Pub Date : 2025-11-10DOI: 10.1016/j.thromres.2025.109534
Hem Regmi , Irene Li , Stephanie Prozora , Anish Sharda , Veronika Shabanova , E. Vincent S. Faustino , CRETE Trial and ATLAS Investigators
Background
Platelets release different substances when activated, such as during critical illness when children are inflamed. We explored the associations of catheter-associated deep venous thrombosis (CADVT), clinically relevant bleeding (CRB) and prophylactic enoxaparin with biomarkers of platelet activation and inflammation in critically ill children.
Methods
We analyzed platelet-poor plasma collected from critically ill children <18 years old with central venous catheter (CVC) enrolled in 2 multicenter studies conducted between 2017 and 2024. Blood was obtained on the day of, day after and 4 days after insertion of the CVC. Children were monitored daily for CRB and systematically surveilled for CADVT using ultrasonography. P-selectin, CD40L, platelet factor 4, RANTES, human thrombospondin 1, IL-1β, IL-2, IL-6, IL-8 and TNF-α were measured using immunosorbent assays.
Results
We studied plasma from 126 children (median: 9.6 years; interquartile range: 1.2, 15.3 years), of whom 24 received prophylactic enoxaparin. CADVT developed in 37.6 % and CRB in 31.0 % of children. Among children without prophylactic enoxaparin, CADVT was associated with high P-selectin and IL-6. A biomarker-augmented model with P-selectin and IL-6 seemed to perform better than a clinical model with age group, severity of illness and platelet count in identifying critically ill children with CADVT. CRB was associated with high platelet factor 4, while prophylactic enoxaparin was associated with high TNF-α.
Conclusions
Our findings suggest the role of platelet activation in CADVT in critically ill children. Once confirmed, these biomarkers may be used to identify critically ill children who would benefit from pharmacologic prophylaxis.
{"title":"Platelet-related biomarkers and catheter-associated thrombosis in critically ill children: An exploratory study","authors":"Hem Regmi , Irene Li , Stephanie Prozora , Anish Sharda , Veronika Shabanova , E. Vincent S. Faustino , CRETE Trial and ATLAS Investigators","doi":"10.1016/j.thromres.2025.109534","DOIUrl":"10.1016/j.thromres.2025.109534","url":null,"abstract":"<div><h3>Background</h3><div>Platelets release different substances when activated, such as during critical illness when children are inflamed. We explored the associations of catheter-associated deep venous thrombosis (CADVT), clinically relevant bleeding (CRB) and prophylactic enoxaparin with biomarkers of platelet activation and inflammation in critically ill children.</div></div><div><h3>Methods</h3><div>We analyzed platelet-poor plasma collected from critically ill children <18 years old with central venous catheter (CVC) enrolled in 2 multicenter studies conducted between 2017 and 2024. Blood was obtained on the day of, day after and 4 days after insertion of the CVC. Children were monitored daily for CRB and systematically surveilled for CADVT using ultrasonography. P-selectin, CD40L, platelet factor 4, RANTES, human thrombospondin 1, IL-1β, IL-2, IL-6, IL-8 and TNF-α were measured using immunosorbent assays.</div></div><div><h3>Results</h3><div>We studied plasma from 126 children (median: 9.6 years; interquartile range: 1.2, 15.3 years), of whom 24 received prophylactic enoxaparin. CADVT developed in 37.6 % and CRB in 31.0 % of children. Among children without prophylactic enoxaparin, CADVT was associated with high P-selectin and IL-6. A biomarker-augmented model with P-selectin and IL-6 seemed to perform better than a clinical model with age group, severity of illness and platelet count in identifying critically ill children with CADVT. CRB was associated with high platelet factor 4, while prophylactic enoxaparin was associated with high TNF-α.</div></div><div><h3>Conclusions</h3><div>Our findings suggest the role of platelet activation in CADVT in critically ill children. Once confirmed, these biomarkers may be used to identify critically ill children who would benefit from pharmacologic prophylaxis.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109534"},"PeriodicalIF":3.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145507026","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 : 2025-11-10DOI: 10.1016/j.thromres.2025.109537
Tian Gao , Ling Wang , Boheng Wang , Rui Yin , Li Qian , Aiqin Zhai , Vakkas Qureshi , Can Yang , Fei Han , Shuo Wang , Dan Wang , Xueping Xu , Xiujuan Wang , Kang Han , Ping Li , Xinjian Zhou , Xiaoman Ye , Runkai Shao , Lu Chen , Wei Wang , Yuan Mao
<div><h3>Background</h3><div>Pneumonia-related sepsis is frequently complicated by coagulation disorders, which significantly increase mortality risk. The current ISTH criteria demonstrate limited sensitivity in diagnosing pneumonia-specific coagulopathy, and the mechanisms underlying clinical phenotypic heterogeneity remain poorly understood. There is a growing need to identify novel biomarkers that can enhance the early detection and stratification of disseminated intravascular coagulation (DIC), particularly in its non-overt stages.</div></div><div><h3>Aims</h3><div>The study aimed to evaluate the prognostic value of antithrombin (AT) and activated protein C (aPC) testing for predicting clinical deterioration and early DIC progression in adults with severe pneumonia-related sepsis.</div></div><div><h3>Methods</h3><div>We conducted a prospective observational cohort study of 86 adults with severe pneumonia-related sepsis admitted to the Intensive Care Unit (ICU). All patients underwent testing of AT and aPC upon enrollment. The predictive value of this biomarker combination was evaluated for the development of overt DIC within 72 h and 28-day all-cause mortality using receiver operating characteristic (ROC) analysis.</div></div><div><h3>Results</h3><div>Among 86 adults with severe pneumonia-related sepsis (median age 65 years; 56.9 % male), 18 (20.9 %) progressed to overt DIC within 72 h, and the 28-day mortality rate was 26.7 % (23/86). Compared with survivors, non-survivors exhibited significantly lower antithrombin activity (median 65 % vs. 78 %; <em>P</em> = 0.005) and higher activated protein C levels (median 127 pg/mL vs. 93.9 pg/mL; <em>P</em> < 0.001). Notably, the presence of overt DIC was the strongest predictor of mortality (OR = 144, 95 % CI: 18.66–1111.07). Similarly, patients with overt DIC exhibited markedly elevated aPC (P < 0.001). Among non-survivors, aPC was positively correlated with the 24-hour vasoactive-inotropic score (VIS; <em>r</em> = 0.567, <em>P</em> = 0.005). ROC analysis revealed that for predicting mortality, both aPC (AUC = 0.804, 95 % CI: 0.709–0.900) and the combined AT/aPC model (AUC = 0.814, 95 % CI: 0.714–0.913) significantly outperformed AT alone (AUC = 0.736, 95 % CI: 0.595–0.878).For predicting overt DIC, aPC (AUC = 0.859, 95 % CI: 0.778–0.939) and the combined model (AUC = 0.850, 95 % CI: 0.764–0.935) both demonstrated high accuracy. Notably, only the combined model effectively identified non-overt DIC (AUC = 0.850, 95 % CI: 0.768–0.932), whereas AT (AUC = 0.723) and aPC (AUC = 0.742) alone showed suboptimal performance.</div></div><div><h3>Conclusion</h3><div>In conclusion, this preliminary study identifies a combined AT/aPC model as a promising early predictor of DIC progression and mortality in pneumonia-sepsis. If validated in larger, multicentre cohorts, this simple two-biomarker approach provides a potential biomarker foundation for future studies investigating personalised anticoagulation st
{"title":"Superiority of a combined antithrombin and activated protein C model for predicting coagulopathy and mortality in pneumonia-related sepsis: A prospective cohort study","authors":"Tian Gao , Ling Wang , Boheng Wang , Rui Yin , Li Qian , Aiqin Zhai , Vakkas Qureshi , Can Yang , Fei Han , Shuo Wang , Dan Wang , Xueping Xu , Xiujuan Wang , Kang Han , Ping Li , Xinjian Zhou , Xiaoman Ye , Runkai Shao , Lu Chen , Wei Wang , Yuan Mao","doi":"10.1016/j.thromres.2025.109537","DOIUrl":"10.1016/j.thromres.2025.109537","url":null,"abstract":"<div><h3>Background</h3><div>Pneumonia-related sepsis is frequently complicated by coagulation disorders, which significantly increase mortality risk. The current ISTH criteria demonstrate limited sensitivity in diagnosing pneumonia-specific coagulopathy, and the mechanisms underlying clinical phenotypic heterogeneity remain poorly understood. There is a growing need to identify novel biomarkers that can enhance the early detection and stratification of disseminated intravascular coagulation (DIC), particularly in its non-overt stages.</div></div><div><h3>Aims</h3><div>The study aimed to evaluate the prognostic value of antithrombin (AT) and activated protein C (aPC) testing for predicting clinical deterioration and early DIC progression in adults with severe pneumonia-related sepsis.</div></div><div><h3>Methods</h3><div>We conducted a prospective observational cohort study of 86 adults with severe pneumonia-related sepsis admitted to the Intensive Care Unit (ICU). All patients underwent testing of AT and aPC upon enrollment. The predictive value of this biomarker combination was evaluated for the development of overt DIC within 72 h and 28-day all-cause mortality using receiver operating characteristic (ROC) analysis.</div></div><div><h3>Results</h3><div>Among 86 adults with severe pneumonia-related sepsis (median age 65 years; 56.9 % male), 18 (20.9 %) progressed to overt DIC within 72 h, and the 28-day mortality rate was 26.7 % (23/86). Compared with survivors, non-survivors exhibited significantly lower antithrombin activity (median 65 % vs. 78 %; <em>P</em> = 0.005) and higher activated protein C levels (median 127 pg/mL vs. 93.9 pg/mL; <em>P</em> < 0.001). Notably, the presence of overt DIC was the strongest predictor of mortality (OR = 144, 95 % CI: 18.66–1111.07). Similarly, patients with overt DIC exhibited markedly elevated aPC (P < 0.001). Among non-survivors, aPC was positively correlated with the 24-hour vasoactive-inotropic score (VIS; <em>r</em> = 0.567, <em>P</em> = 0.005). ROC analysis revealed that for predicting mortality, both aPC (AUC = 0.804, 95 % CI: 0.709–0.900) and the combined AT/aPC model (AUC = 0.814, 95 % CI: 0.714–0.913) significantly outperformed AT alone (AUC = 0.736, 95 % CI: 0.595–0.878).For predicting overt DIC, aPC (AUC = 0.859, 95 % CI: 0.778–0.939) and the combined model (AUC = 0.850, 95 % CI: 0.764–0.935) both demonstrated high accuracy. Notably, only the combined model effectively identified non-overt DIC (AUC = 0.850, 95 % CI: 0.768–0.932), whereas AT (AUC = 0.723) and aPC (AUC = 0.742) alone showed suboptimal performance.</div></div><div><h3>Conclusion</h3><div>In conclusion, this preliminary study identifies a combined AT/aPC model as a promising early predictor of DIC progression and mortality in pneumonia-sepsis. If validated in larger, multicentre cohorts, this simple two-biomarker approach provides a potential biomarker foundation for future studies investigating personalised anticoagulation st","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109537"},"PeriodicalIF":3.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517332","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 : 2025-11-09DOI: 10.1016/j.thromres.2025.109533
S.F.B. van der Horst , G. Chu , J. Seelig , E.M. Trinks-Roerdink , L. Voorhout , T.A.C. de Vries , A.P. van Alem , R.J. Beukema , L.V.A. Boersma , M.A. Brouwer , H. ten Cate , L.M. Faber , J.R. de Groot , Y.L. Gu , F.R. den Hartog , J.S.S.G. de Jong , Y. de Jong , C.J.H.J. Kirchhof , F.S. Kleijwegt , F.A. Klok , M.V. Huisman
Background
Atrial fibrillation/flutter (AF/AFL) is associated with an increased stroke risk, for which oral anticoagulation (OAC) is often indicated. Bleeding risk assessment is crucial in these patients to mitigate bleeding complications, yet AF guidelines do not recommend the use of any bleeding risk score (e.g., HAS-BLED) due to concerns about predictive accuracy. The AF-adapted VTE-BLEED (AF-BLEED) score was developed to predict major bleeding (MB) post-OAC initiation.
Aims
Evaluate the incidence of clinically relevant bleeding, and externally validate the AF-BLEED score in new-onset AF/AFL patients.
Methods
Patients enrolled in the DUTCH-AF registry, who started OAC at diagnosis were studied. AF-BLEED categorized patients as low-risk (score ≤ 3) or high-risk (score > 3) for bleeding. Outcomes were first (i) MB and (ii) composite MB and clinically relevant non-major bleeding (CRNMB), with death and OAC discontinuation as competing events. Discrimination (cumulative AUC [AUCt]) was evaluated at 180 days and 2 years.
Results
4647 patients (AF-BLEED low-risk: 94.0 %) were included. Cumulative MB incidences for low- and high-risk patients were 0.58 % (95 %CI 0.34–0.82 %) and 1.65 % (0.04–3.26 %) at 180 days (p 0.04), and 1.82 % (1.39–2.26 %) and 5.07 % (2.26–7.87 %) at 2 years (p < 0.001), respectively. Cumulative CRNMB/MB incidences for low- and high-risk patients were 1.81 % (1.39–2.24 %) and 4.13 % (1.62–6.65 %) at 180 days (p 0.01), and 6.37 % (5.58–7.16 %) and 9.68 % (5.91–13.45 %) at 2 years (p 0.04), respectively. Discrimination was poor to moderate for both outcomes at both time windows, ranging between 0.51 and 0.62.
Conclusion
Although AF-BLEED was associated with subsequent risk of clinically relevant bleeding, its discriminative ability was poor, limiting the practical utility in its current form.
{"title":"Predicting clinically relevant bleeding in new-onset atrial fibrillation patients initiating oral anticoagulant therapy: External validation of the AF-BLEED score","authors":"S.F.B. van der Horst , G. Chu , J. Seelig , E.M. Trinks-Roerdink , L. Voorhout , T.A.C. de Vries , A.P. van Alem , R.J. Beukema , L.V.A. Boersma , M.A. Brouwer , H. ten Cate , L.M. Faber , J.R. de Groot , Y.L. Gu , F.R. den Hartog , J.S.S.G. de Jong , Y. de Jong , C.J.H.J. Kirchhof , F.S. Kleijwegt , F.A. Klok , M.V. Huisman","doi":"10.1016/j.thromres.2025.109533","DOIUrl":"10.1016/j.thromres.2025.109533","url":null,"abstract":"<div><h3>Background</h3><div>Atrial fibrillation/flutter (AF/AFL) is associated with an increased stroke risk, for which oral anticoagulation (OAC) is often indicated. Bleeding risk assessment is crucial in these patients to mitigate bleeding complications, yet AF guidelines do not recommend the use of any bleeding risk score (e.g., HAS-BLED) due to concerns about predictive accuracy. The AF-adapted VTE-BLEED (AF-BLEED) score was developed to predict major bleeding (MB) post-OAC initiation.</div></div><div><h3>Aims</h3><div>Evaluate the incidence of clinically relevant bleeding, and externally validate the AF-BLEED score in new-onset AF/AFL patients.</div></div><div><h3>Methods</h3><div>Patients enrolled in the DUTCH-AF registry, who started OAC at diagnosis were studied. AF-BLEED categorized patients as low-risk (score ≤ 3) or high-risk (score > 3) for bleeding. Outcomes were first (i) MB and (ii) composite MB and clinically relevant non-major bleeding (CRNMB), with death and OAC discontinuation as competing events. Discrimination (cumulative AUC [AUCt]) was evaluated at 180 days and 2 years.</div></div><div><h3>Results</h3><div>4647 patients (AF-BLEED low-risk: 94.0 %) were included. Cumulative MB incidences for low- and high-risk patients were 0.58 % (95 %CI 0.34–0.82 %) and 1.65 % (0.04–3.26 %) at 180 days (<em>p</em> 0.04), and 1.82 % (1.39–2.26 %) and 5.07 % (2.26–7.87 %) at 2 years (p < 0.001), respectively. Cumulative CRNMB/MB incidences for low- and high-risk patients were 1.81 % (1.39–2.24 %) and 4.13 % (1.62–6.65 %) at 180 days (<em>p</em> 0.01), and 6.37 % (5.58–7.16 %) and 9.68 % (5.91–13.45 %) at 2 years (<em>p</em> 0.04), respectively. Discrimination was poor to moderate for both outcomes at both time windows, ranging between 0.51 and 0.62.</div></div><div><h3>Conclusion</h3><div>Although AF-BLEED was associated with subsequent risk of clinically relevant bleeding, its discriminative ability was poor, limiting the practical utility in its current form.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109533"},"PeriodicalIF":3.4,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517379","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 : 2025-11-09DOI: 10.1016/j.thromres.2025.109535
R.J.S. Anijs , Y.N. Nguyen , M. Yanovska , R. van den Akker , E.H. Laghmani , B. Ünlü , S.C. Cannegieter , J.T. Buijs , H.H. Versteeg , A.M.R. Rondon
Background
Colorectal cancer (CRC) patients are at increased risk of developing venous thromboembolism (VTE), leading to high morbidity and mortality. The exact mechanism remains unknown, which complicates risk prediction and treatment. Previously, using RNA-sequencing, Regenerating islet derived Family Member 4 (REG4) was identified to be upregulated in tumor cells from CRC patients with VTE compared to tumor cells from CRC patients without VTE.
Objective
Here we aim to functionally validate the role of REG4 in cancer-associated thrombosis (CAT) using different in vitro tests of thrombosis and hemostasis.
Methods
Recombinant purified protein (rREG4), as well as REG4 overexpressing human colorectal cell lines were used to characterize the possible role of REG4. Prothrombin time (pT), activated partial thromboplastin time (aPTT) in normal pooled plasma (NPP) and whole blood and thrombin generation in NPP were determined in the presence of rREG4. In addition, the effect of rREG4 and RKO-REG4 expressing cells on plasma clot turbidity after exposure to human umbilical vein endothelial cell (HUVEC) was assessed by a turbidimetric assay, qPCR and Electric Cell-substrate Impedance Sensing (ECIS). In an organ-on-a-chip-model for cancer-associated hypercoagulability, RKO cells were co-cultured with vessel-forming HUVECs, after which thrombin generation was assessed.
Results
rREG4 did not alter pT and aPTT clotting times nor the thrombin generation potential in NPP and whole blood. Conditioned medium of RKO-REG4 secreting cells did not alter the thrombin generation potential, compared to the negative control (mock transfected RKO cells). In addition, no effect was observed on in vitro turbidimetric clot formation or on ECIS after endothelial cell stimulation. In line with this, using a cancer-associated hypercoagulability-on-a-chip model, RKO-REG4 cells did not further influence endothelial barrier integrity, nor thrombin generation potential, compared to control RKO cells.
Conclusions
Extensive in vitro and microfluidic methods showed no effect of REG4 on coagulation parameters in CRC. Further research is needed into the mechanism behind CAT, as its understanding will help in better risk prediction and treatment.
{"title":"Regenerating islet derived Family Member 4 (REG4) does not influence parameters of hemostasis in colorectal cancer","authors":"R.J.S. Anijs , Y.N. Nguyen , M. Yanovska , R. van den Akker , E.H. Laghmani , B. Ünlü , S.C. Cannegieter , J.T. Buijs , H.H. Versteeg , A.M.R. Rondon","doi":"10.1016/j.thromres.2025.109535","DOIUrl":"10.1016/j.thromres.2025.109535","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) patients are at increased risk of developing venous thromboembolism (VTE), leading to high morbidity and mortality. The exact mechanism remains unknown, which complicates risk prediction and treatment. Previously, using RNA-sequencing, <em>Regenerating islet derived Family Member 4 (REG4)</em> was identified to be upregulated in tumor cells from CRC patients with VTE compared to tumor cells from CRC patients without VTE.</div></div><div><h3>Objective</h3><div>Here we aim to functionally validate the role of REG4 in cancer-associated thrombosis (CAT) using different <em>in vitro</em> tests of thrombosis and hemostasis.</div></div><div><h3>Methods</h3><div>Recombinant purified protein (rREG4), as well as REG4 overexpressing human colorectal cell lines were used to characterize the possible role of REG4. Prothrombin time (pT), activated partial thromboplastin time (aPTT) in normal pooled plasma (NPP) and whole blood and thrombin generation in NPP were determined in the presence of rREG4. In addition, the effect of rREG4 and RKO-REG4 expressing cells on plasma clot turbidity after exposure to human umbilical vein endothelial cell (HUVEC) was assessed by a turbidimetric assay, qPCR and Electric Cell-substrate Impedance Sensing (ECIS). In an organ-on-a-chip-model for cancer-associated hypercoagulability, RKO cells were co-cultured with vessel-forming HUVECs, after which thrombin generation was assessed.</div></div><div><h3>Results</h3><div>rREG4 did not alter pT and aPTT clotting times nor the thrombin generation potential in NPP and whole blood. Conditioned medium of RKO-REG4 secreting cells did not alter the thrombin generation potential, compared to the negative control (mock transfected RKO cells). In addition, no effect was observed on <em>in vitro</em> turbidimetric clot formation or on ECIS after endothelial cell stimulation. In line with this, using a cancer-associated hypercoagulability-on-a-chip model, RKO-REG4 cells did not further influence endothelial barrier integrity, nor thrombin generation potential, compared to control RKO cells.</div></div><div><h3>Conclusions</h3><div>Extensive <em>in vitro</em> and microfluidic methods showed no effect of REG4 on coagulation parameters in CRC. Further research is needed into the mechanism behind CAT, as its understanding will help in better risk prediction and treatment.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109535"},"PeriodicalIF":3.4,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513977","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}
Trauma-induced coagulopathy (TIC) significantly impacts trauma prognosis, necessitating early intervention. The Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) criteria are one of the indicators for TIC, and modified criteria, JAAM-2 DIC criteria, have recently been proposed. We aimed to investigate the predictive ability of the JAAM-2 DIC criteria and its components for critical bleeding during the acute trauma phase.
Methods
This retrospective observational study used a nationwide Japanese database, including 2.7 million patients admitted between 2014 and 2023. We included adult inpatients transported by emergency medical services due to trauma. The JAAM-2 DIC scores on admission were calculated based on platelet count, prothrombin time-international normalized ratio (PT-INR), and fibrinogen/fibrin degradation products (FDP). The primary endpoint was critical bleeding, defined as a composite of death within 24-h or massive transfusion (receiving ≥10 units of red blood cells transfusion within 2 days). We investigated the relationship between the JAAM-2 DIC score, its components, and outcomes using the area under the receiver operating characteristic curve (AUC).
Results
Among the 10,834 patients with trauma, 1.7 % had critical bleeding. The JAAM-2 DIC score had an AUC of 0.802, with PT-INR showing the highest AUC of 0.836 among its components. The FDP score distribution was more irregular than the others, weakening the JAAM-2 DIC score's association with prognosis.
Conclusion
The JAAM-2 DIC criteria can predict critical bleeding in trauma. Identifying and revising FDP scoring issues in JAAM-2 DIC criteria for trauma improved AUC for predicting critical bleeding.
{"title":"Validation of the Japanese Association for Acute Medicine-2 disseminated intravascular coagulation criteria to predict critical bleeding in patients with trauma: A nationwide cohort study in Japan","authors":"Masaki Takahashi , Takeshi Wada , Takumi Tsuchida , Hirotaka Mori , Yutaka Umemura , Kazuma Yamakawa , Kohji Okamoto","doi":"10.1016/j.thromres.2025.109532","DOIUrl":"10.1016/j.thromres.2025.109532","url":null,"abstract":"<div><h3>Background</h3><div>Trauma-induced coagulopathy (TIC) significantly impacts trauma prognosis, necessitating early intervention. The Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) criteria are one of the indicators for TIC, and modified criteria, JAAM-2 DIC criteria, have recently been proposed. We aimed to investigate the predictive ability of the JAAM-2 DIC criteria and its components for critical bleeding during the acute trauma phase.</div></div><div><h3>Methods</h3><div>This retrospective observational study used a nationwide Japanese database, including 2.7 million patients admitted between 2014 and 2023. We included adult inpatients transported by emergency medical services due to trauma. The JAAM-2 DIC scores on admission were calculated based on platelet count, prothrombin time-international normalized ratio (PT-INR), and fibrinogen/fibrin degradation products (FDP). The primary endpoint was critical bleeding, defined as a composite of death within 24-h or massive transfusion (receiving ≥10 units of red blood cells transfusion within 2 days). We investigated the relationship between the JAAM-2 DIC score, its components, and outcomes using the area under the receiver operating characteristic curve (AUC).</div></div><div><h3>Results</h3><div>Among the 10,834 patients with trauma, 1.7 % had critical bleeding. The JAAM-2 DIC score had an AUC of 0.802, with PT-INR showing the highest AUC of 0.836 among its components. The FDP score distribution was more irregular than the others, weakening the JAAM-2 DIC score's association with prognosis.</div></div><div><h3>Conclusion</h3><div>The JAAM-2 DIC criteria can predict critical bleeding in trauma. Identifying and revising FDP scoring issues in JAAM-2 DIC criteria for trauma improved AUC for predicting critical bleeding.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109532"},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514031","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 : 2025-11-07DOI: 10.1016/j.thromres.2025.109531
Sarah E. Tashbook , Tomasz W. Kaminski , Claudette M. St. Croix , Simon C. Watkins , Prithu Sundd , Tomasz Brzoska
In situ pulmonary arterial thrombosis (iPAT), occurring without concurrent deep vein thrombosis, is a life-threatening complication associated with various pathological conditions. The etiological mechanisms underlying iPAT remain poorly understood. Several studies suggest that circulating tissue factor (cTF) may contribute to the development of thrombotic complications; however, there is no direct in vivo evidence supporting the role of cTF in the pathogenesis of iPAT. Furthermore, although in vitro studies suggest that platelet anionic phospholipids enable cTF-initiated coagulation, how platelets contribute to cTF-dependent iPAT in vivo remains unknown. In the current study, we used quantitative fluorescence intravital lung microscopy to investigate the development of cTF-induced iPAT in live mice following intravascular administration of thromboplastin. To dissect the interplay between coagulation and platelet procoagulant activity, we assessed the effects of coagulation and platelet inhibition on iPAT development in vivo. Additionally, we conducted an in vitro clotting time assay using mouse plasma samples. Thromboplastin triggered iPAT in mice in a dose-dependent manner. IPAT involved the formation of platelet-rich thrombi at the bottle-neck junctions of pulmonary arterioles and capillaries, which was prevented by heparin. Notably, pretreatment of mice with annexin A5 or eptifibatide also completely abrogated thromboplastin-induced iPAT. These intravital microscopy findings were further corroborated by the in vitro clotting time assay. Our study provides in vivo evidence that cTF contributes to the development of iPAT. We demonstrate that the prothrombotic effect of cTF is dependent on platelet-αIIbβ3 signaling, which enhances platelet procoagulant activity, leading to accelerated coagulation and development of iPAT.
{"title":"αIIbβ3-dependent platelet procoagulant activity promotes pulmonary arterial thrombosis triggered by circulating tissue factor","authors":"Sarah E. Tashbook , Tomasz W. Kaminski , Claudette M. St. Croix , Simon C. Watkins , Prithu Sundd , Tomasz Brzoska","doi":"10.1016/j.thromres.2025.109531","DOIUrl":"10.1016/j.thromres.2025.109531","url":null,"abstract":"<div><div><em>In situ</em> pulmonary arterial thrombosis (iPAT), occurring without concurrent deep vein thrombosis, is a life-threatening complication associated with various pathological conditions. The etiological mechanisms underlying iPAT remain poorly understood. Several studies suggest that circulating tissue factor (cTF) may contribute to the development of thrombotic complications; however, there is no direct <em>in vivo</em> evidence supporting the role of cTF in the pathogenesis of iPAT. Furthermore, although <em>in vitro</em> studies suggest that platelet anionic phospholipids enable cTF-initiated coagulation, how platelets contribute to cTF-dependent iPAT <em>in vivo</em> remains unknown. In the current study, we used quantitative fluorescence intravital lung microscopy to investigate the development of cTF-induced iPAT in live mice following intravascular administration of thromboplastin. To dissect the interplay between coagulation and platelet procoagulant activity, we assessed the effects of coagulation and platelet inhibition on iPAT development <em>in vivo</em>. Additionally, we conducted an <em>in vitro</em> clotting time assay using mouse plasma samples. Thromboplastin triggered iPAT in mice in a dose-dependent manner. IPAT involved the formation of platelet-rich thrombi at the bottle-neck junctions of pulmonary arterioles and capillaries, which was prevented by heparin. Notably, pretreatment of mice with annexin A5 or eptifibatide also completely abrogated thromboplastin-induced iPAT. These intravital microscopy findings were further corroborated by the <em>in vitro</em> clotting time assay. Our study provides <em>in vivo</em> evidence that cTF contributes to the development of iPAT. We demonstrate that the prothrombotic effect of cTF is dependent on platelet-αIIbβ3 signaling, which enhances platelet procoagulant activity, leading to accelerated coagulation and development of iPAT.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109531"},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496865","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 : 2025-11-07DOI: 10.1016/j.thromres.2025.109530
Massimo Nunes , Arneaux Kruger , Burtram Fielding , Douglas B. Kell , Etheresia Pretorius
Coagulation, although primarily regulated by platelets, endothelial cells, and clotting factors, can also be influenced by molecules that are not traditionally seen as related to coagulation, including cytokines, hormones, metabolites, reactive oxygen species, acute phase reactants, and more. Here, we derive pseudoserum or clotting factor-depleted fractions from control, type II diabetes mellitus, and Long COVID platelet-poor plasma (PPP) samples, and expose them to purified, exogenous fibrinogen obtained from healthy donors. Thrombin-induced fibrin networks were then formed and visualized using light and scanning electron microscopy. The results demonstrate that pseudoserum can greatly influence the organization, density, and ultrastructure of fibrin networks formed from purified fibrinogen, emphasizing the role of non-clotting factors in fibrin formation. Fibrin networks formed from purified fibrinogen exposed to control pseudoserum appear homogeneous, exhibiting organised architecture with few regions of unusual density or aggregates, whereas the networks formed using patient pseudoserum show disorganisation, regions of density, fibre-like strands, and anomalous aggregates. These abnormalities are also observed in patient PPP samples, suggesting that fibrin network characteristics in PPP samples are also significantly influenced by non-clotting factors and are somewhat independent of endogenous fibrinogen. Furthermore, fibrinolysis was significantly reduced in the patient groups, demonstrating the ability of pseudoserum to influence the susceptibility of fibrin networks to plasmin-induced degradation. The ability of pseudoserum to drive these changes, despite the essential absence of endogenous fibrinogen and other classical clotting factors, suggests that soluble molecules retained in pseudoserum can directly modify fibrinogen's structural conformation and functionality, influence thrombin-mediated fibrin formation and polymerization, and/or impact Factor XIII's crosslinking capabilities. This study provides a systems-level perspective on the influence of pseudoserum on fibrin networks and highlights the potential of serum and other clotting factor–depleted fractions to yield deeper mechanistic and diagnostic insights into coagulation.
{"title":"The effects of pseudoserum on thrombin-induced fibrin networks: Potential for clinical insight into coagulation independent of traditional parameters","authors":"Massimo Nunes , Arneaux Kruger , Burtram Fielding , Douglas B. Kell , Etheresia Pretorius","doi":"10.1016/j.thromres.2025.109530","DOIUrl":"10.1016/j.thromres.2025.109530","url":null,"abstract":"<div><div>Coagulation, although primarily regulated by platelets, endothelial cells, and clotting factors, can also be influenced by molecules that are not traditionally seen as related to coagulation, including cytokines, hormones, metabolites, reactive oxygen species, acute phase reactants, and more. Here, we derive pseudoserum or clotting factor-depleted fractions from control, type II diabetes mellitus, and Long COVID platelet-poor plasma (PPP) samples, and expose them to purified, exogenous fibrinogen obtained from healthy donors. Thrombin-induced fibrin networks were then formed and visualized using light and scanning electron microscopy. The results demonstrate that pseudoserum can greatly influence the organization, density, and ultrastructure of fibrin networks formed from purified fibrinogen, emphasizing the role of non-clotting factors in fibrin formation. Fibrin networks formed from purified fibrinogen exposed to control pseudoserum appear homogeneous, exhibiting organised architecture with few regions of unusual density or aggregates, whereas the networks formed using patient pseudoserum show disorganisation, regions of density, fibre-like strands, and anomalous aggregates. These abnormalities are also observed in patient PPP samples, suggesting that fibrin network characteristics in PPP samples are also significantly influenced by non-clotting factors and are somewhat independent of endogenous fibrinogen. Furthermore, fibrinolysis was significantly reduced in the patient groups, demonstrating the ability of pseudoserum to influence the susceptibility of fibrin networks to plasmin-induced degradation. The ability of pseudoserum to drive these changes, despite the essential absence of endogenous fibrinogen and other classical clotting factors, suggests that soluble molecules retained in pseudoserum can directly modify fibrinogen's structural conformation and functionality, influence thrombin-mediated fibrin formation and polymerization, and/or impact Factor XIII's crosslinking capabilities. This study provides a systems-level perspective on the influence of pseudoserum on fibrin networks and highlights the potential of serum and other clotting factor–depleted fractions to yield deeper mechanistic and diagnostic insights into coagulation.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109530"},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514016","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 : 2025-11-06DOI: 10.1016/j.thromres.2025.109529
Amir Mahmoud , Kristen M. Sanfilippo , Brian F. Gage , Suhong Luo , Amber Afzal
{"title":"Association of anticoagulant therapy with bleeding in patients with chronic liver disease: A case-cross over study using the National Veterans Health Administration database","authors":"Amir Mahmoud , Kristen M. Sanfilippo , Brian F. Gage , Suhong Luo , Amber Afzal","doi":"10.1016/j.thromres.2025.109529","DOIUrl":"10.1016/j.thromres.2025.109529","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109529"},"PeriodicalIF":3.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496789","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 : 2025-11-03DOI: 10.1016/j.thromres.2025.109525
Claudia Iglesias-Perez , Paula Jimenez-Fonseca , Javier López Robles , Silvia García Adrián , Isaura Fernández Pérez , Purificación Martínez del Prado , Jaime Rubio Pérez , Eva Martínez de Castro , Carmen Díaz Pedroche , Marta García de Herreros , Marta Carmona Campos , Ana Belén Rupérez Blanco , Mercedes Salgado Fernández , Teresa Quintanar Verdúguez , David Marrupe González , Marta Covela Rúa , Jose Antonio Santiago Crespo , María Nieva Muñoz , Andrés Muñoz , Alberto Carmona-Bayonas
Background
Cancer-associated venous thromboembolism (VTE) is a major adverse prognostic factor with heterogeneous outcomes across tumor types. We aimed to describe the characteristics of lung cancer patients with VTE, compare outcomes across malignancies, and assess their association with complications, progression, and survival.
Methods
We analyzed TESEO-SEOM, a prospective multicenter registry including patients with active cancer and VTE. Patients were stratified by tumor site, with lung as reference. Outcomes included recurrent VTE, bleeding, and survival. Analyses were stratified by tumor type and VTE presentation (clinically suspected, symptomatic/asymptomatic incidental). Complications were estimated using competing-risk methods.
Results
Among 3855 patients, the most frequent cancers were gastrointestinal (39.4 %), lung (22.2 %), and breast (10.4 %). Pulmonary embolism predominated (55 %), especially in lung cancer (69.8 %). Overall, 48.9 % of events were clinically suspected and 50.9 % incidental; suspected were more common in lung cancer (53.9 %), whereas incidental diagnoses predominated in gastrointestinal tumors (58.8 %).
Complications occurred in 17.6 % (10.2 % bleeding, 7.4 % recurrent VTE). Recurrence was highest in gastrointestinal cancers (11.4 %, Gray's p = 0.022), while bleeding did not differ (p = 0.213). VTE-related mortality was low (1 %), while mixed-cause mortality was highest in lung cancer (17.2 %). Median PFS and OS were shortest in lung cancer (4.5 and 7.7 months, p < 0.0001). Incidental asymptomatic events conferred longer survival, particularly in lung cancer (OS 11.5 vs. 7.3 months for symptomatic incidental and 5.6 for suspected, p < 0.001).
Conclusion
VTE in lung cancer is associated with more severe presentation, higher mixed-cause mortality, and worse survival than in other tumors. Incidental asymptomatic VTE predicts better outcomes, supporting risk stratification by tumor type and presentation.
癌症相关静脉血栓栓塞（VTE）是一种主要的不良预后因素，不同肿瘤类型的预后不尽相同。我们的目的是描述肺癌静脉血栓栓塞患者的特征，比较不同恶性肿瘤的预后，并评估其与并发症、进展和生存的关系。方法我们分析了TESEO-SEOM，一项前瞻性多中心登记，包括活动性癌症和静脉血栓栓塞患者。按肿瘤部位分层，以肺为参照。结果包括静脉血栓栓塞复发、出血和生存。根据肿瘤类型和静脉血栓栓塞表现（临床怀疑、有症状/无症状偶发）对分析进行分层。采用竞争风险法估计并发症。结果3855例患者中，最常见的肿瘤为胃肠道（39.4%）、肺癌（22.2%）和乳腺癌（10.4%）。肺栓塞占多数（55%），尤其是肺癌（69.8%）。总体而言，48.9%的事件为临床怀疑，50.9%为偶然事件；疑似多见于肺癌（53.9%），而偶然诊断主要见于胃肠道肿瘤（58.8%）。并发症发生率为17.6%（10.2%出血，7.4%静脉血栓栓塞复发）。胃肠道肿瘤复发率最高（11.4%,Gray’s p = 0.022），而出血无差异（p = 0.213）。静脉血栓栓塞相关死亡率较低（1%），而肺癌的混合原因死亡率最高（17.2%）。肺癌患者的中位PFS和OS最短（4.5个月和7.7个月，p < 0.0001）。偶发无症状事件可延长生存期，尤其是肺癌患者（偶发症状患者生存期11.5个月，疑似患者生存期7.3个月，p < 0.001）。结论与其他肿瘤相比，vte在肺癌中的表现更严重，混合原因死亡率更高，生存期更差。偶发无症状静脉血栓栓塞预测更好的预后，支持肿瘤类型和表现的风险分层。
{"title":"Venous thrombosis in lung cancer compared with other tumors: results from the TESEO-SEOM registry","authors":"Claudia Iglesias-Perez , Paula Jimenez-Fonseca , Javier López Robles , Silvia García Adrián , Isaura Fernández Pérez , Purificación Martínez del Prado , Jaime Rubio Pérez , Eva Martínez de Castro , Carmen Díaz Pedroche , Marta García de Herreros , Marta Carmona Campos , Ana Belén Rupérez Blanco , Mercedes Salgado Fernández , Teresa Quintanar Verdúguez , David Marrupe González , Marta Covela Rúa , Jose Antonio Santiago Crespo , María Nieva Muñoz , Andrés Muñoz , Alberto Carmona-Bayonas","doi":"10.1016/j.thromres.2025.109525","DOIUrl":"10.1016/j.thromres.2025.109525","url":null,"abstract":"<div><h3>Background</h3><div>Cancer-associated venous thromboembolism (VTE) is a major adverse prognostic factor with heterogeneous outcomes across tumor types. We aimed to describe the characteristics of lung cancer patients with VTE, compare outcomes across malignancies, and assess their association with complications, progression, and survival.</div></div><div><h3>Methods</h3><div>We analyzed TESEO-SEOM, a prospective multicenter registry including patients with active cancer and VTE. Patients were stratified by tumor site, with lung as reference. Outcomes included recurrent VTE, bleeding, and survival. Analyses were stratified by tumor type and VTE presentation (clinically suspected, symptomatic/asymptomatic incidental). Complications were estimated using competing-risk methods.</div></div><div><h3>Results</h3><div>Among 3855 patients, the most frequent cancers were gastrointestinal (39.4 %), lung (22.2 %), and breast (10.4 %). Pulmonary embolism predominated (55 %), especially in lung cancer (69.8 %). Overall, 48.9 % of events were clinically suspected and 50.9 % incidental; suspected were more common in lung cancer (53.9 %), whereas incidental diagnoses predominated in gastrointestinal tumors (58.8 %).</div><div>Complications occurred in 17.6 % (10.2 % bleeding, 7.4 % recurrent VTE). Recurrence was highest in gastrointestinal cancers (11.4 %, Gray's <em>p</em> = 0.022), while bleeding did not differ (<em>p</em> = 0.213). VTE-related mortality was low (1 %), while mixed-cause mortality was highest in lung cancer (17.2 %). Median PFS and OS were shortest in lung cancer (4.5 and 7.7 months, <em>p</em> < 0.0001). Incidental asymptomatic events conferred longer survival, particularly in lung cancer (OS 11.5 vs. 7.3 months for symptomatic incidental and 5.6 for suspected, <em>p</em> < 0.001).</div></div><div><h3>Conclusion</h3><div>VTE in lung cancer is associated with more severe presentation, higher mixed-cause mortality, and worse survival than in other tumors. Incidental asymptomatic VTE predicts better outcomes, supporting risk stratification by tumor type and presentation.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109525"},"PeriodicalIF":3.4,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517380","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 : 2025-11-03DOI: 10.1016/j.thromres.2025.109527
Yingying Li , Jiachen Liu , Lili Luo , Lijuan Zhou , Zhong Wu , Wei Sang , Huiwen Jiang , Jingming Wang , Xindi Wang , Peiru Li , Zhaozhao Chen , Jinhui Shu , Wenjing Luo , Yu Hu , Yuhua Li , Heng Mei
Background
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). While CAR-T-associated coagulopathy (CARAC) remains a critical complication, significantly increasing the risk of hemorrhage and disseminated intravascular coagulation (DIC).
Aims
To develop an effective CARAC risk stratification and outcome prediction model.
Methods
This multicenter retrospective study enrolled r/r B-ALL patients who received CD19 CAR-T therapy between January 2016 and July 2025. Machine learning, logistic regression and cutoff values were utilized to select key variables and develop predictive models. Model performance and clinical applicability were evaluated by receiver operating characteristic, calibration, and clinical decision curves. Survival analyses evaluated the impact of CARAC severity on overall survival (OS) and progression-free survival (PFS) and to validate the prognostic value of the prediction model.
Results
Bone marrow (BM) blasts and the modified endothelial activation and stress index (mEASIX) were independent predictors for CARAC. Patients with mEASIX<4.0 were identified as low-risk CARAC. For patients with mEASIX≥4.0, CARAC was stratified by BM blast percentage (blast%). Blast% between 10 % and 44 % indicated high-risk CARAC-nonDIC, and a blast% ≥ 44 % indicated high-risk CARAC-DIC. Moreover, compared to non-CARAC patients, CARAC patients had inferior OS (hazard ratio [HR]: 2.62, p = 0.002) and PFS (HR: 2.11, p = 0.002). The stratified prediction model revealed progressively worse OS and PFS from low-risk CARAC patients to high-risk CARAC-nonDIC, with high-risk CARAC-DIC patients demonstrating the most unfavorable outcomes.
Conclusions
An effective CARAC risk prediction and stratification model was established. High-risk CARAC patients, particularly CARAC-DIC, were associated with significantly worse outcomes.
{"title":"Bone marrow blasts- and modified EASIX-guided risk stratification for coagulopathy and outcomes after CAR-T therapy in relapsed/refractory B-ALL","authors":"Yingying Li , Jiachen Liu , Lili Luo , Lijuan Zhou , Zhong Wu , Wei Sang , Huiwen Jiang , Jingming Wang , Xindi Wang , Peiru Li , Zhaozhao Chen , Jinhui Shu , Wenjing Luo , Yu Hu , Yuhua Li , Heng Mei","doi":"10.1016/j.thromres.2025.109527","DOIUrl":"10.1016/j.thromres.2025.109527","url":null,"abstract":"<div><h3>Background</h3><div>Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). While CAR-T-associated coagulopathy (CARAC) remains a critical complication, significantly increasing the risk of hemorrhage and disseminated intravascular coagulation (DIC).</div></div><div><h3>Aims</h3><div>To develop an effective CARAC risk stratification and outcome prediction model.</div></div><div><h3>Methods</h3><div>This multicenter retrospective study enrolled r/r B-ALL patients who received CD19 CAR-T therapy between January 2016 and July 2025. Machine learning, logistic regression and cutoff values were utilized to select key variables and develop predictive models. Model performance and clinical applicability were evaluated by receiver operating characteristic, calibration, and clinical decision curves. Survival analyses evaluated the impact of CARAC severity on overall survival (OS) and progression-free survival (PFS) and to validate the prognostic value of the prediction model.</div></div><div><h3>Results</h3><div>Bone marrow (BM) blasts and the modified endothelial activation and stress index (mEASIX) were independent predictors for CARAC. Patients with mEASIX<4.0 were identified as low-risk CARAC. For patients with mEASIX≥4.0, CARAC was stratified by BM blast percentage (blast%). Blast% between 10 % and 44 % indicated high-risk CARAC-nonDIC, and a blast% ≥ 44 % indicated high-risk CARAC-DIC. Moreover, compared to non-CARAC patients, CARAC patients had inferior OS (hazard ratio [HR]: 2.62, <em>p</em> = 0.002) and PFS (HR: 2.11, p = 0.002). The stratified prediction model revealed progressively worse OS and PFS from low-risk CARAC patients to high-risk CARAC-nonDIC, with high-risk CARAC-DIC patients demonstrating the most unfavorable outcomes.</div></div><div><h3>Conclusions</h3><div>An effective CARAC risk prediction and stratification model was established. High-risk CARAC patients, particularly CARAC-DIC, were associated with significantly worse outcomes.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109527"},"PeriodicalIF":3.4,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496851","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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