Pub Date : 2025-04-24DOI: 10.1016/j.thromres.2025.109333
Nao Shimada Ramos, Denise E. Jackson
Haemostasis in Chronic Kidney Disease (CKD) is complex, with patients experiencing both thrombotic and haemorrhagic risks. Current therapies, such as dialysis and blood transfusions, often rely on clinical judgment, which may not fully address these haemostatic abnormalities. This systematic review and meta-analysis aimed to determine whether Thromboelastography (TEG) offers a better ability to assess coagulation abnormalities in CKD compared to standard coagulation tests like activated partial thromboplastin time (aPTT), and prothrombin time (PT). A search across five databases identified 10 studies comparing TEG parameters in CKD patients versus healthy controls. TEG detected hypercoagulability in CKD, with significant reductions in Kinetics Time (P = 0.04), increases in Alpha angles (P = 0.02), and elevated Maximum Amplitude values (P = 0.0006). However, Reaction Time (P = 0.43) and Lysis 30 (P = 0.28) showed no significant differences. Standard coagulation tests, including aPTT and PT, also showed no significant differences between groups (P = 0.30 and P = 1.00), suggesting their limitations in detecting the complex haemostatic changes in CKD. Platelet counts were lower in CKD patients (P = 0.0009) but remained within normal ranges. Elevated fibrinogen levels (P = 0.003), linked to chronic inflammation, indicated a prothrombotic profile. Despite high heterogeneity in some parameters due to variability in CKD stages and treatment types, TEG demonstrates a more detailed assessment of haemostatic changes in CKD, suggesting its potential as a predictive tool for managing coagulation abnormalities.
{"title":"Haemostatic changes detected by thromboelastography in chronic kidney disease: A systematic review and meta-analysis","authors":"Nao Shimada Ramos, Denise E. Jackson","doi":"10.1016/j.thromres.2025.109333","DOIUrl":"10.1016/j.thromres.2025.109333","url":null,"abstract":"<div><div>Haemostasis in Chronic Kidney Disease (CKD) is complex, with patients experiencing both thrombotic and haemorrhagic risks. Current therapies, such as dialysis and blood transfusions, often rely on clinical judgment, which may not fully address these haemostatic abnormalities. This systematic review and meta-analysis aimed to determine whether Thromboelastography (TEG) offers a better ability to assess coagulation abnormalities in CKD compared to standard coagulation tests like activated partial thromboplastin time (aPTT), and prothrombin time (PT). A search across five databases identified 10 studies comparing TEG parameters in CKD patients versus healthy controls. TEG detected hypercoagulability in CKD, with significant reductions in Kinetics Time (P = 0.04), increases in Alpha angles (P = 0.02), and elevated Maximum Amplitude values (P = 0.0006). However, Reaction Time (P = 0.43) and Lysis 30 (P = 0.28) showed no significant differences. Standard coagulation tests, including aPTT and PT, also showed no significant differences between groups (P = 0.30 and P = 1.00), suggesting their limitations in detecting the complex haemostatic changes in CKD. Platelet counts were lower in CKD patients (P = 0.0009) but remained within normal ranges. Elevated fibrinogen levels (P = 0.003), linked to chronic inflammation, indicated a prothrombotic profile. Despite high heterogeneity in some parameters due to variability in CKD stages and treatment types, TEG demonstrates a more detailed assessment of haemostatic changes in CKD, suggesting its potential as a predictive tool for managing coagulation abnormalities.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"250 ","pages":"Article 109333"},"PeriodicalIF":3.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868506","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}
We have conjugated selected number of unfractionated heparin (UFH) chains to human albumin core to mimic mast-cell heparin proteoglycans (HEP-PG). Indeed, APAC, dual antiplatelet and anticoagulant, as HEP-PG, has inhibited collagen- (CIPA) and thrombin-induced platelet aggregation, being simultaneously an anticoagulant. In several animal models of arterial thrombosis, APAC has provided vascular-injury-associated local antithrombotic properties mediated by von Willebrand factor (VWF).
Aims
We compared the structure-function effects of APAC with those of UFH in vitro, and when supplemented in blood studied platelet and VWF-dependency and anticoagulation.
Methods
We assessed the total thrombosis formation analysis system (T-TAS) and coagulation (rotational thromboelastometry, ROTEM) in blood, and thrombin generation and aggregation in platelet-rich plasma. We studied aggregation responses of APAC to collagen, ristocetin, ADP, and potential synergism with cangrelor, P2Y12 receptor antagonist. Finally, heparin-neutralizing role of platelet factor 4 (PF4) on antiplatelet and anticoagulant functions of APAC was investigated.
Results
APAC concentration-dependently exceeded the anticoagulant and antithrombotic action of UFH in ROTEM, and platelet thrombus formation under arterial blood flow over collagen/tissue factor. APAC uniquely inhibited CIPA. While ADP- and ristocetin-induced aggregation were unaffected by APAC, we detected synergism with cangrelor for CIPA. Disruption of the tertiary structure of APAC reverted its mode of action to anticoagulation only, alike UFH. PF4 neutralized antithrombotic actions of APAC.
Conclusion
The structure-function of APAC conveys dual and unique antiplatelet and anticoagulant actions in flowing blood over collagen and beyond. Our studies confirmed the inhibitory role of APAC on VWF functions and fibrin formation.
{"title":"Antiplatelet-anticoagulant, APAC, a mimic of endogenous heparin, is an antithrombotic with von Willebrand factor-mediated characteristics","authors":"Annukka Jouppila , Ilja Nevola , Marja Lemponen , Tomi Mattila , Riitta Lassila","doi":"10.1016/j.thromres.2025.109318","DOIUrl":"10.1016/j.thromres.2025.109318","url":null,"abstract":"<div><h3>Background</h3><div>We have conjugated selected number of unfractionated heparin (UFH) chains to human albumin core to mimic mast-cell heparin proteoglycans (HEP-PG). Indeed, APAC, dual antiplatelet and anticoagulant, as HEP-PG, has inhibited collagen- (CIPA) and thrombin-induced platelet aggregation, being simultaneously an anticoagulant. In several animal models of arterial thrombosis, APAC has provided vascular-injury-associated local antithrombotic properties mediated by von Willebrand factor (VWF).</div></div><div><h3>Aims</h3><div>We compared the structure-function effects of APAC with those of UFH <em>in vitro</em>, and when supplemented in blood studied platelet and VWF-dependency and anticoagulation.</div></div><div><h3>Methods</h3><div>We assessed the total thrombosis formation analysis system (T-TAS) and coagulation (rotational thromboelastometry, ROTEM) in blood, and thrombin generation and aggregation in platelet-rich plasma. We studied aggregation responses of APAC to collagen, ristocetin, ADP, and potential synergism with cangrelor, P2Y12 receptor antagonist. Finally, heparin-neutralizing role of platelet factor 4 (PF4) on antiplatelet and anticoagulant functions of APAC was investigated.</div></div><div><h3>Results</h3><div>APAC concentration-dependently exceeded the anticoagulant and antithrombotic action of UFH in ROTEM, and platelet thrombus formation under arterial blood flow over collagen/tissue factor. APAC uniquely inhibited CIPA. While ADP- and ristocetin-induced aggregation were unaffected by APAC, we detected synergism with cangrelor for CIPA. Disruption of the tertiary structure of APAC reverted its mode of action to anticoagulation only, alike UFH. PF4 neutralized antithrombotic actions of APAC.</div></div><div><h3>Conclusion</h3><div>The structure-function of APAC conveys dual and unique antiplatelet and anticoagulant actions in flowing blood over collagen and beyond. Our studies confirmed the inhibitory role of APAC on VWF functions and fibrin formation.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"250 ","pages":"Article 109318"},"PeriodicalIF":3.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844945","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 : 2025-04-12DOI: 10.1016/j.thromres.2025.109319
Silvia Cardi , Simon Wolf , Riccardo M. Fumagalli , Corrado Lodigiani , Fabian Rössler , Alice Trinchero , Luca Valerio , Walter Ageno , Nils Kucher , Stefano Barco
Background
Splanchnic vein thrombosis (SVT) is a rare form of venous thromboembolism with limited epidemiological data. This study aims to provide a detailed overview in Switzerland using administrative records.
Methods
We analysed nationwide patient-level data on SVT-related hospitalizations, including portal, splenic, and hepatic (Budd-Chiari syndrome) vein thrombosis from 2003 to 2022. We assessed trends in crude and age-standardized incidence rates, proportion of SVT-related hospitalizations, readmission rates as well as gender differences, comorbidities, clinical features, and in-hospital outcomes. Multivariable logistic regression was used to identify predictors of in-hospital death.
Results
SVT was recorded in 17,966 hospitalizations (35 % women) involving 13,689 patients. Portal vein thrombosis was the most frequent manifestation, followed by splenic, hepatic and multisegmental thrombosis. Age-standardized incidence rate increased from 0.4 (95 % CI: 0.3–0.4) per 10,000 general population in 2003 to 1.5 (95 % CI: 1.4–1.6) in 2022, with rising proportions of SVT-related hospitalizations and readmission rates. Case fatality rate remained steady at 13 % and was highest for portal vein thrombosis. For most SVT subtypes, incidence rate was higher in males and case fatality rate in females. Predictors of in-hospital death included liver failure, intestinal infectious diseases, cancer. Common comorbidities included non-neoplastic abdominal diseases (14,010; 78 %), cardiovascular diseases (11,214; 62 %), and cancer (8510; 47 %). Diagnostic or therapeutic procedures involved 56 % of cases, intensive care stay 19 %, and median length of stay was 11 days (Q1-Q3 5–19).
Conclusion
Despite its rarity, SVT is characterized by substantial morbidity and in-hospital mortality. Further research is needed to validate these findings and improve patient management.
{"title":"Splanchnic vein thrombosis (2003−2022): a Swiss nationwide epidemiological study","authors":"Silvia Cardi , Simon Wolf , Riccardo M. Fumagalli , Corrado Lodigiani , Fabian Rössler , Alice Trinchero , Luca Valerio , Walter Ageno , Nils Kucher , Stefano Barco","doi":"10.1016/j.thromres.2025.109319","DOIUrl":"10.1016/j.thromres.2025.109319","url":null,"abstract":"<div><h3>Background</h3><div>Splanchnic vein thrombosis (SVT) is a rare form of venous thromboembolism with limited epidemiological data. This study aims to provide a detailed overview in Switzerland using administrative records.</div></div><div><h3>Methods</h3><div>We analysed nationwide patient-level data on SVT-related hospitalizations, including portal, splenic, and hepatic (Budd-Chiari syndrome) vein thrombosis from 2003 to 2022. We assessed trends in crude and age-standardized incidence rates, proportion of SVT-related hospitalizations, readmission rates as well as gender differences, comorbidities, clinical features, and in-hospital outcomes. Multivariable logistic regression was used to identify predictors of in-hospital death.</div></div><div><h3>Results</h3><div>SVT was recorded in 17,966 hospitalizations (35 % women) involving 13,689 patients. Portal vein thrombosis was the most frequent manifestation, followed by splenic, hepatic and multisegmental thrombosis. Age-standardized incidence rate increased from 0.4 (95 % CI: 0.3–0.4) per 10,000 general population in 2003 to 1.5 (95 % CI: 1.4–1.6) in 2022, with rising proportions of SVT-related hospitalizations and readmission rates. Case fatality rate remained steady at 13 % and was highest for portal vein thrombosis. For most SVT subtypes, incidence rate was higher in males and case fatality rate in females. Predictors of in-hospital death included liver failure, intestinal infectious diseases, cancer. Common comorbidities included non-neoplastic abdominal diseases (14,010; 78 %), cardiovascular diseases (11,214; 62 %), and cancer (8510; 47 %). Diagnostic or therapeutic procedures involved 56 % of cases, intensive care stay 19 %, and median length of stay was 11 days (Q1-Q3 5–19).</div></div><div><h3>Conclusion</h3><div>Despite its rarity, SVT is characterized by substantial morbidity and in-hospital mortality. Further research is needed to validate these findings and improve patient management.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"250 ","pages":"Article 109319"},"PeriodicalIF":3.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864601","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 : 2025-04-04DOI: 10.1016/j.thromres.2025.109317
Bauke Haisma , Sanna R. Rijpma , Marjon H. Cnossen , Paul L. den Exter , Ilmar C. Kruis , Karina Meijer , Laurens Nieuwenhuizen , Nick van Es , Joline L. Saes , Nicole M.A. Blijlevens , Waander L. van Heerde , Saskia E.M. Schols
Introduction
Congenital fibrinogen disorders (CFDs), encompassing quantitative (hypo−/afibrinogenemia) and qualitative (dysfibrinogenemia) defects, can result in bleeding or thrombotic events. This study aimed to enhance understanding of the clinical and genetic characteristics of CFD patients.
Methods
The Dutch cross-sectional RBiN study included 47 CFD patients (median age 38, 55 % women), categorized into (hypo)dysfibrinogenemia, severe (<500 mg/L), moderate (500–1000 mg/L) and mild hypofibrinogenemia (1000–1800 mg/L) as well as carriers with pathogenic variants but normal fibrinogen levels (>1800 mg/L). Clinical assessments included bleeding phenotype, thrombosis history, fibrinogen activity and antigen levels, thrombin and plasmin generation assays and genotypic analysis.
Results
Patients with severe hypofibrinogenemia displayed the highest median ISTH-BAT score (16), followed by moderate hypofibrinogenemia (11), (hypo)dysfibrinogenemia (6), mild hypofibrinogenemia (4) and carriers (0). Female-specific bleeding (postpartum hemorrhage, heavy menstrual bleeding) was prevalent across all CFD subtypes, with moderate hypofibrinogenemia showing high average scores on these ISTH-BAT items (3.0 and 2.3). Postoperative bleeding was common in moderate and severe hypofibrinogenemia (average ISTH-BAT item scores of 2.5 and 2.8, respectively). Patients with biallelic variants had lower fibrinogen activity levels (median 200 mg/L) than those with monoallelic variants (935 mg/L, p < 0.001). Fibrinogen activity levels correlated positively with plasmin peak height (R = 0.74, p < 0.001) and inversely with thrombin potential (R = –0.55, p = 0.002). Thrombin potential was 1.77-fold higher in patients with a venous thrombosis history (n = 5, p = 0.03) than in healthy controls.
Conclusions
In patients with CFDs, postoperative bleeding correlates with fibrinogen activity, while female-specific bleeding affects all CFD subtypes. Elevated thrombin generation might explain thrombosis risk in these patients.
{"title":"Phenotype, genotype, and laboratory assessment of congenital fibrinogen disorders: Data from the Rare Bleeding disorders in the Netherlands study","authors":"Bauke Haisma , Sanna R. Rijpma , Marjon H. Cnossen , Paul L. den Exter , Ilmar C. Kruis , Karina Meijer , Laurens Nieuwenhuizen , Nick van Es , Joline L. Saes , Nicole M.A. Blijlevens , Waander L. van Heerde , Saskia E.M. Schols","doi":"10.1016/j.thromres.2025.109317","DOIUrl":"10.1016/j.thromres.2025.109317","url":null,"abstract":"<div><h3>Introduction</h3><div>Congenital fibrinogen disorders (CFDs), encompassing quantitative (hypo−/afibrinogenemia) and qualitative (dysfibrinogenemia) defects, can result in bleeding or thrombotic events. This study aimed to enhance understanding of the clinical and genetic characteristics of CFD patients.</div></div><div><h3>Methods</h3><div>The Dutch cross-sectional RBiN study included 47 CFD patients (median age 38, 55 % women), categorized into (hypo)dysfibrinogenemia, severe (<500 mg/L), moderate (500–1000 mg/L) and mild hypofibrinogenemia (1000–1800 mg/L) as well as carriers with pathogenic variants but normal fibrinogen levels (>1800 mg/L). Clinical assessments included bleeding phenotype, thrombosis history, fibrinogen activity and antigen levels, thrombin and plasmin generation assays and genotypic analysis.</div></div><div><h3>Results</h3><div>Patients with severe hypofibrinogenemia displayed the highest median ISTH-BAT score (16), followed by moderate hypofibrinogenemia (11), (hypo)dysfibrinogenemia (6), mild hypofibrinogenemia (4) and carriers (0). Female-specific bleeding (postpartum hemorrhage, heavy menstrual bleeding) was prevalent across all CFD subtypes, with moderate hypofibrinogenemia showing high average scores on these ISTH-BAT items (3.0 and 2.3). Postoperative bleeding was common in moderate and severe hypofibrinogenemia (average ISTH-BAT item scores of 2.5 and 2.8, respectively). Patients with biallelic variants had lower fibrinogen activity levels (median 200 mg/L) than those with monoallelic variants (935 mg/L, <em>p</em> < 0.001). Fibrinogen activity levels correlated positively with plasmin peak height (<em>R</em> = 0.74, p < 0.001) and inversely with thrombin potential (R = –0.55, <em>p</em> = 0.002). Thrombin potential was 1.77-fold higher in patients with a venous thrombosis history (<em>n</em> = 5, <em>p</em> = 0.03) than in healthy controls.</div></div><div><h3>Conclusions</h3><div>In patients with CFDs, postoperative bleeding correlates with fibrinogen activity, while female-specific bleeding affects all CFD subtypes. Elevated thrombin generation might explain thrombosis risk in these patients.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109317"},"PeriodicalIF":3.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Von Willebrand factor (VWF) is produced by vascular endothelial cells as large multimers and is cleaved by ADAMTS13 into an appropriate size in a shear stress-dependent manner. Excessive shear stress enhances VWF cleavage, leading to a hemorrhagic disease known as acquired von Willebrand syndrome. No clear reports on the prevalence of the loss of VWF large multimers in patients receiving hemodialysis are currently available. Therefore, this study investigated the prevalence of the loss of VWF large multimers in patients undergoing hemodialysis.
Methods
This single-center, retrospective study involved 90 patients undergoing hemodialysis and 32 healthy participants as controls. VWF antigen levels (VWF:Ag), VWF activity (VWF:RCo), and ADAMTS13 activity were measured. VWF multimer analysis was performed by modified western blotting with an agarose gel electrophoresis, followed by densitometric evaluation of band intensities to calculate the VWF large multimer index (VWF-LMI). A VWF-LMI <80 % was defined as the loss of VWF large multimers, and the prevalence of the loss of VWF large multimers was calculated.
Results
VWF:Ag and VWF:RCo levels in patients undergoing hemodialysis were significantly higher than those in healthy individuals (p < 0.01 both) and were negatively correlated with ADAMTS13 activity (p < 0.01, R = −0.353 and p < 0.01, R = −0.392, respectively). A VWF-LMI <80 % was present in 24 of 90 patients.
Conclusions
The loss of VWF large multimers was identified in 26.7 % of patients receiving hemodialysis. However, the prevalence of the loss of VWF multimers in these patients may be underestimated, as their relatively high VWF activity makes significant bleeding manifestations less likely.
{"title":"Loss of von Willebrand factor large multimers in patients undergoing hemodialysis: A single-center, retrospective study","authors":"Yoshinari Fujii , Satomi Nagaya , Taro Kanno , Shinya Yamada , Misako Suzuki , Kota Goto , Hisanori Horiuchi , Masanori Matsumoto , Eriko Morishita","doi":"10.1016/j.thromres.2025.109316","DOIUrl":"10.1016/j.thromres.2025.109316","url":null,"abstract":"<div><h3>Introduction</h3><div>Von Willebrand factor (VWF) is produced by vascular endothelial cells as large multimers and is cleaved by ADAMTS13 into an appropriate size in a shear stress-dependent manner. Excessive shear stress enhances VWF cleavage, leading to a hemorrhagic disease known as acquired von Willebrand syndrome. No clear reports on the prevalence of the loss of VWF large multimers in patients receiving hemodialysis are currently available. Therefore, this study investigated the prevalence of the loss of VWF large multimers in patients undergoing hemodialysis.</div></div><div><h3>Methods</h3><div>This single-center, retrospective study involved 90 patients undergoing hemodialysis and 32 healthy participants as controls. VWF antigen levels (VWF:Ag), VWF activity (VWF:RCo), and ADAMTS13 activity were measured. VWF multimer analysis was performed by modified western blotting with an agarose gel electrophoresis, followed by densitometric evaluation of band intensities to calculate the VWF large multimer index (VWF-LMI). A VWF-LMI <80 % was defined as the loss of VWF large multimers, and the prevalence of the loss of VWF large multimers was calculated.</div></div><div><h3>Results</h3><div>VWF:Ag and VWF:RCo levels in patients undergoing hemodialysis were significantly higher than those in healthy individuals (<em>p</em> < 0.01 both) and were negatively correlated with ADAMTS13 activity (<em>p</em> < 0.01, R = −0.353 and <em>p</em> < 0.01, R = −0.392, respectively). A VWF-LMI <80 % was present in 24 of 90 patients.</div></div><div><h3>Conclusions</h3><div>The loss of VWF large multimers was identified in 26.7 % of patients receiving hemodialysis. However, the prevalence of the loss of VWF multimers in these patients may be underestimated, as their relatively high VWF activity makes significant bleeding manifestations less likely.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109316"},"PeriodicalIF":3.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748278","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 : 2025-03-29DOI: 10.1016/j.thromres.2025.109313
Alessandro Squizzato , Federica De Pascali , Vittorio Pengo , Marco P. Donadini
{"title":"Efficacy and safety of low-dose acetylsalicylic acid for the prevention of thromboembolic events in individuals positive for antiphospholipid antibodies: A systematic review and meta-analysis","authors":"Alessandro Squizzato , Federica De Pascali , Vittorio Pengo , Marco P. Donadini","doi":"10.1016/j.thromres.2025.109313","DOIUrl":"10.1016/j.thromres.2025.109313","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109313"},"PeriodicalIF":3.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773370","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 : 2025-03-28DOI: 10.1016/j.thromres.2025.109315
Katarzyna Mayger , Johanna Young , Rui Leite , Kiran Parmar , Beverley J. Hunt
Background
Antithrombin signalling may exert an anti-inflammatory effect; therefore we hypothesised that individuals with inherited antithrombin deficiency (ATD) may have an altered inflammatory state.
Aims
To assess the inflammatory state in those with ATD compared with healthy controls (HCs), by measuring inflammatory markers.
Methods
A case-control study of age- and sex-matched HCs (n = 51) with ATD patients (n = 51). Seven inflammatory makers were selected. ELISA assays quantified: high-sensitivity C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and complement C3a-des-Arg. Circulating nucleosomes were measured using a chemiluminescence immunoassay (Nu.Q®NETs). Clauss fibrinogen and HemosIL VWF activity were also measured. Results are expressed as median (range).
Results
Overall analysis of ATD vs HCs showed elevated circulating nucleosomes 29.3 ng/mL [0.5–309.3] vs 21.3 ng/mL [3.7–86.3], p = 0.012 but no differences were observed for C3a, VCAM-1, ICAM-1, VWF and fibrinogen. ATD patients were separated into two groups based on the history of VTE. PF1 + 2 levels were decreased in ATD with previous VTE due to anticoagulation. Increased circulating nucleosomes 38.4 ng/mL [11.6–309.3] vs 24.2 ng/mL [9.3–46.5], p = 0.003 and VCAM-1858.3 ng/mL [564.4–2483.2] vs 746.2 ng/mL [460.6–1034.8], p = 0.016 was observed in ATD with previous VTE vs HCs, respectively. Decreased ICAM-1 and VWF levels were noted in the ATD with no history of VTE when compared to HCs. No significant relationships between AT activity and inflammatory markers were found.
Conclusion
Those with ATD did not have an altered inflammatory state as measured by a group of biomarkers except for increased circulating nucleosomes and VCAM-1 compared to paired healthy controls which can be attributed to previous VTE; while those with no personal history of VTE had reduced ICAM-1 and VWF. No correlation was observed between AT activity and levels of inflammatory markers.
{"title":"Investigation of the impact of antithrombin deficiency on the inflammatory response: Results from a single centre cohort study","authors":"Katarzyna Mayger , Johanna Young , Rui Leite , Kiran Parmar , Beverley J. Hunt","doi":"10.1016/j.thromres.2025.109315","DOIUrl":"10.1016/j.thromres.2025.109315","url":null,"abstract":"<div><h3>Background</h3><div>Antithrombin signalling may exert an anti-inflammatory effect; therefore we hypothesised that individuals with inherited antithrombin deficiency (ATD) may have an altered inflammatory state.</div></div><div><h3>Aims</h3><div>To assess the inflammatory state in those with ATD compared with healthy controls (HCs), by measuring inflammatory markers.</div></div><div><h3>Methods</h3><div>A case-control study of age- and sex-matched HCs (<em>n</em> = 51) with ATD patients (n = 51). Seven inflammatory makers were selected. ELISA assays quantified: high-sensitivity C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and complement C3a-des-Arg. Circulating nucleosomes were measured using a chemiluminescence immunoassay (Nu.Q®NETs). Clauss fibrinogen and HemosIL VWF activity were also measured. Results are expressed as median (range).</div></div><div><h3>Results</h3><div>Overall analysis of ATD vs HCs showed elevated circulating nucleosomes 29.3 ng/mL [0.5–309.3] vs 21.3 ng/mL [3.7–86.3], <em>p</em> = 0.012 but no differences were observed for C3a, VCAM-1, ICAM-1, VWF and fibrinogen. ATD patients were separated into two groups based on the history of VTE. PF1 + 2 levels were decreased in ATD with previous VTE due to anticoagulation. Increased circulating nucleosomes 38.4 ng/mL [11.6–309.3] vs 24.2 ng/mL [9.3–46.5], <em>p</em> = 0.003 and VCAM-1858.3 ng/mL [564.4–2483.2] vs 746.2 ng/mL [460.6–1034.8], <em>p</em> = 0.016 was observed in ATD with previous VTE vs HCs, respectively. Decreased ICAM-1 and VWF levels were noted in the ATD with no history of VTE when compared to HCs. No significant relationships between AT activity and inflammatory markers were found.</div></div><div><h3>Conclusion</h3><div>Those with ATD did not have an altered inflammatory state as measured by a group of biomarkers except for increased circulating nucleosomes and VCAM-1 compared to paired healthy controls which can be attributed to previous VTE; while those with no personal history of VTE had reduced ICAM-1 and VWF. No correlation was observed between AT activity and levels of inflammatory markers.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109315"},"PeriodicalIF":3.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on: “Efficacy and safety of low-dose acetylsalicylic acid for the prevention of thromboembolic events in individuals positive for antiphospholipid antibodies: A systematic review and meta-analysis”","authors":"Shubham Kumar , Nosaibah Razaqi , Rachana Mehta , Ranjana Sah","doi":"10.1016/j.thromres.2025.109312","DOIUrl":"10.1016/j.thromres.2025.109312","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109312"},"PeriodicalIF":3.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748279","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 : 2025-03-26DOI: 10.1016/j.thromres.2025.109314
Jiamei Li , Ruohan Li , Xuting Jin , Jiajia Ren , Jingjing Zhang , Ya Gao , Yanli Hou , Xiaoling Zhang , Gang Wang
Background
The role of longitudinal platelet count trajectories in critically ill patients with thrombocytopenia is unclear. This study aimed to identify the association between trajectory patterns and prognosis and assess whether these patterns could enhance the predictive capability of Acute Physiology and Chronic Health Evaluation (APACHE) IV or Sequential Organ Failure Assessment (SOFA) scores for mortality.
Methods
This retrospective cohort study employed latent growth mixture modeling (LGMM) to identify platelet count trajectory patterns. Cox proportional hazards model was used to evaluate the association between the patterns and mortality. Receiver Operating Characteristic (ROC) curves were plotted, and the areas under the curves (AUCs) were compared between models using the APACHE IV or SOFA score alone and those incorporating trajectory patterns.
Results
A total of 1683 patients from the eICU Collaborative Research Database (eICU-CRD) and 931 patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were included. Two trajectory patterns were identified: Class 1, characterized by “Gradual increase,” and Class 2, with “Persistent low.” Patients in Class 2 had higher ICU mortality (eICU-CRD: 2.273[1.457–3.546]; MIMIC-IV database: 1.991[1.162–3.412]). Incorporating trajectory patterns into the APACHE IV or SOFA scores substantially enhanced the AUC of these scoring systems alone in predicting ICU mortality (eICU-CRD: P < 0.001; MIMIC-IV database: P = 0.0018).
Conclusion
The longitudinal platelet count trajectory patterns are complementary predictors of survival in critically ill patients with thrombocytopenia. Persistently low platelet counts are significantly associated with unfavorable clinical outcomes.
{"title":"Platelet count trajectory patterns and prognosis in critically ill patients with thrombocytopenia: Based on latent growth mixture model analysis","authors":"Jiamei Li , Ruohan Li , Xuting Jin , Jiajia Ren , Jingjing Zhang , Ya Gao , Yanli Hou , Xiaoling Zhang , Gang Wang","doi":"10.1016/j.thromres.2025.109314","DOIUrl":"10.1016/j.thromres.2025.109314","url":null,"abstract":"<div><h3>Background</h3><div>The role of longitudinal platelet count trajectories in critically ill patients with thrombocytopenia is unclear. This study aimed to identify the association between trajectory patterns and prognosis and assess whether these patterns could enhance the predictive capability of Acute Physiology and Chronic Health Evaluation (APACHE) IV or Sequential Organ Failure Assessment (SOFA) scores for mortality.</div></div><div><h3>Methods</h3><div>This retrospective cohort study employed latent growth mixture modeling (LGMM) to identify platelet count trajectory patterns. Cox proportional hazards model was used to evaluate the association between the patterns and mortality. Receiver Operating Characteristic (ROC) curves were plotted, and the areas under the curves (AUCs) were compared between models using the APACHE IV or SOFA score alone and those incorporating trajectory patterns.</div></div><div><h3>Results</h3><div>A total of 1683 patients from the eICU Collaborative Research Database (eICU-CRD) and 931 patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were included. Two trajectory patterns were identified: Class 1, characterized by “Gradual increase,” and Class 2, with “Persistent low.” Patients in Class 2 had higher ICU mortality (eICU-CRD: 2.273[1.457–3.546]; MIMIC-IV database: 1.991[1.162–3.412]). Incorporating trajectory patterns into the APACHE IV or SOFA scores substantially enhanced the AUC of these scoring systems alone in predicting ICU mortality (eICU-CRD: <em>P</em> < 0.001; MIMIC-IV database: <em>P</em> = 0.0018).</div></div><div><h3>Conclusion</h3><div>The longitudinal platelet count trajectory patterns are complementary predictors of survival in critically ill patients with thrombocytopenia. Persistently low platelet counts are significantly associated with unfavorable clinical outcomes.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"249 ","pages":"Article 109314"},"PeriodicalIF":3.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号