vs. 0.5 %), or 90-day mortality (1.4 % vs. 1.6 %). A non-significant increase in major bleeding occurred (0.9 % vs. 0.2 %; RR 2.37, 95 %CI 0.79–7.11). Subgroup analyses indicated heterogeneity in primary outcomes based on surgical site (abdominopelvic vs. thoracic surgery).
Conclusion
While prolonged duration of pharmacological thromboprophylaxis reduces the incidence of overall VTE, it does not demonstrate clinically meaningful benefits for symptomatic events or survival. Current risk-stratification tools may overestimate thrombotic risk in cancer surgery patients receiving standard in-hospital prophylaxis. Our findings support a selective, rather than universal, approach to prolonged prophylaxis, emphasizing individualized risk assessment.
背景静脉血栓栓塞（VTE）是术后30天死亡率的主要原因，尽管目前的指南建议延长血栓预防时间，但其对临床有意义的益处的影响证据有限。目的通过随机对照试验（RCTs）的荟萃分析，评价癌症手术患者长期抗凝预防与仅住院预防的疗效和安全性。方法对10项随机对照试验进行系统评价和荟萃分析。主要结局包括总静脉血栓栓塞、症状性静脉血栓栓塞、肺栓塞（PE）、大出血和全因死亡率。采用相对比（RR）和95%置信区间（ci）对结果进行总结。结果延长预防可显著降低30天内静脉血栓栓塞发生率（4.0% vs 10.0%; RR 0.40, 95% CI 0.22-0.76）。在30天症状性静脉血栓栓塞发生率（0.7%对1.1%;RR 0.66, 95% CI 0.29-1.48）、PE（0.5%对0.5%）或90天死亡率（1.4%对1.6%）方面均无显著差异。大出血发生率无显著增加（0.9% vs. 0.2%; RR 2.37, 95% CI 0.79-7.11）。亚组分析显示，基于手术部位的主要结局存在异质性（腹盆腔与胸外科）。结论：虽然延长药物血栓预防治疗的时间可以降低静脉血栓栓塞的总发生率，但对于症状事件或生存并没有临床意义的益处。目前的风险分层工具可能高估了接受标准住院预防的癌症手术患者的血栓形成风险。我们的研究结果支持选择性的，而不是普遍的，长期预防的方法，强调个体化的风险评估。
{"title":"Prolonged duration of pharmacological thromboprophylaxis following oncologic surgery: A systematic review and meta-analysis of RCTs","authors":"Zhongwang Wang , Zhengyu Yu , Ting Niu","doi":"10.1016/j.thromres.2025.109500","DOIUrl":"10.1016/j.thromres.2025.109500","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE) is the leading cause of 30-day postoperative mortality, with current guidelines recommending extended-duration thromboprophylaxis despite limited evidence on its impact on clinically meaningful benefits.</div></div><div><h3>Objective</h3><div>To evaluate the efficacy and safety of prolonged anticoagulant prophylaxis versus in-hospital only prophylaxis in cancer surgery patients using a meta-analysis of randomized controlled trials (RCTs).</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis of 10 RCTs. The primary outcomes included overall VTE, symptomatic VTE, pulmonary embolism (PE), major bleeding, and all-cause mortality. Results were summarized using relative ratios (RR) and 95 % confidence intervals (CIs).</div></div><div><h3>Results</h3><div>Prolonged prophylaxis significantly reduced the 30-day incidence of overall VTE (4.0 % vs. 10.0 %; RR 0.40, 95 %CI 0.22–0.76). No significant differences were observed in the 30-day incidence of symptomatic VTE (0.7 % vs. 1.1 %; RR 0.66, 95 %CI 0.29–1.48), PE (0.5 % vs. 0.5 %), or 90-day mortality (1.4 % vs. 1.6 %). A non-significant increase in major bleeding occurred (0.9 % vs. 0.2 %; RR 2.37, 95 %CI 0.79–7.11). Subgroup analyses indicated heterogeneity in primary outcomes based on surgical site (abdominopelvic vs. thoracic surgery).</div></div><div><h3>Conclusion</h3><div>While prolonged duration of pharmacological thromboprophylaxis reduces the incidence of overall VTE, it does not demonstrate clinically meaningful benefits for symptomatic events or survival. Current risk-stratification tools may overestimate thrombotic risk in cancer surgery patients receiving standard in-hospital prophylaxis. Our findings support a selective, rather than universal, approach to prolonged prophylaxis, emphasizing individualized risk assessment.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"255 ","pages":"Article 109500"},"PeriodicalIF":3.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-22DOI: 10.1016/j.thromres.2025.109498
Ya Yang , Ning Wang , Lirong Xiong , Peishu Fu , Yanping Tian , Shenglin Luo , Fengjun Sun , Peiyuan Xia
Background
Thrombocytopenia is a common adverse side effects of Linezolid (LZD) but the underlying mechanism remains unclear. This study aimed to analyze the mechanism of LZD induced thrombocytopenia for LZD induced thrombocytopenia.
Methods
Cells proliferation, proplatelet formation assay and platelet production were evaluated in human megakaryoblastic leukemia cell line MEG-01 or C57BL/6 mice following LZD administration. The metabolic profiles and gene expression of MEG-01 cells was subsequently analyzed using molecular and bioinformatics techniques.
Results
LZD induced a dose- and time-dependent decrease in cells proliferation and inhibited proplatelet formation. It alters metabolic pathways including central carbon metabolism as indicated by a decrease in pyruvate, ATP and GTP levels (P < 0.01). Expression of genes related to energy production and conversion and the cytoskeleton were altered, such as SLC25A21, HBB, PRR5, MYL4 and RHoE (P < 0.01). Pyruvate supplementation rescued reduced metabolites induced by LZD, increased proplatelet formation of MEG-01 cells and length of pseudopod (P < 0.05). Furthermore, pyruvate rescued the counts of megakaryocytes in bone marrow and peripheral platelets in LZD treated mice (P < 0.05).
Conclusion
LZD inhibits mitochondrial energy metabolism, resulting in proplatelet formation reduction. Pyruvate reverses LZD induced thrombocytopenia, which provide a basis for mechanistic insights of LZD induced thrombocytopenia.
{"title":"Linezolid impair proplatelet formation by reducing mitochondrial energy metabolism in MEG-01 cells","authors":"Ya Yang , Ning Wang , Lirong Xiong , Peishu Fu , Yanping Tian , Shenglin Luo , Fengjun Sun , Peiyuan Xia","doi":"10.1016/j.thromres.2025.109498","DOIUrl":"10.1016/j.thromres.2025.109498","url":null,"abstract":"<div><h3>Background</h3><div>Thrombocytopenia is a common adverse side effects of Linezolid (LZD) but the underlying mechanism remains unclear. This study aimed to analyze the mechanism of LZD induced thrombocytopenia for LZD induced thrombocytopenia.</div></div><div><h3>Methods</h3><div>Cells proliferation, proplatelet formation assay and platelet production were evaluated in human megakaryoblastic leukemia cell line MEG-01 or C57BL/6 mice following LZD administration. The metabolic profiles and gene expression of MEG-01 cells was subsequently analyzed using molecular and bioinformatics techniques.</div></div><div><h3>Results</h3><div>LZD induced a dose- and time-dependent decrease in cells proliferation and inhibited proplatelet formation. It alters metabolic pathways including central carbon metabolism as indicated by a decrease in pyruvate, ATP and GTP levels (<em>P</em> < 0.01). Expression of genes related to energy production and conversion and the cytoskeleton were altered, such as <em>SLC25A21</em>, <em>HBB</em>, <em>PRR5</em>, <em>MYL4</em> and <em>RHoE</em> (<em>P</em> < 0.01). Pyruvate supplementation rescued reduced metabolites induced by LZD, increased proplatelet formation of MEG-01 cells and length of pseudopod (<em>P</em> < 0.05). Furthermore, pyruvate rescued the counts of megakaryocytes in bone marrow and peripheral platelets in LZD treated mice (<em>P</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>LZD inhibits mitochondrial energy metabolism, resulting in proplatelet formation reduction. Pyruvate reverses LZD induced thrombocytopenia, which provide a basis for mechanistic insights of LZD induced thrombocytopenia.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"255 ","pages":"Article 109498"},"PeriodicalIF":3.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patients with clinically significant bleeding, but with normal hemostatic investigations are identified as a distinct group known as “bleeding disorders of unknown cause” (BDUC). Though the clinical symptoms often resemble that of mild bleeding disorders (MBDs) with confirmed laboratory diagnosis, these patients have to go through multiple laboratory investigations only to end up in a diagnosis of exclusion i.e. BDUC. There are no standard protocols or general consensus on treatment of these patients, either for a generalized bleeding or prophylaxis prior to surgical procedures; patients are treated as per the physician perceptions or practices and many patients go untreated. Patients with BDUC are at increased risk of uncontrolled bleeding during trauma, surgery, and during delivery. Present review discusses the standard tests required for diagnosis of BDUC, type of bleeding, treatment modalities and future perspectives. Research should focus both on hemostatic, non-hemostatic and acquired factors contributing to bleeding. Evidence based diagnostic and treatment guidelines for this clinically mild group of patients are warranted for specific hemostatic interventions.
{"title":"Bleeding disorders of unknown cause: A conglomeration of disorders with heterogeneous etiology","authors":"Shrimati Shetty , Fiza Jivani , Aniket Kamble , Shruti Kharat , Kranti Patil , Gurpreet Kaur Saini , Anam Dhawlarker , Shrinath Kshirsagar , Savita Rangarajan","doi":"10.1016/j.thromres.2025.109496","DOIUrl":"10.1016/j.thromres.2025.109496","url":null,"abstract":"<div><div>Patients with clinically significant bleeding, but with normal hemostatic investigations are identified as a distinct group known as “bleeding disorders of unknown cause” (BDUC). Though the clinical symptoms often resemble that of mild bleeding disorders (MBDs) with confirmed laboratory diagnosis, these patients have to go through multiple laboratory investigations only to end up in a diagnosis of exclusion i.e. BDUC. There are no standard protocols or general consensus on treatment of these patients, either for a generalized bleeding or prophylaxis prior to surgical procedures; patients are treated as per the physician perceptions or practices and many patients go untreated. Patients with BDUC are at increased risk of uncontrolled bleeding during trauma, surgery, and during delivery. Present review discusses the standard tests required for diagnosis of BDUC, type of bleeding, treatment modalities and future perspectives. Research should focus both on hemostatic, non-hemostatic and acquired factors contributing to bleeding. Evidence based diagnostic and treatment guidelines for this clinically mild group of patients are warranted for specific hemostatic interventions.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"255 ","pages":"Article 109496"},"PeriodicalIF":3.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-22DOI: 10.1016/j.thromres.2025.109493
Ming Y. Lim , Jacob C. Cogan , Caroline Cromwell , Manila Gaddh , Radhika Gangaraju , Colleen Morton , Andrew Peseski , Rishabh Singh , Ishan Tatake , Kimberley Youkhana , Lisa Baumann Kreuziger
Introduction
Cardiovascular disease (CVD) is the leading cause of mortality worldwide, prompting increasing use of antiplatelet agents for primary and secondary prevention. Despite guidelines from multiple professional societies on the perioperative management of antiplatelet agents, we hypothesized that their implementation varies, leading to inconsistencies in perioperative practices across the United States (US).
Methods
We surveyed eleven members of the Systems-Based Hematology Committee of the Venous ThromboEmbolism Network US (VENUS) to gather their institutions' guidelines on the perioperative management of antiplatelet agents for non-cardiac surgery. Institutional guidelines were compared with five professional society guidelines.
Results
Of the 11 academic medical centers (AMCs), 8 (72.7 %) had institutional guidelines on perioperative management of antiplatelet agents (aspirin and three P2Y12 inhibitors) prior to non-cardiac surgery. Of the remaining three, two had guidelines on the management of antiplatelet agents prior to interventional radiology procedures (n = 1) and for neuraxial anesthesia (n = 1).
Five AMCs gave differing recommendations on managing phosphodiesterase inhibitors perioperatively, while none of the five society guidelines addressed them.
Five AMCs provided variable recommendations on the timing of postoperative resumption of antiplatelet agents ranging from as soon as possible to 12–24 h postoperatively depending on bleeding risk.
Only two AMCs provided recommendations for those on antiplatelet agents who have life-threatening peri-operative bleeding or undergoing urgent high-bleeding risk surgery.
Conclusion
AMCs vary in their recommendations on the perioperative management of antiplatelet agents prior to non-cardiac surgery. Further research is needed to determine if this variability impacts patient outcomes and to identify ways to improve guideline implementation.
{"title":"Comparative analysis of perioperative management of antiplatelet agent guidelines across US institutions","authors":"Ming Y. Lim , Jacob C. Cogan , Caroline Cromwell , Manila Gaddh , Radhika Gangaraju , Colleen Morton , Andrew Peseski , Rishabh Singh , Ishan Tatake , Kimberley Youkhana , Lisa Baumann Kreuziger","doi":"10.1016/j.thromres.2025.109493","DOIUrl":"10.1016/j.thromres.2025.109493","url":null,"abstract":"<div><h3>Introduction</h3><div>Cardiovascular disease (CVD) is the leading cause of mortality worldwide, prompting increasing use of antiplatelet agents for primary and secondary prevention. Despite guidelines from multiple professional societies on the perioperative management of antiplatelet agents, we hypothesized that their implementation varies, leading to inconsistencies in perioperative practices across the United States (US).</div></div><div><h3>Methods</h3><div>We surveyed eleven members of the Systems-Based Hematology Committee of the Venous ThromboEmbolism Network US (VENUS) to gather their institutions' guidelines on the perioperative management of antiplatelet agents for non-cardiac surgery. Institutional guidelines were compared with five professional society guidelines.</div></div><div><h3>Results</h3><div>Of the 11 academic medical centers (AMCs), 8 (72.7 %) had institutional guidelines on perioperative management of antiplatelet agents (aspirin and three P2Y<sub>12</sub> inhibitors) prior to non-cardiac surgery. Of the remaining three, two had guidelines on the management of antiplatelet agents prior to interventional radiology procedures (<em>n</em> = 1) and for neuraxial anesthesia (<em>n</em> = 1).</div><div>Five AMCs gave differing recommendations on managing phosphodiesterase inhibitors perioperatively, while none of the five society guidelines addressed them.</div><div>Five AMCs provided variable recommendations on the timing of postoperative resumption of antiplatelet agents ranging from as soon as possible to 12–24 h postoperatively depending on bleeding risk.</div><div>Only two AMCs provided recommendations for those on antiplatelet agents who have life-threatening peri-operative bleeding or undergoing urgent high-bleeding risk surgery.</div></div><div><h3>Conclusion</h3><div>AMCs vary in their recommendations on the perioperative management of antiplatelet agents prior to non-cardiac surgery. Further research is needed to determine if this variability impacts patient outcomes and to identify ways to improve guideline implementation.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"255 ","pages":"Article 109493"},"PeriodicalIF":3.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patients with chronic kidney disease (CKD), especially those with end stage renal disease (ESRD) are prone to both bleeding and thrombosis. We aimed to evaluate several hemostasis parameters and identify any differences in the coagulation process among patients with CKD at different stages.
Methods
This cross-sectional study included patients with CKD stages 2 to5 (non-dialysis) and ESRD patients on hemodialysis (HD) or peritoneal dialysis (PD). Standard coagulation tests were performed, along with thromboelastography (TEG) and platelet function analyze (PFA).
Results
A total of 148 patients were included in the analysis, mean age 65.6 ± 14.3 years; 75 % males; 76 % hypertensive. Significant differences were identified across all groups, particularly between CKD stages 2 and 5, in D-Dimers, FVIII, homocysteine, fibrinogen, von Willebrand factor (vWF), aPTT and TEG parameters (maximal amplitude [MA], K time, A angle), with values progressively increasing as CKD advanced (all p < 0.05). The PD and HD groups had major differences in FVIII, vWF, PFA and TEG parameters, with PD patients being more hypercoagulable. PFA values did not correlate with TEG parameters, while platelet count correlated with both PFA and MA values. eGFR independently predicted most of the coagulation and TEG parameters tested.
Conclusion
CKD progression affects TEG, PFA, and most coagulation examinations, indicating a prothrombotic profile even in the early stages of CKD. Moreover, significant differences in coagulation parameters are observed between HD and PD patients, with the latter exhibiting a more pronounced hypercoagulable state. These results should be interpreted cautiously, considering the limitations and the possible confounders of the study.
{"title":"Comparative evaluation of coagulation profiles across different stages of chronic kidney disease: A cross-sectional study","authors":"Emelina Stambolliu , Panagiota Giannou , Aikaterini Damianaki , Maria Panagiota Terzi , Euthymia Pavlou , Elpiniki Stathopoulou , Efrossyni Nomikou , Dimitrios Petras","doi":"10.1016/j.thromres.2025.109497","DOIUrl":"10.1016/j.thromres.2025.109497","url":null,"abstract":"<div><h3>Background and aims</h3><div>Patients with chronic kidney disease (CKD), especially those with end stage renal disease (ESRD) are prone to both bleeding and thrombosis. We aimed to evaluate several hemostasis parameters and identify any differences in the coagulation process among patients with CKD at different stages.</div></div><div><h3>Methods</h3><div>This cross-sectional study included patients with CKD stages 2 to5 (non-dialysis) and ESRD patients on hemodialysis (HD) or peritoneal dialysis (PD). Standard coagulation tests were performed, along with thromboelastography (TEG) and platelet function analyze (PFA).</div></div><div><h3>Results</h3><div>A total of 148 patients were included in the analysis, mean age 65.6 ± 14.3 years; 75 % males; 76 % hypertensive. Significant differences were identified across all groups, particularly between CKD stages 2 and 5, in D-Dimers, FVIII, homocysteine, fibrinogen, von Willebrand factor (vWF), aPTT and TEG parameters (maximal amplitude [MA], K time, A angle), with values progressively increasing as CKD advanced (all <em>p</em> < 0.05). The PD and HD groups had major differences in FVIII, vWF, PFA and TEG parameters, with PD patients being more hypercoagulable. PFA values did not correlate with TEG parameters, while platelet count correlated with both PFA and MA values. eGFR independently predicted most of the coagulation and TEG parameters tested.</div></div><div><h3>Conclusion</h3><div>CKD progression affects TEG, PFA, and most coagulation examinations, indicating a prothrombotic profile even in the early stages of CKD. Moreover, significant differences in coagulation parameters are observed between HD and PD patients, with the latter exhibiting a more pronounced hypercoagulable state. These results should be interpreted cautiously, considering the limitations and the possible confounders of the study.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"255 ","pages":"Article 109497"},"PeriodicalIF":3.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-21DOI: 10.1016/j.thromres.2025.109499
Karsten Keller , Volker H. Schmitt , Visvakanth Sivanathan , Omar Hahad , Thomas Münzel , Philipp Lurz , Christine Espinola-Klein , Stefano Barco , Stavros Konstantinides , Lukas Hobohm
Background
Pulmonary embolism (PE) and cystic fibrosis (CF) are both diseases that impact the cardiovascular-pulmonary system. While CF is a rare heterogeneous monogenetic autosomal-recessive inherited multisystem-disease that reduces life-expectancy, PE is a common emergency event with also high morbidity and mortality. We aimed to investigate the impact of CF on prognosis of PE patients.
Methods
The German nationwide inpatient sample was used for this study. All patient-cases of patients with PE in Germany 2005–2020 were included and stratified for CF.
Results
Overall, 1,373,084 patient-cases of PE patients (median age 72.0 years, 53.0 % females) in Germany were included in our study 2005–2020. Among these, 126 patients (0.01 %) were coded with CF.
PE patients with CF were younger (33.0 [24.0–43.0] vs. 72.0 [60.0–80.0] years, P < 0.001) displaying a lower prevalence of arterial hypertension, hyperlipidemia and lower comorbidity-burden (Charlson comorbidity index: 2.0 [1.0–4.0] vs. 4.0 [3.0–7.0], P < 0.001) compared to those without CF. In contrast, diabetes mellitus was more frequent in PE patients with CF (49.2 % vs. 18.7 %, P < 0.001).
After adjustment for age, sex and comorbidities, CF was associated with higher case-fatality (OR 2.451 [95 % CI 1.542–3.896], P < 0.001), pneumonia (OR 1.518 [95 % CI 1.059–2.176], P = 0.023) and necessity regarding transfusion of blood constituents (OR 3.702 [95 % CI 2.540–5.396], P < 0.001).
Conclusions
PE patients with CF were younger at the time of PE event and accompanied by typical comorbidities such as diabetes mellitus and renal disease compared to PE patients without CF. CF was associated with higher complication rates comprising pneumonia, bleeding events and 2.5-fold increased case-fatality.
肺栓塞（PE）和囊性纤维化（CF）都是影响心血管-肺系统的疾病。CF是一种罕见的异源单基因常染色体隐性遗传性多系统疾病，可降低预期寿命，而PE是一种常见的紧急事件，发病率和死亡率也很高。我们旨在探讨CF对PE患者预后的影响。方法采用德国全国住院患者样本进行研究。我们纳入了2005-2020年德国所有PE患者，并对其进行了cf分层。结果2005-2020年，我们共纳入了1373084例PE患者（中位年龄72.0岁，53.0%为女性）。其中126例（0.01%）被编码为CF。CF的PE患者较年轻（33.0[24.0-43.0]比72.0[60.0-80.0]岁，P < 0.001），动脉高血压、高脂血症的患病率较低，合并症负担较低（Charlson合并症指数：2.0[1.0-4.0]比4.0 [3.0-7.0],P < 0.001）。相比之下，CF的PE患者糖尿病发生率更高（49.2%比18.7%,P < 0.001）。在调整了年龄、性别和合并症后，CF与较高的病死率（OR 2.451 [95% CI 1.542-3.896], P < 0.001）、肺炎（OR 1.518 [95% CI 1.059-2.176], P = 0.023）和输血必要性（OR 3.702 [95% CI 2.540-5.396], P < 0.001）相关。结论spe合并CF患者在PE事件发生时较未合并CF的PE患者更年轻，并伴有糖尿病、肾脏疾病等典型合并症。CF的并发症发生率更高，包括肺炎、出血事件，病死率增加2.5倍。
{"title":"Cystic fibrosis and its impact on prognosis in pulmonary embolism","authors":"Karsten Keller , Volker H. Schmitt , Visvakanth Sivanathan , Omar Hahad , Thomas Münzel , Philipp Lurz , Christine Espinola-Klein , Stefano Barco , Stavros Konstantinides , Lukas Hobohm","doi":"10.1016/j.thromres.2025.109499","DOIUrl":"10.1016/j.thromres.2025.109499","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary embolism (PE) and cystic fibrosis (CF) are both diseases that impact the cardiovascular-pulmonary system. While CF is a rare heterogeneous monogenetic autosomal-recessive inherited multisystem-disease that reduces life-expectancy, PE is a common emergency event with also high morbidity and mortality. We aimed to investigate the impact of CF on prognosis of PE patients.</div></div><div><h3>Methods</h3><div>The German nationwide inpatient sample was used for this study. All patient-cases of patients with PE in Germany 2005–2020 were included and stratified for CF.</div></div><div><h3>Results</h3><div>Overall, 1,373,084 patient-cases of PE patients (median age 72.0 years, 53.0 % females) in Germany were included in our study 2005–2020. Among these, 126 patients (0.01 %) were coded with CF.</div><div>PE patients with CF were younger (33.0 [24.0–43.0] vs. 72.0 [60.0–80.0] years, <em>P</em> < 0.001) displaying a lower prevalence of arterial hypertension, hyperlipidemia and lower comorbidity-burden (Charlson comorbidity index: 2.0 [1.0–4.0] vs. 4.0 [3.0–7.0], <em>P</em> < 0.001) compared to those without CF. In contrast, diabetes mellitus was more frequent in PE patients with CF (49.2 % vs. 18.7 %, <em>P</em> < 0.001).</div><div>After adjustment for age, sex and comorbidities, CF was associated with higher case-fatality (OR 2.451 [95 % CI 1.542–3.896], <em>P</em> < 0.001), pneumonia (OR 1.518 [95 % CI 1.059–2.176], <em>P</em> = 0.023) and necessity regarding transfusion of blood constituents (OR 3.702 [95 % CI 2.540–5.396], P < 0.001).</div></div><div><h3>Conclusions</h3><div>PE patients with CF were younger at the time of PE event and accompanied by typical comorbidities such as diabetes mellitus and renal disease compared to PE patients without CF. CF was associated with higher complication rates comprising pneumonia, bleeding events and 2.5-fold increased case-fatality.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"255 ","pages":"Article 109499"},"PeriodicalIF":3.4,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-20DOI: 10.1016/j.thromres.2025.109484
Luis Ortega-Paz , Azita H. Talasaz , Parham Sadeghipour , Sina Rashedi , Jean M. Connors , Dominick J. Angiolillo , Larisa H. Cavallari , David Jimenez , Gabriela Bastidas , Elizabeth Lorenzi , Lindsay R. Berry , Thomas Hills , Daniel Francis McAuley , Tayyab Shah , Alexandra J. Lansky , Siddharthan Deepti , Hernando Guillermo Gaitán-Duarte , Tatjana S. Potpara , Mattia Galli , Dave L. Dixon , Behnood Bikdeli
Aims
Statins may impact COVID-19 outcomes through lipid-mediated and lipid-independent pathways. However, the clinical impact of statin therapy among hospitalized patients with COVID-19 remains unclear due to the limited power of existing randomized controlled trials (RCTs).
Methods
A systematic search of PubMed, Embase, and clinicaltrials.gov was conducted through July 17th, 2024. RCTs were included if they compared statin therapy to control (placebo or standard care) in hospitalized COVID-19 patients and enrolled at least 250 randomized participants. Studies with co-treatment were considered in sensitivity analyses. The primary effectiveness outcome was 30-day all-cause death. The main safety outcomes were myopathy and rise in liver enzymes.
Results
Three RCTs were included in the main analysis (3882 statin-naive patients, 33.7 % female, average follow-up duration 37 days). Compared with control, statin therapy was associated with reduced all-cause death (20.9 % vs. 23.8 %; odds ratio [OR]: 0.82, 95 % confidence interval [CI] 0.70–0.96; P = 0.01), with a small but significant increase in myopathy (0.6 % vs. 0 %; risk difference: 0.00, 95 % CI -0.00; 0.01), and no significant difference in liver enzyme abnormalities (1.0 % vs. 1.4 %; OR 1.00, 95 % CI: 0.25–3.99). A sensitivity analysis including two additional RCTs that included randomized co-treatments yielded similar findings. There were no significant interactions for effectiveness by disease severity (critically vs. non-critically ill, P = 0.38) or sex (males vs. females, P = 0.83).
Conclusion
Among hospitalized patients with COVID-19, statin therapy was associated with a significant reduction in 30-day all-cause death compared with control and exhibited an excellent safety profile.
Study registration
This study is registered in PROSPERO (CRD42023478764).
目的他汀类药物可能通过脂质介导和脂质非依赖性途径影响COVID-19的结局。然而，由于现有随机对照试验（rct）的有效性有限，他汀类药物治疗对COVID-19住院患者的临床影响尚不清楚。方法系统检索PubMed、Embase和clinicaltrials.gov，检索时间截止到2024年7月17日。如果将住院的COVID-19患者的他汀类药物治疗与对照组（安慰剂或标准治疗）进行比较，并纳入至少250名随机受试者，则纳入随机对照试验。在敏感性分析中考虑了联合治疗的研究。主要有效终点为30天全因死亡。主要的安全性结果是肌病和肝酶升高。结果3项随机对照试验（rct）纳入主分析（3882例他汀类药物初治患者，女性33.7%，平均随访时间37 d）。与对照组相比，他汀类药物治疗与全因死亡率降低相关（20.9% vs. 23.8%；优势比[OR]: 0.82, 95%可信区间[CI] 0.70-0.96; P = 0.01），肌病发生率虽小但显著升高（0.6% vs. 0%；风险差：0.00,95% CI -0.00; 0.01），肝酶异常发生率无显著差异（1.0% vs. 1.4%; OR 1.00, 95% CI: 0.25-3.99）。包括另外两项随机联合治疗的随机对照试验的敏感性分析得出了类似的结果。疾病严重程度（危重症vs.非危重症，P = 0.38）或性别（男性vs.女性，P = 0.83）对疗效没有显著的相互作用。结论在COVID-19住院患者中，与对照组相比，他汀类药物治疗与30天全因死亡率显著降低相关，并表现出良好的安全性。研究注册本研究已在PROSPERO注册（CRD42023478764）。
{"title":"Safety and effectiveness of statins in hospitalized patients with COVID-19: Systematic review and collaborative meta-analysis of randomized controlled trials","authors":"Luis Ortega-Paz , Azita H. Talasaz , Parham Sadeghipour , Sina Rashedi , Jean M. Connors , Dominick J. Angiolillo , Larisa H. Cavallari , David Jimenez , Gabriela Bastidas , Elizabeth Lorenzi , Lindsay R. Berry , Thomas Hills , Daniel Francis McAuley , Tayyab Shah , Alexandra J. Lansky , Siddharthan Deepti , Hernando Guillermo Gaitán-Duarte , Tatjana S. Potpara , Mattia Galli , Dave L. Dixon , Behnood Bikdeli","doi":"10.1016/j.thromres.2025.109484","DOIUrl":"10.1016/j.thromres.2025.109484","url":null,"abstract":"<div><h3>Aims</h3><div>Statins may impact COVID-19 outcomes through lipid-mediated and lipid-independent pathways. However, the clinical impact of statin therapy among hospitalized patients with COVID-19 remains unclear due to the limited power of existing randomized controlled trials (RCTs).</div></div><div><h3>Methods</h3><div>A systematic search of PubMed, Embase, and <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> was conducted through July 17th, 2024. RCTs were included if they compared statin therapy to control (placebo or standard care) in hospitalized COVID-19 patients and enrolled at least 250 randomized participants. Studies with co-treatment were considered in sensitivity analyses. The primary effectiveness outcome was 30-day all-cause death. The main safety outcomes were myopathy and rise in liver enzymes.</div></div><div><h3>Results</h3><div>Three RCTs were included in the main analysis (3882 statin-naive patients, 33.7 % female, average follow-up duration 37 days). Compared with control, statin therapy was associated with reduced all-cause death (20.9 % vs. 23.8 %; odds ratio [OR]: 0.82, 95 % confidence interval [CI] 0.70–0.96; <em>P</em> = 0.01), with a small but significant increase in myopathy (0.6 % vs. 0 %; risk difference: 0.00, 95 % CI -0.00; 0.01), and no significant difference in liver enzyme abnormalities (1.0 % vs. 1.4 %; OR 1.00, 95 % CI: 0.25–3.99). A sensitivity analysis including two additional RCTs that included randomized co-treatments yielded similar findings. There were no significant interactions for effectiveness by disease severity (critically vs. non-critically ill, <em>P</em> = 0.38) or sex (males vs. females, <em>P</em> = 0.83).</div></div><div><h3>Conclusion</h3><div>Among hospitalized patients with COVID-19, statin therapy was associated with a significant reduction in 30-day all-cause death compared with control and exhibited an excellent safety profile.</div></div><div><h3>Study registration</h3><div>This study is registered in PROSPERO (CRD42023478764).</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"255 ","pages":"Article 109484"},"PeriodicalIF":3.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-20DOI: 10.1016/j.thromres.2025.109492
Antonia Perez Martin , Lucas Léger , Mathias Chéa , Thierry Boudemaghe , Jean-Christophe Gris
Introduction
Seasonality of Pulmonary Embolism (PE) is increasingly described, suggesting the negative impact of cold meteorological conditions. Yet, little is known about geographical and climatic impact. With various climates, and large regional temperature ranges, France provides a model for highlighting climate-related differences in PE prevalence. We thus made a whole country, 8-year retrospective analysis of PE prevalence, per season and geographical area, using standardized sex and age strata.
Methods
The French Hospital Discharge Database provided data on in-hospital-managed PE, with sex, age and geographical codes to calculate the standardized prevalence of PE (PE-SP) and map its geographical distribution. Climatic conditions were estimated taking average regional temperatures. Results: From 2012 to 2019, we identified 341,365 cases of PE (median age, 71y; 53.04 % female). PE-SP shows constant seasonality, with a higher incidence during the coldest months (globally +28.4 %), a peak in February and a trough in June (0.272 and 0.218 cases per 100,000 inhabitants respectively).
PE-SP also exhibits a marked territorial gradient, increasing from West to East and South to North, with a median magnitude of 86.9 %, (IQR 73.3 %–98.4 %, extreme values 50.1 %–133 %). This gradient remains whatever the sex or age, and over seasons and years. Finally, linear regression analysis, expressing PE-SP according to climatic conditions, found a significant association with TXQ10 (10th percentile of daily temperatures), highlighting higher PE-SP in geographical areas traditionally exposed to colder weather.
Conclusions
In France, PE occurrence is heterogeneously distributed, over seasons and also over territories. Geographical (seasonal and territorial) patient biotope should be considered regarding the thrombotic risk.
{"title":"Seasonality and territorial gradient of pulmonary embolism in France: an 8-year retrospective nationwide analysis","authors":"Antonia Perez Martin , Lucas Léger , Mathias Chéa , Thierry Boudemaghe , Jean-Christophe Gris","doi":"10.1016/j.thromres.2025.109492","DOIUrl":"10.1016/j.thromres.2025.109492","url":null,"abstract":"<div><h3>Introduction</h3><div>Seasonality of Pulmonary Embolism (PE) is increasingly described, suggesting the negative impact of cold meteorological conditions. Yet, little is known about geographical and climatic impact. With various climates, and large regional temperature ranges, France provides a model for highlighting climate-related differences in PE prevalence. We thus made a whole country, 8-year retrospective analysis of PE prevalence, per season and geographical area, using standardized sex and age strata.</div></div><div><h3>Methods</h3><div>The French Hospital Discharge Database provided data on in-hospital-managed PE, with sex, age and geographical codes to calculate the standardized prevalence of PE (PE-SP) and map its geographical distribution. Climatic conditions were estimated taking average regional temperatures. <strong><em>Results</em>:</strong> From 2012 to 2019, we identified 341,365 cases of PE (median age, 71y; 53.04 % female). PE-SP shows constant seasonality, with a higher incidence during the coldest months (globally +28.4 %), a peak in February and a trough in June (0.272 and 0.218 cases per 100,000 inhabitants respectively).</div><div>PE-SP also exhibits a marked territorial gradient, increasing from West to East and South to North, with a median magnitude of 86.9 %, (IQR 73.3 %–98.4 %, extreme values 50.1 %–133 %). This gradient remains whatever the sex or age, and over seasons and years. Finally, linear regression analysis, expressing PE-SP according to climatic conditions, found a significant association with TXQ10 (10th percentile of daily temperatures), highlighting higher PE-SP in geographical areas traditionally exposed to colder weather.</div></div><div><h3>Conclusions</h3><div>In France, PE occurrence is heterogeneously distributed, over seasons and also over territories. Geographical (seasonal and territorial) patient biotope should be considered regarding the thrombotic risk.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"255 ","pages":"Article 109492"},"PeriodicalIF":3.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sepsis-associated disseminated intravascular coagulation (DIC) contributes to multiple organ dysfunction and increases mortality. Although DIC resolution is considered a therapeutic goal, its validity as a surrogate outcome remains unclear. Identifying key prognostic markers within the DIC score may improve treatment strategies. This study aimed to evaluate the association between DIC resolution and 28-d mortality in patients with sepsis-associated DIC treated with antithrombin and to assess the prognostic value of DIC score components. This study analyzed 2291 patients with sepsis-associated DIC using data from a nationwide post-marketing surveillance of antithrombin concentrates in Japan. Survival analysis and multivariate models were used to assess the associations among DIC resolution, DIC score components, and 28-d mortality. Patients with resolved DIC by day 6 had a significantly lower 28-d mortality rate than those with persistent DIC. Early resolution by day 3 correlated with better survival. Platelet count and prothrombin time-international normalized ratio (PT-INR) were the strongest predictors of mortality, whereas fibrin/fibrinogen degradation product had limited prognostic value. Even among patients with persistent DIC, improvements in the PT-INR and platelet count were associated with better survival. High-dose antithrombin increased DIC resolution rates and showed a trend toward reduced mortality, although the reduction was not statistically significant. DIC resolution is associated with improved survival and may serve as a surrogate outcome. Monitoring key coagulation markers, even in unresolved cases, may help refine the treatment strategies for sepsis-associated DIC. These findings may support future clinical trials targeting coagulopathy in patients with sepsis.
{"title":"Disseminated intravascular coagulation resolution as a surrogate outcome for mortality in sepsis-associated disseminated intravascular coagulation","authors":"Takeshi Wada , Tomoki Tanigawa , Yuki Shiko , Kazuma Yamakawa , Satoshi Gando","doi":"10.1016/j.thromres.2025.109485","DOIUrl":"10.1016/j.thromres.2025.109485","url":null,"abstract":"<div><div>Sepsis-associated disseminated intravascular coagulation (DIC) contributes to multiple organ dysfunction and increases mortality. Although DIC resolution is considered a therapeutic goal, its validity as a surrogate outcome remains unclear. Identifying key prognostic markers within the DIC score may improve treatment strategies. This study aimed to evaluate the association between DIC resolution and 28-d mortality in patients with sepsis-associated DIC treated with antithrombin and to assess the prognostic value of DIC score components. This study analyzed 2291 patients with sepsis-associated DIC using data from a nationwide post-marketing surveillance of antithrombin concentrates in Japan. Survival analysis and multivariate models were used to assess the associations among DIC resolution, DIC score components, and 28-d mortality. Patients with resolved DIC by day 6 had a significantly lower 28-d mortality rate than those with persistent DIC. Early resolution by day 3 correlated with better survival. Platelet count and prothrombin time-international normalized ratio (PT-INR) were the strongest predictors of mortality, whereas fibrin/fibrinogen degradation product had limited prognostic value. Even among patients with persistent DIC, improvements in the PT-INR and platelet count were associated with better survival. High-dose antithrombin increased DIC resolution rates and showed a trend toward reduced mortality, although the reduction was not statistically significant. DIC resolution is associated with improved survival and may serve as a surrogate outcome. Monitoring key coagulation markers, even in unresolved cases, may help refine the treatment strategies for sepsis-associated DIC. These findings may support future clinical trials targeting coagulopathy in patients with sepsis.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"255 ","pages":"Article 109485"},"PeriodicalIF":3.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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