Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Andexanet alfa: trials just leave us with more questions","authors":"Richard J. Buka","doi":"10.1016/j.rpth.2024.102628","DOIUrl":"10.1016/j.rpth.2024.102628","url":null,"abstract":"<div><div>Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor (ANNEXA-I), the first ever randomized controlled trial of a reversal agent for direct oral anticoagulants, was published in 2024. The trial, which randomized patients with intracranial hemorrhage to andexanet alfa or usual care, was mandated by the United States Food and Drug Administration as part of its conditional approval in 2018. This approval was originally based on the single-arm trial, The Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4). ANNEXA-I was stopped early for benefit and showed a reduction in the number of patients with significant hematoma expansion. However, the study was not powered for clinical endpoints such as disability or death and showed no difference in these outcomes. It did, however, show an increased risk of thrombosis, predominantly stroke with andexanet alfa. In this perspective, I reflect on some of the key criticisms of the trial and the implications for its interpretation.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102628"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transfusion in trauma: empiric or guided therapy?","authors":"Liam Barrett ,&nbsp;Nicola Curry","doi":"10.1016/j.rpth.2024.102663","DOIUrl":"10.1016/j.rpth.2024.102663","url":null,"abstract":"<div><div>A state of the art lecture titled “Transfusion therapy in trauma—what to give? Empiric vs guided” was presented at the International Society on Thrombosis and Haemostasis Congress in 2024. Uncontrolled bleeding is the commonest preventable cause of death after traumatic injury. Hemostatic resuscitation is the foundation of contemporary transfusion practice for traumatic bleeding and has 2 main aims: to immediately support the circulating blood volume and to treat/prevent the associated trauma-induced coagulopathy. There are 2 broad types of hemostatic resuscitation strategy: empiric ratio-based therapy, often using red blood cells and fresh frozen plasma in a 1:1 ratio, and targeted therapy where the use of platelets, plasma, or fibrinogen is guided by laboratory or viscoelastic hemostatic tests. There are benefits, and limitations, to each strategy and neither approach has yet been shown to improve outcomes across all patient groups. Questions remain, and future directions for improving transfusion therapy are likely to require novel approaches that have greater flexibility to evaluate and treat heterogeneous trauma cohorts. Such approaches may include the integration of machine learning technologies in clinical systems, with real-time linkage of clinical and laboratory data, to aid early recognition of patients at the greatest risk of bleeding and to direct and individualize transfusion therapies. Greater mechanistic understanding of the underlying pathobiology of trauma-induced coagulopathy and the direct effects of common treatments on this process will be of equal importance to the development of new treatments. Finally, we summarize relevant new data on this topic presented at the 2024 ISTH Congress.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102663"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humans","authors":"Chih Jen Yang ,&nbsp;Lyndsey E. Shorey-Kendrick ,&nbsp;Cristina Puy ,&nbsp;Ashley E. Benson ,&nbsp;Phillip A. Wilmarth ,&nbsp;Ashok P. Reddy ,&nbsp;Keith D. Zientek ,&nbsp;Kilsun Kim ,&nbsp;Adam Crosland ,&nbsp;Chaevien S. Clendinen ,&nbsp;Lisa M. Bramer ,&nbsp;Olivia L. Hagen ,&nbsp;Helen H. Vu ,&nbsp;Joseph E. Aslan ,&nbsp;Owen J.T. McCarty ,&nbsp;Joseph J. Shatzel ,&nbsp;Brian P. Scottoline ,&nbsp;Jamie O. Lo","doi":"10.1016/j.rpth.2024.102676","DOIUrl":"10.1016/j.rpth.2024.102676","url":null,"abstract":"<div><h3>Background</h3><div>Amniotic fluid (AF) plays a key role in fetal development, yet the evolving composition of AF and its effects on hemostasis and thrombosis are poorly understood.</div></div><div><h3>Objectives</h3><div>To characterize the procoagulant properties of AF as a function of gestation in humans and nonhuman primates.</div></div><div><h3>Methods</h3><div>We analyzed the proteomes, lipidomes, and procoagulant properties of AF obtained by amniocentesis from rhesus macaque and human pregnancies at gestational age-matched time points.</div></div><div><h3>Results</h3><div>When added to human plasma, both rhesus and human AF accelerated clotting time and fibrin generation. We identified proteomic modules associated with clotting time and enriched for coagulation-related pathways. Proteins known to be involved in hemostasis were highly correlated with each other, and their intensity of expression varied across gestation in both rhesus and humans. Inhibition of the contact pathway did not affect the procoagulant effect of AF. Blocking tissue factor pathway inhibitor reversed the ability of AF to block the generation of activated factor X. The prothrombinase activity of AF was inhibited by phospholipid inhibitors. The levels of phosphatidylserine in AF were inversely correlated with clotting time. AF promoted platelet activation and secretion in plasma.</div></div><div><h3>Conclusion</h3><div>Overall, our findings reveal that the addition of AF to plasma enhances coagulation in a manner dependent on phospholipids as well as the presence of proteases and other proteins that directly regulate coagulation. We describe a correlation between clotting time and expression of coagulation proteins and phosphatidylserine in both rhesus and human AF, supporting the use of rhesus models for future studies of AF biology.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102676"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutation","authors":"Serge Pierre-Louis ,&nbsp;Johalene Rabout ,&nbsp;Octavio Labrada ,&nbsp;Fatima Radouani ,&nbsp;Emeline Chonville ,&nbsp;Beatrice Ferrey ,&nbsp;Olivier Pierre-Louis ,&nbsp;Yesim Dargaud","doi":"10.1016/j.rpth.2025.102678","DOIUrl":"10.1016/j.rpth.2025.102678","url":null,"abstract":"<div><h3>Background</h3><div>The bleeding disorder described here is due to a heterozygous autosomal dominant C1611&gt;A variant in the thrombomodulin (TM) gene that significantly elevates plasma TM levels, which enhances the activation of protein C. This activation inhibits factors VIIIa and Va, reducing thrombin generation and potentially leading to severe hemorrhagic manifestations.</div></div><div><h3>Key Clinical Question</h3><div>What is the bleeding profile of patients with this rare condition? What are the most frequent clinical signs, and how can they be treated?</div></div><div><h3>Clinical Approach</h3><div>We present a case study of an index patient with the <em>TM</em> C1611&gt;A variant and his 20 family members. We detail the hemostatic strategies employed during various bleeding episodes and surgical procedures.</div></div><div><h3>Conclusion</h3><div>Sharing clinical experiences is crucial for hematologists managing similar cases, as it provides valuable insights into effective treatment strategies.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102678"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world andexanet alfa utilization and the association between delay in administration due to hospital transfer and all-cause inpatient mortality","authors":"Huiqiao Fan,&nbsp;Youssef Bessada,&nbsp;Craig I. Coleman","doi":"10.1016/j.rpth.2025.102688","DOIUrl":"10.1016/j.rpth.2025.102688","url":null,"abstract":"<div><h3>Background</h3><div>Evaluations of andexanet alfa for the reversal of factor Xa inhibitor-associated bleeding have been small, with cohorts drawn from single/limited sites. Delays in providing anticoagulation reversal due to hospital transfer may result in poorer outcomes.</div></div><div><h3>Objectives</h3><div>To describe the characteristics and outcomes of andexanet alfa users and evaluate the association between delay in andexanet alfa administration due to transfer from a different acute care hospital and the incidence of all-cause inpatient mortality.</div></div><div><h3>Methods</h3><div>This was a retrospective study using National Inpatient Sample data. Hospitalizations with procedural codes for andexanet alfa and a billing code for bleeding were included. Descriptive analysis was performed, as was multivariable logistic regression, to estimate the odds ratio and 95% CI for the association between andexanet alfa delayed due to transfer from a different acute care hospital and all-cause inpatient mortality.</div></div><div><h3>Results</h3><div>From 2019 to 2021, 4210 hospitalizations occurred in adults receiving andexanet alfa and a bleed. Most were hospitalized with intracranial hemorrhage (62.0%). The incidence of all-cause inpatient mortality was 16.6% (95% CI, 14.3%-19.3%), mean hospital stays lasted 9.1 days (95% CI, 8.4-9.8), and mean hospital costs were $73,600 (95% CI, $65,000-$82,200). Of all cases, 18.5% were transferred from a different acute care hospital prior to receiving andexanet alfa. Cases with hospital transfer had an 82% increased odds of all-cause inpatient mortality (95% CI, 17%-183%) but did not reach statistical significance when the population was limited to intracranial hemorrhage (odds ratio, 1.51; 95% CI, 0.88-2.60).</div></div><div><h3>Conclusion</h3><div>Delay in administering andexanet alfa due to hospital transfer may be associated with increased all-cause mortality.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102688"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription factor RUNX1 regulates coagulation factor XIII-A (F13A1): decreased platelet-megakaryocyte F13A1 expression and clot contraction in RUNX1 haplodeficiency","authors":"Fabiola Del Carpio-Cano ,&nbsp;Natthapol Songdej ,&nbsp;Liying Guan ,&nbsp;Guangfen Mao ,&nbsp;Lawrence E. Goldfinger ,&nbsp;Jeremy G.T. Wurtzel ,&nbsp;Kiwon Lee ,&nbsp;Michele P. Lambert ,&nbsp;Mortimer Poncz ,&nbsp;A. Koneti Rao","doi":"10.1016/j.rpth.2025.102680","DOIUrl":"10.1016/j.rpth.2025.102680","url":null,"abstract":"<div><h3>Background</h3><div>Germline <em>RUNX1</em> haplodeficiency (RHD) is associated with thrombocytopenia, platelet dysfunction, and predisposition to myeloid malignancies. Platelet expression profiling of an RHD patient showed decreased <em>F13A1</em>, encoding for the A subunit of factor (F)XIII<em>,</em> a transglutaminase that cross-links fibrin and induces clot stabilization. FXIII-A is synthesized by hematopoietic cells, megakaryocytes, and monocytes.</div></div><div><h3>Objectives</h3><div>To understand RUNX1 regulation of <em>F13A1</em> expression in platelets/megakaryocytes and the mechanisms and consequences of decreased <em>F13A1</em> in RHD.</div></div><div><h3>Methods</h3><div>We performed studies in platelets, human erythroleukemia (HEL) cells, and human CD34+ cell-derived megakaryocytes including on clot contraction in cells following small inhibitor RNA knockdown (KD) of RUNX1 or F13A1.</div></div><div><h3>Results</h3><div>Platelet <em>F13A1</em> mRNA and protein were decreased in our index patient and in 2 siblings from an unrelated family with RHD. Platelet-driven clot contraction was decreased in the patient and affected daughter. Promoter studies in HEL cells showed that <em>RUNX1</em> regulates <em>F13A1</em> transcription<em>;</em> RUNX1 overexpression increased, and small inhibitor RNA RUNX1 KD reduced <em>F13A1</em> promoter activity and protein. Following <em>RUNX1</em> or <em>F13A1</em> KD, clot contraction by HEL cells was decreased, as were FXIII-A surface expression, myosin light chain phosphorylation, and PAC1 antibody binding upon activation. <em>F13A1</em> expression and clot contraction were impaired in <em>RUNX1</em> downregulation in human megakaryocytes.</div></div><div><h3>Conclusion</h3><div>RUNX1 regulates platelet-megakaryocyte <em>F13A1</em> expression, which is decreased in RHD, reflecting regulation of a coagulation protein by a hematopoietic transcription factor. Platelet and megakaryocyte clot contraction is decreased in RHD, related to multiple impaired mechanisms including <em>F13A1</em> expression<em>,</em> myosin phosphorylation, and α_IIbβ₃ activation.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102680"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143369823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural bioinformatics for rational drug design","authors":"Soroush Mozaffari ,&nbsp;Agnethe Moen ,&nbsp;Che Yee Ng ,&nbsp;Gerry A.F. Nicolaes ,&nbsp;Kanin Wichapong","doi":"10.1016/j.rpth.2025.102691","DOIUrl":"10.1016/j.rpth.2025.102691","url":null,"abstract":"<div><div>A State of the Art lecture titled “structural bioinformatics technologies for rational drug design: from in silico to in vivo” was presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in 2024. Drug discovery remains a resource-intensive and complex endeavor, which usually takes over a decade and costs billions to bring a new therapeutic agent to market. However, the landscape of drug discovery has been transformed by the recent advancements in bioinformatics and cheminformatics. Key techniques, including structure- and ligand-based virtual screening, molecular dynamics simulations, and artificial intelligence–driven models are allowing researchers to explore vast chemical spaces, investigate molecular interactions, predict binding affinity, and optimize drug candidates with unprecedented accuracy and efficiency. These computational methods complement experimental techniques by accelerating the identification of viable drug candidates and refining lead compounds. Artificial intelligence models, alongside traditional physics-based simulations, now play an important role in predicting key properties such as binding affinity and toxicity, contributing to more informed decision-making, particularly early in the drug discovery process. Despite these advancements, challenges remain in terms of accuracy, interpretability, and the needed computational power. This review explores the state of the art in computational drug discovery, examining the latest methods and technologies, their transformative impact on the drug development pipeline, and the future directions needed to overcome remaining limitations. Finally, we summarize relevant data and highlight cases where various computational approaches were successfully applied to develop novel inhibitors, as presented during the ISTH 2024 Congress.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102691"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the 5-SNP score for the prediction of venous thromboembolism in a Danish fast-track cohort of 6789 total hip and total knee arthroplasty patients","authors":"Mark J.R. Smeets ,&nbsp;Pelle B. Petersen ,&nbsp;Christoffer C. Jørgensen ,&nbsp;Suzanne C. Cannegieter ,&nbsp;Sisse R. Ostrowski ,&nbsp;Henrik Kehlet ,&nbsp;Banne Nemeth","doi":"10.1016/j.rpth.2024.102644","DOIUrl":"10.1016/j.rpth.2024.102644","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE) is a serious complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Despite improvements with fast-track treatment protocols, 0.5% of patients still develop a VTE within 90-days postoperatively. Previously, the 5-single nucleotide polymorphism (SNP) genetic risk scores (weighted and simplified) were developed to identify people at a high risk for VTE within the general population.</div></div><div><h3>Objectives</h3><div>We aimed to assess whether the 5-SNP scores could be used to identify high-risk patients in a cohort of fast-track THA/TKA patients.</div></div><div><h3>Methods</h3><div>A subset of patients from the Lundbeck Centre for Fast-track Hip and Knee Replacement Database was included based on the availability of genetic information. The 5-SNP scores were calculated for these patients, and their discriminatory performance was determined by c-statistic. Furthermore, the 5-SNP scores were added to a simple logistic prediction model containing clinical predictors to assess the added predictive value.</div></div><div><h3>Results</h3><div>A total of 7753 THA and TKA procedures (6798 patients) were included in this study. The c-statistics for the weighted and simple 5-SNP scores were 0.50 (95% CI, 0.39-0.61) and 0.48 (95% CI, 0.38-0.58), respectively. For the model with clinical predictors, the c-statistic was 0.67 (95% CI, 0.56-0.77). Addition of either of the 5-SNP scores did not improve discrimination in this model.</div></div><div><h3>Conclusion</h3><div>These findings do not support genetic risk profiling in fast-track THA/TKA patients to predict VTE. Hence, efforts should be directed at optimizing prediction models with clinical predictors.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102644"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylactic use of recombinant ADAMTS-13 during pregnancy for congenital thrombotic thrombocytopenic purpura","authors":"Éloïse Colliou ,&nbsp;Agnès Ribes ,&nbsp;Clotilde Gaible ,&nbsp;Mathilde Marlas ,&nbsp;David Ribes ,&nbsp;Isabelle Labadens ,&nbsp;Paul Guerby ,&nbsp;Stanislas Faguer","doi":"10.1016/j.rpth.2025.102687","DOIUrl":"10.1016/j.rpth.2025.102687","url":null,"abstract":"<div><h3>Background</h3><div>Congenital thrombotic thrombocytopenic purpura (cTTP) related to ADAMTS-13 deficiency is associated with a maternal risk of death of 10% and a risk of fetal loss greater than 50% without treatment.</div></div><div><h3>Key Clinical Question</h3><div>Is prophylactic use of recombinant (r)ADAMTS-13 during pregnancy in patients with cTTP safe and effective in preventing cTTP relapse?</div></div><div><h3>Clinical Approach</h3><div>rADAMTS-13 was given intravenously weekly (40 Units/kg) from 17 weeks’ gestation. ADAMTS-13 activity was undetectable before the first administration, reached 60% to 90% of normal levels 2 hours after, and became undetectable between days 4 and 6. A full dose was given in the hours preceding the delivery and on day 3. No flare-up of cTTP occurred during the pregnancy, and rADAMTS-13 was tolerated well. No anti–ADAMTS-13 antibodies developed.</div></div><div><h3>Conclusion</h3><div>Prophylactic use of rADAMTS-13 during pregnancy may prevent relapse of cTTP and reduce the risk of fetal loss, but an optimal regimen requires further attention.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102687"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143295797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease","authors":"Fien A. von Meijenfeldt ,&nbsp;Ton Lisman ,&nbsp;Alessandra Pacheco ,&nbsp;Yoh Zen ,&nbsp;William Bernal","doi":"10.1016/j.rpth.2024.102666","DOIUrl":"10.1016/j.rpth.2024.102666","url":null,"abstract":"<div><h3>Background</h3><div>Liver disease is often characterized by the activation of coagulation and inflammation. Experimental studies suggest that the interaction between neutrophils and platelets with local activation of coagulation could contribute to liver injury progression, but there have been limited studies in humans.</div></div><div><h3>Objectives</h3><div>We studied the hemostatic components and neutrophil extracellular traps (NETs) in liver biopsies from patients with different inflammatory liver diseases.</div></div><div><h3>Methods</h3><div>Liver biopsies from patients with inflammatory liver disease (alcoholic steatohepatitis [ASH], autoimmune hepatitis, primary sclerosing cholangitis, metabolic-associated steatohepatitis, and allograft ischemia-reperfusion injury (IRI), each <em>n</em> = 20) were stained for fibrin(ogen), platelets, and NETs. The correlation of NET formation with deposition of hemostatic components and laboratory measures of disease severity was investigated.</div></div><div><h3>Results</h3><div>In 75% of the liver biopsies, no fibrin(ogen) was detectable, and only 20% of the biopsies showed minimal deposition. Overall, 50% of liver biopsies stained positive for NETs. Platelet deposition and NET formation were highest in IRI, where it correlated with histologic severity of injury (r = .61 [95% CI, .22-.84]; <em>P</em> &lt; .01) and ASH. Platelet deposition was associated with NET formation (r = .44 [95% CI, .27-.59]; <em>P</em> &lt; .001) and colocalized in the biopsies. NET formation, but not fibrin and platelet deposition, was moderately associated with the model of end-stage liver disease score (r = .29 [95% CI, .07-.49]; <em>P</em> &lt; .01).</div></div><div><h3>Conclusion</h3><div>In contrast to experimental studies, we demonstrated minimal intrahepatic fibrin(ogen) deposition in different types of human inflammatory liver disease. Histologic evidence for intrahepatic NETs was common and most pronounced in acute ASH and IRI and was associated with platelet deposition and disease severity.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102666"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156206","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}