Pub Date : 2026-01-15DOI: 10.1016/j.thromres.2026.109590
Thaís D.R. Nóbrega , Tiago Boechat , Denys E. Fujimoto , Sibia S. Marcondes , Silvia Bueno , Suzanna A. Tavares , Alessandra Prezotti , Juliana S.M. Duarte , Fabiana C.C. Piassi , Lucas Cesped , Erica Okazaki , Bianca Stefanello , Carolina Costa-Lima , Paula R. Villaça , Fernanda A. Orsi
Most data supporting current knowledge about thrombotic thrombocytopenic purpura (TTP) come from high-income regions, while little is known about treatment access and prognosis in low- and middle-income countries. To address this gap, we conducted a multicenter prospective study that included 85 TTP patients in Brazil between 2018 and 2024, with a 12-month follow-up. The median age was 37 years (IQR 27–45) and 76% were female. The median PLASMIC score was six (IQR 6.0–7.0), and ADAMTS13 activity was tested in 62.4% of patients (all <10%). The median time from symptom onset to hospital admission was 8 days. Neurological manifestations were the most frequent (75.3%), followed by bleeding symptoms (58.8%) and abdominal pain (32.9%). Seventy-four patients (87.1%) underwent therapeutic plasma exchange (TPE), which was initiated within one day of admission (IQR 1–2). Corticosteroids were administered in 95.3% and rituximab in 56.5% of patients. Twenty-three patients (27.1%) required advanced life support and 13 (15.3%) died during hospitalization. In-hospital mortality was associated with older age and hemodynamic instability upon admission. Among survivors, 26% experienced exacerbation or relapse, and 22.4% developed chronic sequelae, mostly neurological and psychiatric symptoms. Rituximab use was protective against TTP relapses. In conclusion, TTP mortality in Brazil is higher than that observed in recent cohorts. TTP diagnosis and treatment in the country are delayed and outdated, negatively affecting disease prognosis. Ensuring rapid diagnosis and the availability of TPE and rituximab, a cost-effective treatment strategy, is essential for improving outcomes and reducing morbidity, including in low- and middle-income countries.
{"title":"Brazilian Registry of Thrombotic Thrombocytopenic Purpura: A prospective cohort study of diagnosis, management and outcomes in Brazil","authors":"Thaís D.R. Nóbrega , Tiago Boechat , Denys E. Fujimoto , Sibia S. Marcondes , Silvia Bueno , Suzanna A. Tavares , Alessandra Prezotti , Juliana S.M. Duarte , Fabiana C.C. Piassi , Lucas Cesped , Erica Okazaki , Bianca Stefanello , Carolina Costa-Lima , Paula R. Villaça , Fernanda A. Orsi","doi":"10.1016/j.thromres.2026.109590","DOIUrl":"10.1016/j.thromres.2026.109590","url":null,"abstract":"<div><div>Most data supporting current knowledge about thrombotic thrombocytopenic purpura (TTP) come from high-income regions, while little is known about treatment access and prognosis in low- and middle-income countries. To address this gap, we conducted a multicenter prospective study that included 85 TTP patients in Brazil between 2018 and 2024, with a 12-month follow-up. The median age was 37 years (IQR 27–45) and 76% were female. The median PLASMIC score was six (IQR 6.0–7.0), and ADAMTS13 activity was tested in 62.4% of patients (all <10%). The median time from symptom onset to hospital admission was 8 days. Neurological manifestations were the most frequent (75.3%), followed by bleeding symptoms (58.8%) and abdominal pain (32.9%). Seventy-four patients (87.1%) underwent therapeutic plasma exchange (TPE), which was initiated within one day of admission (IQR 1–2). Corticosteroids were administered in 95.3% and rituximab in 56.5% of patients. Twenty-three patients (27.1%) required advanced life support and 13 (15.3%) died during hospitalization. In-hospital mortality was associated with older age and hemodynamic instability upon admission. Among survivors, 26% experienced exacerbation or relapse, and 22.4% developed chronic sequelae, mostly neurological and psychiatric symptoms. Rituximab use was protective against TTP relapses. In conclusion, TTP mortality in Brazil is higher than that observed in recent cohorts. TTP diagnosis and treatment in the country are delayed and outdated, negatively affecting disease prognosis. Ensuring rapid diagnosis and the availability of TPE and rituximab, a cost-effective treatment strategy, is essential for improving outcomes and reducing morbidity, including in low- and middle-income countries.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"258 ","pages":"Article 109590"},"PeriodicalIF":3.4,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977993","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 : 2026-01-12DOI: 10.1016/j.thromres.2026.109587
Dongyue Fan , Vincent Lanting , Eleonora Camilleri , Mettine H.A. Bos , Araci M.R. Rondon , Henri H. Versteeg
Background
Patients with gastrointestinal (GI) cancer are at increased risk of venous thromboembolism (VTE), which is an important cause of mortality. Risk stratification of VTE in GI cancer remains challenging.
Objectives
To investigate whether assessment of the coagulation system can predict VTE risk in three GI tumor types.
Methods
We used a nested case-control design within the MICA cohort (total N = 81), including 27 patients who developed VTE during follow-up and 54 matched non-VTE controls. The subgroup distribution was esophageal cancer (n = 42), pancreatic cancer (n = 18), and colorectal cancer (n = 21). Plasma samples were analyzed using a multifaceted approach incorporating tissue factor (TF) measurement, thrombin generation, and endothelial function testing within an artificial vessel model. Conditional logistic regression was used to evaluate associations between coagulation parameters and VTE risk.
Results
TF concentrations did not differ between patients with and without VTE across esophageal, colorectal, and pancreatic cancers. In esophageal cancer, prolonged lag time, as well as higher endogenous thrombin potential and peak values in the artificial vessel model, were significantly associated with an increased risk of VTE (OR = 9.95, 95% CI 1.21–81.54; OR = 5.15, 95% CI 1.07–25.00; OR = 10.75, 95% CI 1.31–90.91). No significant differences in coagulation-related parameters were observed in pancreatic or colorectal cancer patients.
Conclusion
Abnormal coagulation may be associated with VTE risk mainly in esophageal cancer, suggesting that VTE biomarkers may differ by cancer type and require further investigation in larger cohorts.
胃肠道（GI）癌症患者发生静脉血栓栓塞（VTE）的风险增加，这是导致死亡的一个重要原因。静脉血栓栓塞在胃肠道癌症中的风险分层仍然具有挑战性。目的探讨凝血系统的评估是否能预测三种消化道肿瘤类型的静脉血栓栓塞风险。方法在MICA队列中采用嵌套病例-对照设计（总N = 81），包括27例在随访期间发生静脉血栓栓塞的患者和54例匹配的非静脉血栓栓塞对照组。亚组分布为食管癌（n = 42）、胰腺癌（n = 18）、结直肠癌（n = 21）。血浆样本分析使用多方面的方法结合组织因子（TF）测量，凝血酶的产生，和内皮功能测试在人工血管模型。使用条件逻辑回归来评估凝血参数与静脉血栓栓塞风险之间的关系。结果食管癌、结直肠癌和胰腺癌患者与非VTE患者之间的stf浓度无差异。在食管癌中，人工血管模型中延迟时间延长、内源性凝血酶电位和峰值升高与VTE风险增加显著相关（OR = 9.95, 95% CI 1.21-81.54; OR = 5.15, 95% CI 1.07-25.00; OR = 10.75, 95% CI 1.31-90.91）。胰腺癌和结直肠癌患者的凝血相关参数无显著差异。结论凝血异常可能主要与食管癌的静脉血栓栓塞风险相关，提示静脉血栓栓塞生物标志物可能因癌症类型而异，需要在更大的队列中进一步研究。
{"title":"Coagulation parameters in gastrointestinal cancer patients with venous thromboembolism","authors":"Dongyue Fan , Vincent Lanting , Eleonora Camilleri , Mettine H.A. Bos , Araci M.R. Rondon , Henri H. Versteeg","doi":"10.1016/j.thromres.2026.109587","DOIUrl":"10.1016/j.thromres.2026.109587","url":null,"abstract":"<div><h3>Background</h3><div>Patients with gastrointestinal (GI) cancer are at increased risk of venous thromboembolism (VTE), which is an important cause of mortality. Risk stratification of VTE in GI cancer remains challenging.</div></div><div><h3>Objectives</h3><div>To investigate whether assessment of the coagulation system can predict VTE risk in three GI tumor types.</div></div><div><h3>Methods</h3><div>We used a nested case-control design within the MICA cohort (total <em>N</em> = 81), including 27 patients who developed VTE during follow-up and 54 matched non-VTE controls. The subgroup distribution was esophageal cancer (<em>n</em> = 42), pancreatic cancer (<em>n</em> = 18), and colorectal cancer (<em>n</em> = 21). Plasma samples were analyzed using a multifaceted approach incorporating tissue factor (TF) measurement, thrombin generation, and endothelial function testing within an artificial vessel model. Conditional logistic regression was used to evaluate associations between coagulation parameters and VTE risk.</div></div><div><h3>Results</h3><div>TF concentrations did not differ between patients with and without VTE across esophageal, colorectal, and pancreatic cancers. In esophageal cancer, prolonged lag time, as well as higher endogenous thrombin potential and peak values in the artificial vessel model, were significantly associated with an increased risk of VTE (OR = 9.95, 95% CI 1.21–81.54; OR = 5.15, 95% CI 1.07–25.00; OR = 10.75, 95% CI 1.31–90.91). No significant differences in coagulation-related parameters were observed in pancreatic or colorectal cancer patients.</div></div><div><h3>Conclusion</h3><div>Abnormal coagulation may be associated with VTE risk mainly in esophageal cancer, suggesting that VTE biomarkers may differ by cancer type and require further investigation in larger cohorts.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"258 ","pages":"Article 109587"},"PeriodicalIF":3.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979148","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 : 2026-01-12DOI: 10.1016/j.thromres.2026.109585
Alexandra C. Frost , Veysel K. Baris , Michael Sainlaire , Jin Chen , Minakshi V. Shukla , Md Shifatul A. Apurba , Ann C. Hurley , Patricia C. Dykes
Introduction
Delayed diagnosis (DDx) of Venous thromboembolism (VTE) contributes to preventable mortality. Our prior work resulted in an electronic Clinical Quality Measure (eCQM) for Diagnostic Delay of VTE (DOVE) [1] and a phenotyping algorithm to identify cases of VTE [2]. Current work incorporates voices of VTE survivors to extend that research.
Methods
We interviewed 8 and surveyed 68 VTE survivors, coded and categorized text, and uploaded data into the DOVE qualitative database. Drawing on this database and patient self-management literature, notably the concepts: patient engagement [3,4] and patient activation [5,6] we developed a model to guide “Successful Living with VTE.”
Results
The 76 VTE survivors provided rich descriptions of their journeys from questioning that something may be wrong to making recommendations to help others. Participants were articulate, highly educated, mostly female and white, and geographically diverse. Recommendations were defined as “Recommendations for patients, providers and health care sites targeted to achieve timely VTE diagnosis and treatment across the trajectory from first concern through follow-up care.” Patients are advised to be assertive, obtain education and bring a support person. Providers are advised to listen, be knowledgeable and consider genetic testing.
Conclusions
The recommendations make common sense, do not require expensive equipment or intensive training or extra staff. VTE survivors' recommendations merged with the science of patient self-management provided the model's structure. The model will inform a VTE curriculum and clinical decision support application, and guide research to promote successful living with VTE.
{"title":"A model to guide successful living with venous thromboembolism (VTE): Recommendations derived from the qualitative phase of a study of diagnostic Delay of VTE (DOVE)","authors":"Alexandra C. Frost , Veysel K. Baris , Michael Sainlaire , Jin Chen , Minakshi V. Shukla , Md Shifatul A. Apurba , Ann C. Hurley , Patricia C. Dykes","doi":"10.1016/j.thromres.2026.109585","DOIUrl":"10.1016/j.thromres.2026.109585","url":null,"abstract":"<div><h3>Introduction</h3><div><u>D</u>elayed <u>d</u>iagnosis (DDx) of <u>V</u>enous <u>t</u>hrombo<u>e</u>mbolism (VTE) contributes to preventable mortality. Our prior work resulted in an electronic Clinical Quality Measure (eCQM) for Diagnostic <u>D</u>elay <u>o</u>f <u>V</u>T<u>E</u> (DOVE) [1] and a phenotyping algorithm to identify cases of VTE [2]. Current work incorporates voices of VTE survivors to extend that research.</div></div><div><h3>Methods</h3><div>We interviewed 8 and surveyed 68 VTE survivors, coded and categorized text, and uploaded data into the DOVE qualitative database. Drawing on this database and patient self-management literature, notably the concepts: patient engagement [3,4] and patient activation [5,6] we developed a model to guide “Successful Living with VTE.”</div></div><div><h3>Results</h3><div>The 76 VTE survivors provided rich descriptions of their journeys from questioning that something may be wrong to making recommendations to help others. Participants were articulate, highly educated, mostly female and white, and geographically diverse. Recommendations were defined as “Recommendations for patients, providers and health care sites targeted to achieve timely VTE diagnosis and treatment across the trajectory from first concern through follow-up care.” Patients are advised to <u>be assertive</u>, <u>obtain education</u> and <u>bring a support person</u>. Providers are advised to l<u>isten</u>, <u>be knowledgeable</u> and <u>consider genetic testing</u>.</div></div><div><h3>Conclusions</h3><div>The recommendations make common sense, do not require expensive equipment or intensive training or extra staff. VTE survivors' recommendations merged with the science of patient self-management provided the model's structure. The model will inform a VTE curriculum and clinical decision support application, and guide research to promote successful living with VTE.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"258 ","pages":"Article 109585"},"PeriodicalIF":3.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977995","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 : 2026-01-10DOI: 10.1016/j.thromres.2026.109584
Fengting Yuan , Huan Zhang , Dong Zhang , Xiong Zhao , Qiang Wang , Junting Jia , Rui Wang , Zhenpeng Fu , Linsheng Zhan , Jingang Zhang , Fang Yuan , Yuyuan Ma
Internal hemorrhage remains a critical challenge requiring immediate intervention. Recent advances in biomaterials have positioned fibrin hemostatic patches (FHPs) as a promising therapeutic option through targeted fibrinogen-to-fibrin conversion at the injured organ; however, insufficient understanding of the stoichiometric coupling between active components of FHP may limit its coagulation performance. Here, we report a novel FHP (nFHP) through orthogonal optimization of fibrinogen, thrombin, and calcium chloride. Systematic screening identified fibrinogen concentration as the primary determinant of clotting time, with fibrinogen-to-thrombin and fibrinogen-to-calcium chloride ratios further impacting. nFHP, fabricated with the optimal formulation (17 mg/cm2 fibrinogen, 40 IU/cm2 thrombin, 115 μg/cm2 calcium chloride), achieved rapid fibrin network formation and superior adhesive strength on the porcine aorta, surpassing commercial FHP (cFHP). In vivo evaluations across hepatic resection, cardiac stab wound, and arterial hemorrhage models demonstrated nFHP's universal efficacy, achieving the minimal blood loss compared to commercial products. Our work identifies stoichiometric proportion as a key factor in fibrin-based biomaterial rational design and provides a translatable solution for uncontrolled internal hemorrhage.
{"title":"Enhanced efficacy of fibrin hemostatic patch through rational design at the molecular level","authors":"Fengting Yuan , Huan Zhang , Dong Zhang , Xiong Zhao , Qiang Wang , Junting Jia , Rui Wang , Zhenpeng Fu , Linsheng Zhan , Jingang Zhang , Fang Yuan , Yuyuan Ma","doi":"10.1016/j.thromres.2026.109584","DOIUrl":"10.1016/j.thromres.2026.109584","url":null,"abstract":"<div><div>Internal hemorrhage remains a critical challenge requiring immediate intervention. Recent advances in biomaterials have positioned fibrin hemostatic patches (FHPs) as a promising therapeutic option through targeted fibrinogen-to-fibrin conversion at the injured organ; however, insufficient understanding of the stoichiometric coupling between active components of FHP may limit its coagulation performance. Here, we report a novel FHP (nFHP) through orthogonal optimization of fibrinogen, thrombin, and calcium chloride. Systematic screening identified fibrinogen concentration as the primary determinant of clotting time, with fibrinogen-to-thrombin and fibrinogen-to-calcium chloride ratios further impacting. nFHP, fabricated with the optimal formulation (17 mg/cm<sup>2</sup> fibrinogen, 40 IU/cm<sup>2</sup> thrombin, 115 μg/cm<sup>2</sup> calcium chloride), achieved rapid fibrin network formation and superior adhesive strength on the porcine aorta, surpassing commercial FHP (cFHP). In vivo evaluations across hepatic resection, cardiac stab wound, and arterial hemorrhage models demonstrated nFHP's universal efficacy, achieving the minimal blood loss compared to commercial products. Our work identifies stoichiometric proportion as a key factor in fibrin-based biomaterial rational design and provides a translatable solution for uncontrolled internal hemorrhage.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"258 ","pages":"Article 109584"},"PeriodicalIF":3.4,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977990","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 : 2026-01-08DOI: 10.1016/j.thromres.2026.109582
Joanna Natorska , Magdalena Kopytek , Aleksandra Gołąb , Anna Waśniowska , Małgorzata Konieczyńska , Anetta Undas , Michał Ząbczyk
Background
Thromboelastography (TEG) is used in various clinical settings to assess clot formation, strength, and lysis. It is unknown whether TEG measures correspond to plasma fibrin clot characteristics.
Methods
In 90 individuals free of cardiovascular disease (51 [56.7%] women, aged 49.3 ± 5.2 years, body-mass index [BMI], 26 [23.8–29.3] kg/m2) we assessed whole blood clot parameters (reaction [R] and clot formation [K] time, clot growth kinetics [angle], maximum amplitude [MA], and clot lysis [LY30]) using the TEG 6s analyzer (Haemonetics, Boston, US), plasma clot permeability (Ks), and clot lysis time (CLT) using three assays: (1) by Pieters (CLT-2018), (2) by Lisman (CLT), and (3) by Carter (Lys50).
Results
There were associations of Ks with K time (R = 0.29, p = 0.0053), angle (R = -0.31, p = 0.0033), and MA (R = −0.47, p < 0.0001), while CLT tended to correlate with LY30. In women compared to men Ks was 8.4% lower corresponding to 7% higher MA (both p < 0.001). In obese (n = 19, 21.1%) vs. non-obese individuals angle was 5% larger (p = 0.029) but BMI did not correlate with TEG measures. TEG parameters and fibrin clot properties were unaffected by smoking, hypertension or hyperlipidemia. More efficient fibrinolysis (LY30 > 2.6%) was detected in 15 (16.7%) individuals who had also shorter CLT-2018 and CLT (both p < 0.05). Hypofibrinolysis (CLT-2018 > 300 min; n = 8, 8.9%) was detected only using CLT with no differences in TEG indices or Lys50.
Conclusions
TEG and plasma fibrin clot properties are complementary methods for assessing hemostasis, however, fibrin clot properties better reflect the impact of clinical risk factors on fibrinogen modification.
{"title":"Comparative analysis of whole blood clot viscoelastic properties via thromboelastography and plasma fibrin clot characteristics","authors":"Joanna Natorska , Magdalena Kopytek , Aleksandra Gołąb , Anna Waśniowska , Małgorzata Konieczyńska , Anetta Undas , Michał Ząbczyk","doi":"10.1016/j.thromres.2026.109582","DOIUrl":"10.1016/j.thromres.2026.109582","url":null,"abstract":"<div><h3>Background</h3><div>Thromboelastography (TEG) is used in various clinical settings to assess clot formation, strength, and lysis. It is unknown whether TEG measures correspond to plasma fibrin clot characteristics.</div></div><div><h3>Methods</h3><div>In 90 individuals free of cardiovascular disease (51 [56.7%] women, aged 49.3 ± 5.2 years, body-mass index [BMI], 26 [23.8–29.3] kg/m<sup>2</sup>) we assessed whole blood clot parameters (reaction [R] and clot formation [K] time, clot growth kinetics [angle], maximum amplitude [MA], and clot lysis [LY30]) using the TEG 6s analyzer (Haemonetics, Boston, US), plasma clot permeability (Ks), and clot lysis time (CLT) using three assays: (1) by Pieters (CLT-2018), (2) by Lisman (CLT), and (3) by Carter (Lys50).</div></div><div><h3>Results</h3><div>There were associations of Ks with K time (<em>R</em> = 0.29, <em>p</em> = 0.0053), angle (R = -0.31, <em>p</em> = 0.0033), and MA (<em>R</em> = −0.47, <em>p</em> < 0.0001), while CLT tended to correlate with LY30. In women compared to men Ks was 8.4% lower corresponding to 7% higher MA (both <em>p</em> < 0.001). In obese (<em>n</em> = 19, 21.1%) vs. non-obese individuals angle was 5% larger (<em>p</em> = 0.029) but BMI did not correlate with TEG measures. TEG parameters and fibrin clot properties were unaffected by smoking, hypertension or hyperlipidemia. More efficient fibrinolysis (LY30 > 2.6%) was detected in 15 (16.7%) individuals who had also shorter CLT-2018 and CLT (both <em>p</em> < 0.05). Hypofibrinolysis (CLT-2018 > 300 min; <em>n</em> = 8, 8.9%) was detected only using CLT with no differences in TEG indices or Lys50.</div></div><div><h3>Conclusions</h3><div>TEG and plasma fibrin clot properties are complementary methods for assessing hemostasis, however, fibrin clot properties better reflect the impact of clinical risk factors on fibrinogen modification.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"258 ","pages":"Article 109582"},"PeriodicalIF":3.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979149","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 : 2026-01-07DOI: 10.1016/j.thromres.2025.109571
An Zhang , Guiyuan Li , Xiujian Wu
Venous thromboembolism is a major preventable complication among orthopedic inpatients, yet existing risk scores and correlation-driven models often miss complex physiological interactions and provide limited interpretability. We propose Causal-Aware Risk Embedding Network (CARE-Net), a causal representation learning framework for VTE prediction on structured clinical data. CARE-Net first infers a directed causal graph among laboratory, demographic, and therapeutic variables, then performs message passing strictly along causal directions to construct mechanism-aligned patient embeddings. A causal contrastive objective further aligns patients with similar causal signatures, enhancing robustness and suppressing spurious associations. Extensive comparisons with statistical, ensemble, deep tabular, transformer-based, and graph-based baselines show that CARE-Net delivers consistently superior discrimination and a more balanced sensitivity-specificity profile. Ablation and feature-importance analyses confirm that each causal component contributes meaningfully and that learned risk factors align with established clinical pathways. These findings suggest that embedding causal structure into representation learning offers a principled route to reliable VTE decision support in orthopedic care.
{"title":"CARE-Net: Causal-aware risk embedding for venous thromboembolism prediction in orthopedic inpatients","authors":"An Zhang , Guiyuan Li , Xiujian Wu","doi":"10.1016/j.thromres.2025.109571","DOIUrl":"10.1016/j.thromres.2025.109571","url":null,"abstract":"<div><div>Venous thromboembolism is a major preventable complication among orthopedic inpatients, yet existing risk scores and correlation-driven models often miss complex physiological interactions and provide limited interpretability. We propose Causal-Aware Risk Embedding Network (CARE-Net), a causal representation learning framework for VTE prediction on structured clinical data. CARE-Net first infers a directed causal graph among laboratory, demographic, and therapeutic variables, then performs message passing strictly along causal directions to construct mechanism-aligned patient embeddings. A causal contrastive objective further aligns patients with similar causal signatures, enhancing robustness and suppressing spurious associations. Extensive comparisons with statistical, ensemble, deep tabular, transformer-based, and graph-based baselines show that CARE-Net delivers consistently superior discrimination and a more balanced sensitivity-specificity profile. Ablation and feature-importance analyses confirm that each causal component contributes meaningfully and that learned risk factors align with established clinical pathways. These findings suggest that embedding causal structure into representation learning offers a principled route to reliable VTE decision support in orthopedic care.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"258 ","pages":"Article 109571"},"PeriodicalIF":3.4,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927657","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 : 2026-01-06DOI: 10.1016/j.thromres.2025.109580
Maria Chovi-Trull , Juan Eduardo Megías-Vericat , Tomás Palanques-Pastor , Ana Cid Haro , Manuel Rodriguez López , Antonio Palomero Massanet , Shally Marcellini Antonio , Saturnino Haya Guaita , Javier García Pellicer , Jose Luis Poveda Andrés , Santiago Bonanad Boix
Introduction
Extended half-life factor IX concentrates (FIX-EHL) have been shown to improve clinical outcomes and reduce treatment burden in patients with hemophilia B (HB).
Objectives
To analyze the differences in pharmacokinetic (PK) and clinical parameters one year before and after the PK-guided switch from standard half-life FIX (FIX-SHL) to FIX-EHL in patients with severe/moderate HB on prophylaxis.
Methods
A multicenter, comparative, observational, sequential, retrospective, and multidisciplinary study was conducted. PK parameters were calculated with WAPPS-Hemo®, and annualized total (ABR) and joint bleeding rates, the t1/2 ratio and area under the curve (AUC), FIX consumption, infusion frequency, and cost were recorded.
Results
A total of 21 patients (9 pediatric and 12 adult) with HB who switched from FIX-SHL to FIX-EHL were analyzed. All PK parameters improved significantly, with median improvement ratios for t1/2 and AUC of 4.1 (IQR: 3.4–4.8) and 4.2 (IQR: 2.6–5.0), respectively. Regarding clinical outcomes, the difference in ABR reached statistical significance and among the 6 patients with target joints, 5 (83.3 %) achieved resolution after switching. Infusion frequency and weekly dose were reduced by 50.0 % and 56.3 %, respectively, avoiding 52.1 (IQR: 26.1–67.8) injections and 130,357.3 (IQR: 5142.9–203,357.3) IU of FIX per patient per year. However, the switch resulted in an additional cost of € 28,254.9 (IQR: 4432.1- 44,060.8) per patient per year.
Conclusions
The PK-guided switch from FIX-SHL to FIX-EHL was associated with improvements in all PK parameters, and a significant clinical benefit was also demonstrated with the reduction of the bleeding rates. Following the switch, the weekly dose and administration frequency were reduced; however, this did not result in a cost reduction.
{"title":"Improvements in pharmacokinetics, bleeding control, and cost analysis after PK-guided transition to extended-half-life factor IX in hemophilia B: A multicentric study","authors":"Maria Chovi-Trull , Juan Eduardo Megías-Vericat , Tomás Palanques-Pastor , Ana Cid Haro , Manuel Rodriguez López , Antonio Palomero Massanet , Shally Marcellini Antonio , Saturnino Haya Guaita , Javier García Pellicer , Jose Luis Poveda Andrés , Santiago Bonanad Boix","doi":"10.1016/j.thromres.2025.109580","DOIUrl":"10.1016/j.thromres.2025.109580","url":null,"abstract":"<div><h3>Introduction</h3><div>Extended half-life factor IX concentrates (FIX-EHL) have been shown to improve clinical outcomes and reduce treatment burden in patients with hemophilia B (HB).</div></div><div><h3>Objectives</h3><div>To analyze the differences in pharmacokinetic (PK) and clinical parameters one year before and after the PK-guided switch from standard half-life FIX (FIX-SHL) to FIX-EHL in patients with severe/moderate HB on prophylaxis.</div></div><div><h3>Methods</h3><div>A multicenter, comparative, observational, sequential, retrospective, and multidisciplinary study was conducted. PK parameters were calculated with WAPPS-Hemo®, and annualized total (ABR) and joint bleeding rates, the t<sub>1/2</sub> ratio and area under the curve (AUC), FIX consumption, infusion frequency, and cost were recorded.</div></div><div><h3>Results</h3><div>A total of 21 patients (9 pediatric and 12 adult) with HB who switched from FIX-SHL to FIX-EHL were analyzed. All PK parameters improved significantly, with median improvement ratios for t<sub>1/2</sub> and AUC of 4.1 (IQR: 3.4–4.8) and 4.2 (IQR: 2.6–5.0), respectively. Regarding clinical outcomes, the difference in ABR reached statistical significance and among the 6 patients with target joints, 5 (83.3 %) achieved resolution after switching. Infusion frequency and weekly dose were reduced by 50.0 % and 56.3 %, respectively, avoiding 52.1 (IQR: 26.1–67.8) injections and 130,357.3 (IQR: 5142.9–203,357.3) IU of FIX per patient per year. However, the switch resulted in an additional cost of € 28,254.9 (IQR: 4432.1- 44,060.8) per patient per year.</div></div><div><h3>Conclusions</h3><div>The PK-guided switch from FIX-SHL to FIX-EHL was associated with improvements in all PK parameters, and a significant clinical benefit was also demonstrated with the reduction of the bleeding rates. Following the switch, the weekly dose and administration frequency were reduced; however, this did not result in a cost reduction.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"258 ","pages":"Article 109580"},"PeriodicalIF":3.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967192","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 : 2026-01-02DOI: 10.1016/j.thromres.2025.109581
Alexander Schmidt , Joschua Wiese , Fabian Tomschi , Barabara Boddenberg-Pätzold , Andreas Christian Strauss , Thomas Hilberg
Purpose
This systematic-review and meta-analysis investigated the effectiveness of radiosynoviorthesis (RSO) on clinical outcomes in male persons with haemophilia (PwH) and evaluated the quality of existing evidence.
Methods
Literature searches in PubMed and Web of Science identified 31 studies, with 17 included in the meta-analysis. Random-effects models were computed to analyse RSO-related changes in bleeding frequency, pain, synovial hypertrophy, and orthopaedic joint score. Due to insufficient data, Range of Motion (RoM) changes could not be meta-analytically calculated. Mean differences (MD) for bleeding frequency and standardized mean differences (SMD) for the remaining outcomes were computed.
Results
Results showed significant reductions in bleeding frequency at six months (MD = −5.93 [95 %-CI: −7.80, −4.06], p < 0.001, k = 10) and twelve months (MD = −7.83 [95 %-CI: −12.11, −3.55], p < 0.001, k = 6). Six months post treatment, pain (SMD = −1.31 [95 %-CI: −2.25, −0.38], p = 0.006, k = 5), synovial hypertrophy (SMD = −0.50 [95 %-CI: −0.65, −0.36], p < 0.001, k = 4), and orthopaedic joint score (SMD = −0.61 [95 %-CI: −0.92, −0.30], p < 0.001, k = 4) showed moderate to large improvements. Average RoM changes were minimal (2.6 % improvement). The overall complication rate was 12 per 1000 treated joints.
Conclusion
Despite promising results, the overall quality of evidence was moderate to low due to high methodological heterogeneity and lack of control groups. These findings suggest RSO is a safe and effective treatment for key clinical outcomes in PwH, but further well-designed controlled trials are needed to confirm these results.
目的：本系统综述和荟萃分析探讨了放射滑膜术（RSO）对男性血友病（PwH）患者临床结果的有效性，并评估了现有证据的质量。方法在PubMed和Web of Science中检索了31项研究，其中17项纳入了meta分析。计算随机效应模型来分析与rso相关的出血频率、疼痛、滑膜肥厚和骨科关节评分的变化。由于数据不足，活动度（RoM）的变化不能进行meta分析计算。计算出血频率的平均差异（MD）和其余结果的标准化平均差异（SMD）。结果6个月时（MD = - 5.93 [95% -CI: - 7.80, - 4.06], p < 0.001, k = 10）和12个月时（MD = - 7.83 [95% -CI: - 12.11, - 3.55], p < 0.001, k = 6）出血频率显著降低。治疗6个月后，疼痛（SMD = - 1.31 [95% -CI: - 2.25, - 0.38], p = 0.006, k = 5）、滑膜肥厚（SMD = - 0.50 [95% -CI: - 0.65, - 0.36], p < 0.001, k = 4）和矫形关节评分（SMD = - 0.61 [95% -CI: - 0.92, - 0.30], p < 0.001, k = 4）均有中度至重度改善。平均RoM变化最小（改善2.6%）。总并发症发生率为12 / 1000。结论尽管结果令人鼓舞，但由于方法学的高度异质性和缺乏对照组，证据的总体质量为中到低。这些发现表明，对于PwH的关键临床结果，RSO是一种安全有效的治疗方法，但需要进一步精心设计的对照试验来证实这些结果。
{"title":"Efficacy of radiosynoviorthesis on clinical outcomes in persons with haemophilia. A systematic review and meta-analysis","authors":"Alexander Schmidt , Joschua Wiese , Fabian Tomschi , Barabara Boddenberg-Pätzold , Andreas Christian Strauss , Thomas Hilberg","doi":"10.1016/j.thromres.2025.109581","DOIUrl":"10.1016/j.thromres.2025.109581","url":null,"abstract":"<div><h3>Purpose</h3><div>This systematic-review and meta-analysis investigated the effectiveness of radiosynoviorthesis (RSO) on clinical outcomes in male persons with haemophilia (PwH) and evaluated the quality of existing evidence.</div></div><div><h3>Methods</h3><div>Literature searches in PubMed and Web of Science identified 31 studies, with 17 included in the meta-analysis. Random-effects models were computed to analyse RSO-related changes in bleeding frequency, pain, synovial hypertrophy, and orthopaedic joint score. Due to insufficient data, Range of Motion (RoM) changes could not be meta-analytically calculated. Mean differences (MD) for bleeding frequency and standardized mean differences (SMD) for the remaining outcomes were computed.</div></div><div><h3>Results</h3><div>Results showed significant reductions in bleeding frequency at six months (MD = −5.93 [95 %-CI: −7.80, −4.06], <em>p</em> < 0.001, k = 10) and twelve months (MD = −7.83 [95 %-CI: −12.11, −3.55], p < 0.001, k = 6). Six months post treatment, pain (SMD = −1.31 [95 %-CI: −2.25, −0.38], <em>p</em> = 0.006, k = 5), synovial hypertrophy (SMD = −0.50 [95 %-CI: −0.65, −0.36], <em>p</em> < 0.001, k = 4), and orthopaedic joint score (SMD = −0.61 [95 %-CI: −0.92, −0.30], p < 0.001, k = 4) showed moderate to large improvements. Average RoM changes were minimal (2.6 % improvement). The overall complication rate was 12 per 1000 treated joints.</div></div><div><h3>Conclusion</h3><div>Despite promising results, the overall quality of evidence was moderate to low due to high methodological heterogeneity and lack of control groups. These findings suggest RSO is a safe and effective treatment for key clinical outcomes in PwH, but further well-designed controlled trials are needed to confirm these results.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"258 ","pages":"Article 109581"},"PeriodicalIF":3.4,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927718","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 : 2026-01-02DOI: 10.1016/j.thromres.2025.109573
For the DELPHI Serenity Group, Isabelle Mahé , Skerdi Haviari , Nassima Si Mohammed , Anette Arbjerg Højen , Carme Font , Stavros Konstantinides , Marieke J.H.A. Kruip , Luigi Maiorana , Sebastian Szmit , Denise Abbel , Laurent Bertoletti , Adrian Edwards , Michelle Edwards , Alessandra Gava , Jacobijn Gussekloo , Miriam J. Johnson , Rashmi Kumar , Johan Langendoen , Kate J. Lifford , Camille Couffignal
Introduction
To develop a European shared decision-support tool (SDST), a two-round Delphi process was used to achieve consensus on aspects relating to the antithrombotic therapy (ATT) deprescribing discussions and process in end-of-life cancer patients.
Methods
Conducted between September 2024 and March 2025, the Delphi survey was developed by a multidisciplinary 24-member steering committee (SC), including medical specialists in oncology, hematology, palliative care, primary care, geriatrics, and vascular medicine. The survey involved 188 experts from these specialties across eight European countries. Consensus was defined with pooled items as ≥70 % agreement with a final decision by the SC. Themes covered deprescribing timing, stakeholders, reassessment and clinical drivers of patients with ATT, SDST, and choice of outcomes for a randomized controlled trial (RCT) to evaluate the SDST.
Results
Round 1 reached consensus for seven pooled questions (37 %), especially the reassessment of ATT deprescribing. Considering these results, the SC reformulated round 2 to reduce ambiguity and move toward consensus. The SC made the final decision. Three medical specialties should be involved in ATT deprescribing: palliative care specialists, oncologists, and general practitioners after a triggering circumstance such as clinical triggers or at 3-month prognosis. For the SDST design, the findings confirmed that this tool would be meaningful to clinicians. Eleven predefined outcomes were selected for a future RCT.
Conclusion
These results succeeded in shaping the content of the future SDST and mapping its useability in palliative care clinical pathways across Europe, with the perspective to support informed decision-making, reduce complications, and improve quality of life in this population.
{"title":"Developing a decision support tool for the continuation or deprescribing of antithrombotic therapy in patients receiving end-of-life care: Results of a European Delphi study","authors":"For the DELPHI Serenity Group, Isabelle Mahé , Skerdi Haviari , Nassima Si Mohammed , Anette Arbjerg Højen , Carme Font , Stavros Konstantinides , Marieke J.H.A. Kruip , Luigi Maiorana , Sebastian Szmit , Denise Abbel , Laurent Bertoletti , Adrian Edwards , Michelle Edwards , Alessandra Gava , Jacobijn Gussekloo , Miriam J. Johnson , Rashmi Kumar , Johan Langendoen , Kate J. Lifford , Camille Couffignal","doi":"10.1016/j.thromres.2025.109573","DOIUrl":"10.1016/j.thromres.2025.109573","url":null,"abstract":"<div><h3>Introduction</h3><div>To develop a European shared decision-support tool (SDST), a two-round Delphi process was used to achieve consensus on aspects relating to the antithrombotic therapy (ATT) deprescribing discussions and process in end-of-life cancer patients.</div></div><div><h3>Methods</h3><div>Conducted between September 2024 and March 2025, the Delphi survey was developed by a multidisciplinary 24-member steering committee (SC), including medical specialists in oncology, hematology, palliative care, primary care, geriatrics, and vascular medicine. The survey involved 188 experts from these specialties across eight European countries. Consensus was defined with pooled items as ≥70 % agreement with a final decision by the SC. Themes covered deprescribing timing, stakeholders, reassessment and clinical drivers of patients with ATT, SDST, and choice of outcomes for a randomized controlled trial (RCT) to evaluate the SDST.</div></div><div><h3>Results</h3><div>Round 1 reached consensus for seven pooled questions (37 %), especially the reassessment of ATT deprescribing. Considering these results, the SC reformulated round 2 to reduce ambiguity and move toward consensus. The SC made the final decision. Three medical specialties should be involved in ATT deprescribing: palliative care specialists, oncologists, and general practitioners after a triggering circumstance such as clinical triggers or at 3-month prognosis. For the SDST design, the findings confirmed that this tool would be meaningful to clinicians. Eleven predefined outcomes were selected for a future RCT.</div></div><div><h3>Conclusion</h3><div>These results succeeded in shaping the content of the future SDST and mapping its useability in palliative care clinical pathways across Europe, with the perspective to support informed decision-making, reduce complications, and improve quality of life in this population.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"258 ","pages":"Article 109573"},"PeriodicalIF":3.4,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977994","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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