Pub Date : 2025-02-15DOI: 10.1016/j.thromres.2025.109286
Yuko Mishima , Hisako Okada , Amir L. Butt , Kenneth E. Stewart , Michael A. Mazzeffi , Kenichi A. Tanaka
{"title":"In vitro procoagulant effects of Gla-domainless factor Xa in factor XI-deficient and factor IX-deficient plasma","authors":"Yuko Mishima , Hisako Okada , Amir L. Butt , Kenneth E. Stewart , Michael A. Mazzeffi , Kenichi A. Tanaka","doi":"10.1016/j.thromres.2025.109286","DOIUrl":"10.1016/j.thromres.2025.109286","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"247 ","pages":"Article 109286"},"PeriodicalIF":3.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428789","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 : 2025-02-14DOI: 10.1016/j.thromres.2025.109284
Tzu-Fei Wang , Suhong Luo , Brian F. Gage , Martin W. Schoen , Amber Afzal , Kenneth Carson , Su-Hsin Chang , Amir Mahmoud , Kristen M. Sanfilippo
Introduction
Patients with hematological malignancies are at an increased risk of severe bleeding. Anticoagulant (AC) therapy further increases this risk. Mortality after these bleeds is unclear and may differ by bleeding site.
Aim
To evaluate the association between bleeding and mortality in patients with hematological malignancies prescribed AC therapy for cancer-associated venous thromboembolism (VTE).
Methods
In a nationwide cohort of US Veterans (2012−2020), we identified patients with hematological malignancies and cancer-associated VTE prescribed AC therapy. Bleeding events were identified by a previously validated algorithm using hospitalization International Classification of Disease (ICD) codes. Within 12 months of AC therapy initiation, we evaluated the association between bleeding and mortality using multivariate Cox regression models, with AC-related bleeding analyzed as a time-varying covariate.
Results
The cohort included 1825 patients. Within 12 months of starting AC therapy, 123 (6.7 %) had bleeding events and 162 (8.9 %) patients died. Patients with bleeding events were more likely to have anemia, history of bleeding, aspirin use, chemotherapy use, and frailty. A multivariable Cox proportional-hazard model showed that AC-related bleeding was associated with tripled mortality rate (aHR 3.26, 95 % CI 1.96–5.45). When stratified by bleeding site, intracranial bleeding was associated with the highest risk of death (aHR 13.41, 95 % CI 4.13–43.48), followed by gastrointestinal bleeding (aHR 4.55, 95 % CI 2.48–8.35).
Conclusion
In this cohort of patients with hematological malignancies and newly diagnosed VTE initiated on AC therapy, bleeding was associated with an increased risk of mortality within 12 months. Association was highest with intracranial and gastrointestinal bleeding.
{"title":"Association between anticoagulant-related bleeding and mortality in patients with hematological malignancies and cancer-associated venous thromboembolism","authors":"Tzu-Fei Wang , Suhong Luo , Brian F. Gage , Martin W. Schoen , Amber Afzal , Kenneth Carson , Su-Hsin Chang , Amir Mahmoud , Kristen M. Sanfilippo","doi":"10.1016/j.thromres.2025.109284","DOIUrl":"10.1016/j.thromres.2025.109284","url":null,"abstract":"<div><h3>Introduction</h3><div>Patients with hematological malignancies are at an increased risk of severe bleeding. Anticoagulant (AC) therapy further increases this risk. Mortality after these bleeds is unclear and may differ by bleeding site.</div><div>Aim</div><div>To evaluate the association between bleeding and mortality in patients with hematological malignancies prescribed AC therapy for cancer-associated venous thromboembolism (VTE).</div></div><div><h3>Methods</h3><div>In a nationwide cohort of US Veterans (2012−2020), we identified patients with hematological malignancies and cancer-associated VTE prescribed AC therapy. Bleeding events were identified by a previously validated algorithm using hospitalization International Classification of Disease (ICD) codes. Within 12 months of AC therapy initiation, we evaluated the association between bleeding and mortality using multivariate Cox regression models, with AC-related bleeding analyzed as a time-varying covariate.</div></div><div><h3>Results</h3><div>The cohort included 1825 patients. Within 12 months of starting AC therapy, 123 (6.7 %) had bleeding events and 162 (8.9 %) patients died. Patients with bleeding events were more likely to have anemia, history of bleeding, aspirin use, chemotherapy use, and frailty. A multivariable Cox proportional-hazard model showed that AC-related bleeding was associated with tripled mortality rate (aHR 3.26, 95 % CI 1.96–5.45). When stratified by bleeding site, intracranial bleeding was associated with the highest risk of death (aHR 13.41, 95 % CI 4.13–43.48), followed by gastrointestinal bleeding (aHR 4.55, 95 % CI 2.48–8.35).</div></div><div><h3>Conclusion</h3><div>In this cohort of patients with hematological malignancies and newly diagnosed VTE initiated on AC therapy, bleeding was associated with an increased risk of mortality within 12 months. Association was highest with intracranial and gastrointestinal bleeding.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"248 ","pages":"Article 109284"},"PeriodicalIF":3.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437726","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 : 2025-02-13DOI: 10.1016/j.thromres.2025.109285
Rafaela Vostatek , Marina Trappl , Cornelia Englisch , Philipp Hohensinner , Matthias Preusser , Ingrid Pabinger , Cihan Ay
Venous thromboembolism (VTE) is a common and serious complication among cancer patients. Mitochondrial DNA (mtDNA) copy number is known to influence various cellular pathways involved in cancer development. While an association between reduced mtDNA and VTE risk in non-cancer patients was previously reported, its relationship with VTE in cancer patients remains unclear.
Therefore, we aimed to investigate the association between mtDNA copy number and VTE risk in a nested-case control study of 48 patients from the Vienna Cancer and Thrombosis Study (CATS), a prospective observational cohort study. The mtDNA copy number was measured in equally distributed age, sex, cancer type, and stage matched patients with and without VTE using a qPCR-based method.
Of the 48 patients, 24 were diagnosed with VTE (median age [IQR] 62 [57–60] years, 54.2 % female) and 24 had no VTE event (median age [IQR] 63 [58–71] years, 54.2 % female). We found that patients who developed VTE had lower mtDNA copy numbers compared to those without VTE (216.73 [167.99–401.39] vs 301.47 [210.66–526.84]). Multivariable analysis adjusting for chronological age, D-dimer, sex, cancer stage and BMI revealed that each 10-unit increase in mtDNA copy number decreased the odds of VTE occurrence by 5.9 % (p = 0.021). Patients with distant metastatic cancer (M1) had lower mtDNA copy numbers than those without distant metastasis at study inclusion (220.34 [172.67–323.70] vs 328.48 [213.89–556.68; p = 0.052).
Overall, our findings suggest a potential link between reduced mtDNA copy number and increased VTE risk in cancer patients.
{"title":"Mitochondrial DNA copy number and its association with venous thromboembolism in patients with cancer","authors":"Rafaela Vostatek , Marina Trappl , Cornelia Englisch , Philipp Hohensinner , Matthias Preusser , Ingrid Pabinger , Cihan Ay","doi":"10.1016/j.thromres.2025.109285","DOIUrl":"10.1016/j.thromres.2025.109285","url":null,"abstract":"<div><div>Venous thromboembolism (VTE) is a common and serious complication among cancer patients. Mitochondrial DNA (mtDNA) copy number is known to influence various cellular pathways involved in cancer development. While an association between reduced mtDNA and VTE risk in non-cancer patients was previously reported, its relationship with VTE in cancer patients remains unclear.</div><div>Therefore, we aimed to investigate the association between mtDNA copy number and VTE risk in a nested-case control study of 48 patients from the Vienna Cancer and Thrombosis Study (CATS), a prospective observational cohort study. The mtDNA copy number was measured in equally distributed age, sex, cancer type, and stage matched patients with and without VTE using a qPCR-based method.</div><div>Of the 48 patients, 24 were diagnosed with VTE (median age [IQR] 62 [57–60] years, 54.2 % female) and 24 had no VTE event (median age [IQR] 63 [58–71] years, 54.2 % female). We found that patients who developed VTE had lower mtDNA copy numbers compared to those without VTE (216.73 [167.99–401.39] vs 301.47 [210.66–526.84]). Multivariable analysis adjusting for chronological age, D-dimer, sex, cancer stage and BMI revealed that each 10-unit increase in mtDNA copy number decreased the odds of VTE occurrence by 5.9 % (<em>p</em> = 0.021). Patients with distant metastatic cancer (M1) had lower mtDNA copy numbers than those without distant metastasis at study inclusion (220.34 [172.67–323.70] vs 328.48 [213.89–556.68; <em>p</em> = 0.052).</div><div>Overall, our findings suggest a potential link between reduced mtDNA copy number and increased VTE risk in cancer patients.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"248 ","pages":"Article 109285"},"PeriodicalIF":3.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428999","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}
Acquired factor XI (FXI) deficiency of autoimmune origin is a rare condition, with only a few cases in children having been documented in the literature. In this study, we present a series of four pediatric patients from France who have been diagnosed with FXI deficiency of autoimmune origin and review four cases from the literature. The majority of patients were adolescents, and many had associated autoimmune disorders. The bleeding symptoms manifested as mild or non-existent, and despite the anticipated hemorrhagic phenotype, two patients exhibited thrombotic episodes, one of which was associated with the administration of prophylactic treatment with activated factor VII.
{"title":"Acquired factor XI deficiency in paediatrics patients: A French series and review of literature cases","authors":"Julie Avoine , Annie Harroche , Saba Azarnoush , Yoann Huguenin , Adeline Blandinieres , Emanuelle De Raucourt , Caroline Galeotti , Alexandre Theron","doi":"10.1016/j.thromres.2025.109282","DOIUrl":"10.1016/j.thromres.2025.109282","url":null,"abstract":"<div><div>Acquired factor XI (FXI) deficiency of autoimmune origin is a rare condition, with only a few cases in children having been documented in the literature. In this study, we present a series of four pediatric patients from France who have been diagnosed with FXI deficiency of autoimmune origin and review four cases from the literature. The majority of patients were adolescents, and many had associated autoimmune disorders. The bleeding symptoms manifested as mild or non-existent, and despite the anticipated hemorrhagic phenotype, two patients exhibited thrombotic episodes, one of which was associated with the administration of prophylactic treatment with activated factor VII.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"247 ","pages":"Article 109282"},"PeriodicalIF":3.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387348","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 : 2025-02-07DOI: 10.1016/j.thromres.2025.109279
Robert J. Trager , Catherine P. Haering , Anthony N. Baumann , Debbie S. Wright
Background
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).
Methods
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).
Results
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]; P = 0.0195). A similar association was observed for stroke (COCs: 0.106 %, IUDs: 0.057 %; RR = 1.86 [1.49,2.32]; P < 0.0001). The secondary COC2 analysis revealed similar findings.
Conclusions
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.
{"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}
Pub Date : 2025-02-05DOI: 10.1016/j.thromres.2025.109283
Aya Takemoto , Nobuyo Kondo , Akiko Kitajo , Hiroto Yamamoto , Yudai Yamamoto , Koji Higashino , Tokujiro Uchida
Background
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.
Methods
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.
Results
The DBCM coagulation time correlated with plasma factor Xa inhibitor concentrations (Rs = 0.87 for apixaban [n = 57, P < 0.001]; Rs = 0.91 for rivaroxaban [n = 49, P < 0.001]) and peak thrombin generation (Rs = −0.80 for apixaban [n = 57, P < 0.001]; Rs = −0.84 for rivaroxaban [n = 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.
Conclusions
DBCM was a useful point-of-care test to evaluate the anticoagulation effect induced by factor Xa inhibitors.
{"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}
Pub Date : 2025-02-04DOI: 10.1016/j.thromres.2025.109280
C. Farkh , P.H. Wicky , A. Perrier-Cornet , M. Koskas , N. Ajzenberg , D. Faille
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.
{"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}
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.
Methods
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.
Results
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.
Conclusion
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.
{"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}
Pub Date : 2025-02-03DOI: 10.1016/j.thromres.2025.109278
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}
Pub Date : 2025-02-01DOI: 10.1016/j.thromres.2024.109240
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
Introduction
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.
Aim
To evaluate the association between tumor gene expression patterns and VTE in patients with pancreatic cancer.
Methods
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.
Results
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 ATP6V0A4, SYT14 and ZNF114. The incidence of VTE in classical subtype was higher (n = 9; 7.6 %) than in basal-like subtype (n = 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 F5, PLAU, SERPINE1, and C4BPB.
Conclusions
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.
在胰腺癌患者中,与其他类型的癌症相比,静脉血栓栓塞(VTE)的风险较高,这表明肿瘤固有特征驱动高凝。肿瘤基因表达分析可能有助于揭示这些患者静脉血栓栓塞的发病机制,并有助于识别高危患者。目的:探讨胰腺癌患者肿瘤基因表达模式与静脉血栓栓塞的关系。方法:在这项回顾性队列研究中,来自胰腺导管腺癌(PDAC)患者手术切除肿瘤材料的rna序列数据被用于在手术后一年内确定与静脉血栓栓塞(即肺栓塞或深静脉血栓形成)存在相关的基因。此外,还评估了两种分子亚型胰腺癌的血栓栓塞风险和凝血相关基因的表达。结果:151例患者中,10例(6.6%)在随访1年内发生深静脉血栓形成或肺栓塞。差异表达分析发现,VTE患者与非VTE患者有89个基因显著表达差异,包括ATP6V0A4、SYT14和ZNF114。经典亚型静脉血栓栓塞发生率较高(n = 9;7.6%)高于基底样亚型(n = 1; 4%),但差异无统计学意义(SHR 1.79;95% ci 0.22-14.3)。42个凝血相关基因在这些分子亚型之间存在差异表达,包括F5、PLAU、SERPINE1和C4BPB。结论:胰腺癌合并静脉血栓栓塞患者的肿瘤基因表达谱与未合并静脉血栓栓塞患者不同。多种凝血相关基因在经典和基底样分子亚型中表达差异,表明促血栓表型存在差异。
{"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}