Robert J. Trager , Catherine P. Haering , Anthony N. Baumann , Debbie S. Wright
{"title":"Association between combined oral contraceptive prescription and cervical artery dissection: A retrospective cohort study","authors":"Robert J. Trager , Catherine P. Haering , Anthony N. Baumann , Debbie S. Wright","doi":"10.1016/j.thromres.2025.109279","DOIUrl":"10.1016/j.thromres.2025.109279","url":null,"abstract":"<div><h3>Background</h3><div>To date, research has identified positive associations between combined oral contraceptives (COCs) and adverse vascular events, however, evidence regarding the possible association with cervical artery dissection (CeAD) remains limited. We tested the hypothesis of a positive association between COCs and CeAD within one year following COC initiation compared to matched controls initiating intrauterine devices (IUDs), as measured by risk ratio (RR).</div></div><div><h3>Methods</h3><div>We queried de-identified United States health records data (TriNetX, Inc.) from 2014 to 2024 for females aged 15–50 years without previous cerebrovascular disease or CeAD, creating mutually exclusive cohorts initiating either COCs or IUDs. We used propensity matching to control for variables associated with CeAD. Our primary outcome included the RR for CeAD within one year follow-up. We secondarily explored cumulative CeAD incidence and RR of stroke, also examining outcomes for females with ≥2 COC prescriptions (COC2).</div></div><div><h3>Results</h3><div>After matching there were 214,020 patients per cohort (mean age 31 years). The incidence and risk of CeAD was greater among those prescribed COCs compared to matched controls with IUDs [95 % CI] (COCs: 0.016 %, IUDs: 0.008 %; RR 1.94 [1.10,3.43]; <em>P</em> = 0.0195). A similar association was observed for stroke (COCs: 0.106 %, IUDs: 0.057 %; RR = 1.86 [1.49,2.32]; <em>P</em> < 0.0001). The secondary COC2 analysis revealed similar findings.</div></div><div><h3>Conclusions</h3><div>The present findings suggest that females prescribed COCs have an increased risk of CeAD and stroke compared to matched controls using IUDs. These observations should be viewed as preliminary, require corroboration by other studies, and in isolation do not replace the broader clinical and shared decision-making regarding contraceptive use.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"247 ","pages":"Article 109279"},"PeriodicalIF":3.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aya Takemoto , Nobuyo Kondo , Akiko Kitajo , Hiroto Yamamoto , Yudai Yamamoto , Koji Higashino , Tokujiro Uchida
{"title":"Dielectric blood coagulometry to evaluate coagulation activity in patients prescribed factor Xa inhibitors undergoing elective surgery: A prospective observational study","authors":"Aya Takemoto , Nobuyo Kondo , Akiko Kitajo , Hiroto Yamamoto , Yudai Yamamoto , Koji Higashino , Tokujiro Uchida","doi":"10.1016/j.thromres.2025.109283","DOIUrl":"10.1016/j.thromres.2025.109283","url":null,"abstract":"<div><h3>Background</h3><div>Dielectric blood coagulometry (DBCM) is a coagulation test based on dielectric permittivity. We recently developed a new cartridge to evaluate the anticoagulation effect of factor Xa inhibitors and investigated the usefulness of this system in the clinical setting. Here, we evaluate the relationship among the coagulation time measured by DBCM, plasma concentrations of factor Xa inhibitors, and peak thrombin generation using blood samples from patients prescribed factor Xa inhibitors undergoing elective surgery.</div></div><div><h3>Methods</h3><div>Whole-blood samples were collected at the preoperative visit and after anesthetic induction in the operating room, and our cartridge was used to measure the coagulation time by DBCM. Plasma was used to evaluate thrombin generation and to perform in vitro quantification of factor Xa inhibitors. Spearman's correlation was used to analyze correlations, and receiver operating characteristic (ROC) curves were used to evaluate diagnostic performance.</div></div><div><h3>Results</h3><div>The DBCM coagulation time correlated with plasma factor Xa inhibitor concentrations (Rs = 0.87 for apixaban [<em>n</em> = 57, <em>P</em> < 0.001]; Rs = 0.91 for rivaroxaban [<em>n</em> = 49, <em>P</em> < 0.001]) and peak thrombin generation (Rs = −0.80 for apixaban [<em>n</em> = 57, <em>P</em> < 0.001]; Rs = −0.84 for rivaroxaban [<em>n</em> = 49, P < 0.001]). Samples with factor Xa inhibitor concentrations <30 ng/mL had an area under the ROC curve of 0.98 (95 % confidence interval 0.96–1.0) for apixaban and 0.99 (95 % confidence interval 0.99–1.0) for rivaroxaban.</div></div><div><h3>Conclusions</h3><div>DBCM was a useful point-of-care test to evaluate the anticoagulation effect induced by factor Xa inhibitors.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"247 ","pages":"Article 109283"},"PeriodicalIF":3.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372675","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}
C. Farkh , P.H. Wicky , A. Perrier-Cornet , M. Koskas , N. Ajzenberg , D. Faille
{"title":"Danaparoid failure in heparin-induced thrombocytopenia due to acquired antithrombin deficiency: A case report","authors":"C. Farkh , P.H. Wicky , A. Perrier-Cornet , M. Koskas , N. Ajzenberg , D. Faille","doi":"10.1016/j.thromres.2025.109280","DOIUrl":"10.1016/j.thromres.2025.109280","url":null,"abstract":"<div><div>Heparin-induced thrombocytopenia (HIT) is a severe immunological adverse effect of heparin therapy, characterized by thrombocytopenia and unpredictable thromboembolic complications. Rapid discontinuation of heparin and replacement by an alternative anticoagulant such as danaparoid is mandatory. We report the case of a 45-year-old woman with uterine sarcoma and acute HIT, who experienced treatment failure with danaparoid. Despite danaparoid dosage escalation, anti-Xa activity remained subtherapeutic, resulting in clinical deterioration. Acquired antithrombin (AT) deficiency in the context of cancer and HIT -associated disseminated intravascular coagulation was then diagnosed. The administration of AT concentrate corrected AT levels thereby restoring therapeutic anti-Xa levels. This is the first reported case of danaparoid failure due to a documented AT deficiency demonstrating the potential efficacy of AT supplementation in this context. This case highlights the importance of monitoring AT levels in HIT patients when danaparoid activity is below the therapeutic range despite adjusted dosing.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"247 ","pages":"Article 109280"},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372677","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}
{"title":"Complement system activation through the alternative pathway associates with disseminated intravascular coagulation to increase mortality in sepsis","authors":"Tomohiro Abe , Katsutoshi Saito , Takehiko Nagano , Yusuke Yamada , Hidenobu Ochiai","doi":"10.1016/j.thromres.2025.109281","DOIUrl":"10.1016/j.thromres.2025.109281","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced disseminated intravascular coagulation (DIC) increases mortality in sepsis patients. Complement system activation is concomitant with sepsis-induced DIC; however, it is unclear how these two pathologies influence clinical parameters of sepsis individually and in combination, and which of the complement pathways activation is predominantly associated with mortality.</div></div><div><h3>Methods</h3><div>In this ancillary analysis of a prospective observational study, 49 adult sepsis patients were assigned to four groups according to the absence/presence of DIC and complement activation. Effects of complement activation and DIC on clinical demographics including parameters of DIC, systemic severities, and 60-days all-cause mortality were assessed by comparing the groups. We analyzed each complement pathway by comparing Bb, C3a/C3 ratio, SC5b-9/C3 ratio, C4d, C4d/C4 ratio, C3a, C5a, and SC5b-9 between survivors/non-survivors both in all the patients and in the DIC+ subgroup.</div></div><div><h3>Results</h3><div>Complement system activation induced thrombocytopenia and enhanced sepsis severity measured as APACHE2 and SOFA scores. 60-days all-cause mortality was different between groups, with 0 % in the complement activation alone group, 14 % in the DIC alone group and 66 % in the combined DIC and complement activation group. Bb and C3a/C3 and SC5b-9/C3 ratios were higher in non-survivors, with Bb and SC5b-9/C3 ratio still higher in DIC+ non-survivors.</div></div><div><h3>Conclusion</h3><div>Complement activation worsen the severity of sepsis and cause thrombocytopenia. Co-occurrence of complement activation and DIC increased sepsis mortality. The alternative pathway of complement activation plays a major role in sepsis mortality.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"247 ","pages":"Article 109281"},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395669","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}
Suzanne Irani, Xiaokui Gu, Brian Haymart, Constantina Alexandris-Souphis, Helen Gikas, Mona Ali, Scott Kaatz, Joey Maniaci, Linda Perry, Mary Jo Deyoung, Stacy Ellsworth, James Froehlich, Eva Kline Rogers, Noelle Ryan, Geoffrey Barnes
{"title":"Analysis of quality measures before and after switching care models in MAQI2 anticoagulation clinics","authors":"Suzanne Irani, Xiaokui Gu, Brian Haymart, Constantina Alexandris-Souphis, Helen Gikas, Mona Ali, Scott Kaatz, Joey Maniaci, Linda Perry, Mary Jo Deyoung, Stacy Ellsworth, James Froehlich, Eva Kline Rogers, Noelle Ryan, Geoffrey Barnes","doi":"10.1016/j.thromres.2025.109278","DOIUrl":"10.1016/j.thromres.2025.109278","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"247 ","pages":"Article 109278"},"PeriodicalIF":3.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143301813","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}
Floris T.M. Bosch , Frederike Dijk , Saskia Briedé , Jesse V. Groen , Randa G. Hanna-Sawires , Hans Halfwerk , Frederikus A. Klok , Karin A.H. Kaasjager , Lodewijk A.A. Brosens , Quintus Molenaar , Bert A. Bonsing , Sven Mieog , Marc G. Besselink , Olivier R. Busch , Joanne Verheij , Arantza Farina Sarasqueta , Hanneke W. Wilmink , Jan Koster , Maarten F. Bijlsma , Henri H. Versteeg , Jeroen T. Buijs
{"title":"Tumor gene expression is associated with venous thromboembolism in patients with ductal pancreatic adenocarcinoma","authors":"Floris T.M. Bosch , Frederike Dijk , Saskia Briedé , Jesse V. Groen , Randa G. Hanna-Sawires , Hans Halfwerk , Frederikus A. Klok , Karin A.H. Kaasjager , Lodewijk A.A. Brosens , Quintus Molenaar , Bert A. Bonsing , Sven Mieog , Marc G. Besselink , Olivier R. Busch , Joanne Verheij , Arantza Farina Sarasqueta , Hanneke W. Wilmink , Jan Koster , Maarten F. Bijlsma , Henri H. Versteeg , Jeroen T. Buijs","doi":"10.1016/j.thromres.2024.109240","DOIUrl":"10.1016/j.thromres.2024.109240","url":null,"abstract":"<div><h3>Introduction</h3><div>In patients with pancreatic cancer, the risk of venous thromboembolism (VTE) is high compared to other cancer types, suggesting that tumor-intrinsic features drive hypercoagulability. Tumor gene expression analysis may help unravel the pathogenesis of VTE in these patients and help to identify high-risk patients.</div></div><div><h3>Aim</h3><div>To evaluate the association between tumor gene expression patterns and VTE in patients with pancreatic cancer.</div></div><div><h3>Methods</h3><div>In this retrospective cohort study RNA-sequence data from surgically resected tumor material from patients with pancreatic ductal adenocarcinoma (PDAC) was used to identify genes associated with the presence of venous thromboembolism (i.e., pulmonary embolism or deep-vein thrombosis) within one year follow-up after surgery. Additionally, VTE risk and expression of coagulation related genes in two molecular subtypes of pancreatic cancer was assessed.</div></div><div><h3>Results</h3><div>Out of 151 patients, 10 (6.6 %) developed deep-vein thrombosis or pulmonary embolism within one year follow-up. Differential expression analysis yielded 89 genes significantly differentially expressed in patients with VTE compared to those without VTE, including <em>ATP6V0A4</em>, <em>SYT14</em> and <em>ZNF114</em>. The incidence of VTE in classical subtype was higher (<em>n</em> = 9; 7.6 %) than in basal-like subtype (<em>n</em> = 1;4 %), but this difference was not statistically significant (SHR 1.79; 95 % CI 0.22–14.3). Forty-two coagulation-associated genes were identified that were differentially expressed between these molecular subtypes, including <em>F5</em>, <em>PLAU</em>, <em>SERPINE1</em>, and <em>C4BPB</em>.</div></div><div><h3>Conclusions</h3><div>Patients with pancreatic cancer and VTE show a different tumor gene expression profile than those without VTE. Multiple coagulation-related genes were differentially expressed in classical versus basal-like molecular subtype, suggesting that there is a difference in pro-thrombotic phenotype.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"246 ","pages":"Article 109240"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinhe Lin , Wenxing Li , Xin Zhang , Kai Zhou , Yanqi Yang , Shaoli Cheng , Ruifang Sun , Chengxue Dang , Dongmei Diao
{"title":"Thromboembolic events associated with immune checkpoint inhibitors in cancer patients: A Bayesian network meta-analysis","authors":"Jinhe Lin , Wenxing Li , Xin Zhang , Kai Zhou , Yanqi Yang , Shaoli Cheng , Ruifang Sun , Chengxue Dang , Dongmei Diao","doi":"10.1016/j.thromres.2024.109243","DOIUrl":"10.1016/j.thromres.2024.109243","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs), which offer previously unknown therapeutic advantages, have revolutionized cancer treatment. However, the risk of thromboembolic events (TEEs) associated with ICIs remains unclear. The aim of this network meta-analysis (NMA) was to evaluate the incidence of TEEs in cancer patients receiving different treatment regimens.</div></div><div><h3>Methods</h3><div>We searched for randomized clinical trials (RCTs) between January 2021 and December 2023 without restricting the cancer type. The percentages of TEEs were systematically extracted. An NMA was performed comparing atezolizumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, conventional therapy (which consists mainly of chemotherapy, targeted therapy, placebo, and their combinations), two ICI drugs, one ICI drug combined with conventional therapy, and two ICI drugs combined with conventional therapy. Additionally, subgroup analysis was conducted based on cancer type.</div></div><div><h3>Results</h3><div>Eighty-three RCTs involving 54,736 patients were included. Patients receiving ICIs demonstrated comparable risks of arterial thromboembolism (ATE), deep vein thrombosis (DVT), myocardial infarction (MI), and cerebrovascular accidents (CVAs). Nivolumab (OR 0.39, 95 % CI 0.19 to 0.80) and two ICI drugs (OR 0.52, 95 % CI 0.29 to 0.89) had the lowest risk of venous thromboembolism (VTE) compared to two ICI drugs with conventional therapy. The risk of pulmonary embolism (PE) was greater for ipilimumab (OR 4.09, 95 % CI 1.13 to 15.51) than for nivolumab. For melanoma in the subgroup analysis, nivolumab significantly reduced the risk of VTE (OR 0.07, 95 % CI 0.00 to 0.76) compared to two ICI drugs. Among the single-ICI regimens, durvalumab was associated with the highest incidence of ATE, MI, and CVAs; ipilimumab had the highest incidence of VTE and PE; and pembrolizumab had the highest incidence of DVT. The combination of one ICI drug with conventional therapy was associated with a significantly greater risk of TEEs (except for MI) than the combination of two ICI drugs.</div></div><div><h3>Conclusions</h3><div>Various ICI regimens in cancer patients exhibit clinically significant differences in the risks of TEEs. Nivolumab exhibited a favorable safety profile regarding VTE, while ipilimumab had the highest risk of both VTE and PE. Different ICI regimens require tailored risk management strategies to reduce TEEs.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"246 ","pages":"Article 109243"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pre-infection anticoagulant exposure and SARS-CoV-2 infection outcomes – Differential mortality by age","authors":"Itshak Amsalem , Asher Shafrir , Yosef Kalish , Ora Paltiel","doi":"10.1016/j.thromres.2025.109254","DOIUrl":"10.1016/j.thromres.2025.109254","url":null,"abstract":"<div><h3>Background</h3><div>The risk of thrombosis increases after SARS-CoV-2 infection. This study aimed to assess associations between pre-infection anticoagulant exposure and SARS-CoV-2 infection-related outcomes in a population-based cohort.</div></div><div><h3>Methods</h3><div>Members of the “Meuhedet” health maintenance organization aged >45 years who tested positive for SARS-CoV-2 infection (03/2020–04/2022) were followed. Pre-infection anticoagulant exposure (PAE) was defined as any anticoagulant therapy prescribed ≥1 month prior to SARS-CoV-2 testing. Univariate analyses, multivariable models adjusting for confounders, propensity-score matching, and an age-stratified analysis were performed to assess associations between PAE and hospitalization, intensive care unit (ICU) admission, 30-day and one-year mortality.</div></div><div><h3>Results</h3><div>Of the 127,801 patients included, 2951(2.3 %) had PAE. Comorbidities including ischemic heart disease, diabetes mellitus, hypertension, heart failure, and atrial fibrillation were more common among anticoagulant-exposed than unexposed individuals (<em>p</em> < 0.001).</div><div>Patients with PAE experienced higher hospitalization (22.7 % vs 5.6 %), ICU admissions (1.9 % vs 0.5 %), 30-day and 1-year mortality rates (4.8 % vs. 0.6, and 8.8 % vs. 1.1 %, respectively), than unexposed individuals, but similar lengths-of-stay. In the multivariable analysis, PAE was independently associated only with hospitalizations (adjusted odds ratio (aOR) = 1.29 [95 % confidence interval (CI): 1.13–1.47]), whereas in the propensity-matched analysis, none of the outcomes differed significantly between the groups.</div><div>However, in the stratum aged >75 years, 30-day and one-year mortality were significantly reduced in those with PAE (aOR = 0.68 [CI:0.48–0.97], and aOR = 0.73 [CI:0.55–0.97], respectively).</div></div><div><h3>Conclusion</h3><div>SARS-CoV-2-infected individuals with prior exposure to anticoagulants have more comorbidities and experienced a higher incidence of hospitalization but not mortality compared to unexposed patients. Paradoxically, mortality risks decreased in the oldest stratum of anticoagulant-exposed individuals. Further research is required to assess mechanisms for this apparent protective effect.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"246 ","pages":"Article 109254"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972163","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}
M.P. Ward , E.M. Ibrahim , S.A. O'Toole , Z. Marchocki , J.J. O'Leary , F. Abu Saadeh , L.A. Norris
{"title":"Chemotherapy alters thrombomodulin and factor VIIIc expression resulting in acquired activated protein C resistance and enhanced thrombin generation in cancer associated thrombosis","authors":"M.P. Ward , E.M. Ibrahim , S.A. O'Toole , Z. Marchocki , J.J. O'Leary , F. Abu Saadeh , L.A. Norris","doi":"10.1016/j.thromres.2024.109251","DOIUrl":"10.1016/j.thromres.2024.109251","url":null,"abstract":"<div><h3>Background</h3><div>Tumour type, treatment and patient related factors contribute to cancer associated venous thromboembolism (VTE), however, the role of each factor and the mechanisms involved are not understood.</div></div><div><h3>Aim</h3><div>To assess the role of the tumour, and of chemotherapy, in mediating the procoagulant response associated with VTE in gynaecological cancer patients.</div></div><div><h3>Methods</h3><div>Gynaecological cancer patients who developed VTE during follow-up (<em>n</em> = 59) (VTE+) were matched with treatment naïve(treatment (−)(VTE-)(<em>n</em> = 120) and chemotherapy treated patients(treatment (+)(VTE-) (<em>n</em> = 57)). Thrombin generation, Factor V(FV), VIIIc(FVIIIc), Tissue Factor Pathway Inhibitor(TFPI), soluble Thrombomodulin(sTM), Protein S(PS), C(PC) endothelial protein C receptor(EPCR) and fibrinogen were compared in each group. EPCR and TM expression was assessed in EA.hy926 cells in vitro following addition of chemotherapy agents. mRNA expression of coagulation genes was measured in tumour biopsies.</div></div><div><h3>Results</h3><div>Thrombin generation was increased in treatment(−)VTE(+) compared with treatment(−)VTE(−) controls but not in the treatment(+)VTE(+) patients. Using the TM modified assay, thrombin generation was increased in the treatment (+)VTE(−) group compared with treatment(−)(VTE-) with a further increase in the treatment (+) VTE(+) group. Reduced levels of sTM in treatment (+) VTE(+) patients correlated with thrombin generation. TM expression was reduced in vitro by carboplatin and paclitaxel. FVIIIc was increased in both VTE groups and was predictive of VTE. <em>F5</em> mRNA levels were lower in tumours from VTE(+) patients compared with controls.</div></div><div><h3>Conclusion</h3><div>Chemotherapy alters sTM and confers an acquired activated Protein C(aPC) resistance which may be implicated in cancer associated VTE in gynaecological cancer patients. FVIIIc may be a useful predictive marker for VTE in cancer patients in this setting.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"246 ","pages":"Article 109251"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jieming Huang , Yiming Li , Yueping Li , Qianwen Yu , Xiaochun Chen , Qinyong Ye , Ying Chen
{"title":"A new hereditary PROS1 gene mutation caused isolated cortical venous thrombosis","authors":"Jieming Huang , Yiming Li , Yueping Li , Qianwen Yu , Xiaochun Chen , Qinyong Ye , Ying Chen","doi":"10.1016/j.thromres.2025.109252","DOIUrl":"10.1016/j.thromres.2025.109252","url":null,"abstract":"<div><h3>Background</h3><div>Protein S deficiency is a rare inherited disease. We report the case of a young man who unexpectedly developed isolated cortical vein thrombosis (ICoVT) associated with a novel PROS1 mutation.</div></div><div><h3>Methods</h3><div>Clinical symptoms were recorded, and physical examinations conducted. Comprehensive laboratory tests included routine coagulation function tests, protein C activity, and antithrombin III levels. Advanced imaging techniques, such as magnetic resonance imaging (MRI), magnetic resonance venography (MRV), and computed tomography angiography (CTA) were employed. We also performed genetic analysis on the patient and his parents.</div></div><div><h3>Results</h3><div>The patient presented with headaches and paroxysmal convulsions without identifiable triggers. Physical examinations and routine coagulation tests were generally normal, except for a markedly reduced protein S activity at 21.2 %. MRI scans revealed right parietal cerebral hemorrhage and thickening of the cortical vein, characterized by high T1-weighted Imaging and low T2-weighted Imaging and Fluid-Attenuated Inversion Recovery signals. CTA and Doppler ultrasound of the lower limbs showed no abnormalities. Family history revealed that his father had suffered from multiple venous thromboses. Genetic testing identified a missense mutation (c.1912G>T p.Gly638Cys) in both the patient and his father, along with a duplication of approximately 403.6 kb on chromosome 3q26.32-33 in the patient.</div></div><div><h3>Conclusions</h3><div>This case highlights a novel PROS1 missense mutation and its significant role in development of cortical venous thrombosis. It provides a new insight into the genetic basis of autosomal dominant thrombophilia associated with protein S deficiency (THPH5).</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"246 ","pages":"Article 109252"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}