Journal of Thrombosis and Haemostasis最新文献

{"title":"Long-term FXa inhibition attenuates thromboinflammation after acute myocardial infarction and stroke by platelet proteome alteration.","authors":"Amin Polzin, Marcel Benkhoff, Manuela Thienel, Maike Barcik, Philipp Mourikis, Khrystyna Shchurovska, Carolin Helten, Vincent Ehreiser, Zhang Zhe, Franziska von Wulffen, Alexander Theiss, Sameera Peri, Sophie Cremer, Samantha Ahlbrecht, Saif Zako, Laura Wildeis, Gabrielle Al-Kassis, Daniel Metzen, Amelie Utz, Hao Hu, Lilian Vornholz, Goran Pavic, Enzo Lüsebrink, Jan Strecker, Steffen Tiedt, Mareike Cramer, Michael Gliem, Tobias Ruck, Sven G Meuth, Tobias Zeus, Christoph Mayr, Herbert B Schiller, Lukas Simon, Steffen Massberg, Malte Kelm, Tobias Petzold","doi":"10.1016/j.jtha.2024.10.025","DOIUrl":"10.1016/j.jtha.2024.10.025","url":null,"abstract":"<p><strong>Background: </strong>Immediate activated factor (F)X (FXa) inhibition exerts direct antiplatelet effects in the context of arterial thrombosis but little is known about the impact of long-term therapy on platelet function in ischemic cardiovascular diseases.</p><p><strong>Objectives: </strong>Therefore, we analyzed platelet-derived effects of long-term FXa inhibition in the setting of acute myocardial infarction (AMI) and stroke.</p><p><strong>Methods: </strong>We evaluated the effect of acute versus chronic FXa inhibition on thromboinflammation following AMI and stroke in mice in vivo. Mechanistically, we identified changes in platelet gene expression and proteome under chronic FXa nonvitamin K antagonist oral anticoagulant treatment and characterized its functional consequence on platelet physiology. In a prospectively recruited cohort of patients with AMI, we determined cardiovascular magnetic resonance based cardiac endpoints under FXa nonvitamin K antagonist oral anticoagulant effects on clinical endpoints in a cohort of patients with AMI.</p><p><strong>Results: </strong>Chronic but not acute FXa inhibition reduced cerebral and myocardial infarct size and improved cardiac function 24 hours after AMI in mice. Mechanistically, we identified an attenuated thromboinflammatory response with reduced neutrophil extracellular trap formation in mice and patient samples. Proteome and RNA expression analysis of FXa inhibitor treated patients revealed a reduction of key regulators within the membrane trafficking and secretion machinery hampering platelet α and dense granule release. Subsequent, thromboinflammatory neutrophil extracellular trap density in thrombi isolated from stroke and myocardial infarction patients was reduced. Patients with AMI treated with FXa inhibitors showed decreased infarct size after myocardial infarction compared to patients without anticoagulation treatment.</p><p><strong>Conclusion: </strong>Long-term FXa inhibition induces antithromboinflammatory proteome signatures in platelets, improving infarct size after myocardial infarction and stroke.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bortezomib for rituximab-refractory immune-mediated thrombotic thrombocytopenic purpura in the caplacizumab era: an Italian multicenter study.","authors":"Juri Alessandro Giannotta, Andrea Artoni, Ilaria Mancini, Pasquale Agosti, Monica Carpenedo, Addolorata Truma, Syna Miri, Barbara Ferrari, Pasqualina De Leo, Prassede Salutari, Giorgia Mancini, Alfredo Molteni, Ermina Rinaldi, Monica Bocchia, Mariasanta Napolitano, Lucia Prezioso, Annarosa Cuccaro, Elisabetta Scarpa, Annalisa Condorelli, Daniele Grimaldi, Massimo Massaia, Flora Peyvandi","doi":"10.1016/j.jtha.2024.10.034","DOIUrl":"10.1016/j.jtha.2024.10.034","url":null,"abstract":"<p><strong>Background: </strong>Immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients are not responsive to standard rituximab in approximately 10% to 15% of cases, and oral immunosuppressants showed controversial results with significant toxicity. Targeting plasma cells with bortezomib appears promising, but the available evidence is scarce and stems only from isolated reports in the precaplacizumab era.</p><p><strong>Objectives: </strong>To evaluate the safety and efficacy of bortezomib in rituximab-refractory iTTP patients.</p><p><strong>Methods: </strong>We conducted a retrospective observational multicenter study among 13 Italian iTTP treating centers, collecting data from May 2017 to May 2023 (caplacizumab was licensed in Italy in January 2020).</p><p><strong>Results: </strong>Bortezomib was effective in 10/17 patients (59%). Eleven were treated in the acute phase (9/11 responders, 82%, allowing discontinuation of caplacizumab in 5/6 treated patients), and 7 during clinical remission (2/7 responders, 28%). Responses occurred at a median time of 30 days, but 3 patients responded after 4 months. The median duration of response was 22 months (IQR, 10-38), still ongoing in 6 patients at the time of data cutoff. Responders had fewer previous acute iTTP episodes than nonresponders (median [IQR], 1 [1,2] vs 5.5 [2-7]; P = .03). Eight subjects (47%) reported toxicities, mostly in those treated with ≥2 cycles.</p><p><strong>Conclusion: </strong>Durable responses to bortezomib were registered in about 60% of multirefractory iTTP patients with mild to moderate toxicities. The occurrence of late responses (ie, after 30 days) suggests a \"watchful waiting\" approach after bortezomib treatment.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biophysical characterization of blood coagulation factor VIII binding to lipid nanodiscs that mimic activated platelet surfaces.","authors":"Nathan G Avery, Isabelle R Young, Selena Lu, Jordan D Vaughan, Patrick S Korus, Tera N Richardson, Kenneth C Childers, Serge L Smirnov, P Clint Spiegel","doi":"10.1016/j.jtha.2024.11.003","DOIUrl":"10.1016/j.jtha.2024.11.003","url":null,"abstract":"<p><strong>Background: </strong>Following proteolytic activation, activated blood coagulation factor (F)VIII (FVIIIa) binds to activated platelet membranes, forming the intrinsic tenase complex with activated FIX (FIXa). Previous studies have identified the C1 and C2 domains as the membrane binding domains of FVIII through conserved arginine residues. A membrane binding model for the FVIII C domains proposes that surface-exposed hydrophobic and positively charged residues at each C domain interact with the membrane, yet a comprehensive thermodynamic and structural description of this interaction is lacking.</p><p><strong>Objectives: </strong>To determine residues of interaction, thermodynamics, and membrane binding preference for FVIII membrane association.</p><p><strong>Methods: </strong>The binding of FVIII constructs to lipid nanodiscs was characterized by nuclear magnetic resonance, isothermal titration calorimetry, bio-layer interferometry, and X-ray crystallography.</p><p><strong>Results: </strong>The thermodynamics of FVIII membrane binding indicated that the C1 domain associates through an enthalpically driven process while the C2 domain is entropically driven. Alanine mutations to surface-exposed hydrophobic residues in the C2 domain revealed differential effects on membrane binding, highlighting important determinants at the residue level. The structure of a C2 double mutant, L2251A/L2252A, demonstrated that its decreased affinity is likely due to decreasing the surface area hydrophobicity. Nuclear magnetic resonance studies with the C2 domain identified residues of interaction with soluble O-phospho-L-serine as well as lipid nanodiscs. Lastly, increasing phosphatidylethanolamine and decreasing phosphatidylserine content decreased overall FVIII affinity for membrane surfaces.</p><p><strong>Conclusion: </strong>This study provides further insight into the molecular basis for how FVIII interacts with platelets to form the intrinsic tenase complex.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catheter-related thrombosis in adults with cancer: a secondary analysis of a prospective randomized controlled trial.","authors":"Greg Hapgood, Kate Hill, Satomi Okano, Emad Abro, David Looke, Glen Kennedy, Gilbert Pavilion, Rosita Van Kuilenburg, Alanna Geary, Warren Joubert, Melissa Eastgate, Mark Jones, Peter Mollee","doi":"10.1016/j.jtha.2024.11.002","DOIUrl":"10.1016/j.jtha.2024.11.002","url":null,"abstract":"<p><strong>Background: </strong>Catheter-related thrombosis (CRT) is a complication of central venous access devices (CVADs). Evidence is variable regarding the significance of the side of catheter insertion. The role of the patient's hand dominance in predisposition to CRT remains uncertain.</p><p><strong>Objectives: </strong>In a prospective randomized controlled trial, adult cancer patients were randomly allocated to either dominant or nondominant side CVAD insertion. The primary endpoint of this trial examined the incidence of catheter-associated bloodstream infection. Here, we report the secondary endpoint of the incidence of CRT.</p><p><strong>Methods: </strong>Six hundred forty CVADs were randomized to the dominant (n = 322) or nondominant (n = 318) side of insertion. Only symptomatic patients underwent ultrasound imaging to evaluate for CRT.</p><p><strong>Results: </strong>The median patient age was 58 years, 60% of patients had hematologic malignancies and 40% had solid tumors. CVADs used were peripherally-inserted central catheter line (67%), tunneled CVAD (23%), or nontunneled CVAD (10%). The CRT incidence rate was 0.65 versus 0.82 per 1000 line days in the dominant versus nondominant group (hazard ratio [HR], 1.2; 95% CI, 0.58-2.48; P = .63). There was no significant difference in CRT incidence rate between left- and right-sided insertions (HR, 0.63; 95% CI, 0.30-1.32; P = .22). The CRT incidence rate was lower in right-handed versus left-handed line inserters (HR, 0.29; 95% CI, 0.12-0.71; P = .007).</p><p><strong>Conclusion: </strong>The rate of CRT was not associated with whether CVAD insertion was on the patient's dominant or nondominant side or the side of insertion. The role of inserter hand dominance requires further investigation.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning models for risk prediction of cancer-associated thrombosis: a systematic review and meta-analysis.","authors":"Keya Chen, Ying Zhang, Lufang Zhang, Wei Zhang, Yu Chen","doi":"10.1016/j.jtha.2024.11.001","DOIUrl":"10.1016/j.jtha.2024.11.001","url":null,"abstract":"<p><strong>Background: </strong>Although the number of models for predicting the risk of cancer-associated thrombosis has been rising, there is still a lack of comprehensive assessment for machine learning prediction models.</p><p><strong>Objectives: </strong>This study aimed to critically appraise and quantify the performance studies using machine learning to predict cancer-associated thrombosis.</p><p><strong>Methods: </strong>We conducted searches on PubMed, Embase, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and other related databases for the related publications (from inception to December 1, 2023). The Prediction Model Risk of Bias Assessment Tool checklist was employed to evaluate the risk of bias and applicability. The Grading of Recommendations Assessment, Development and Evaluation system was used to evaluate the quality of evidence in systematic reviews. Meta-analyses were conducted using R (version 4.3.2).</p><p><strong>Results: </strong>A total of 32 studies were included. Mostly included literature exhibited a high risk of bias, and the applicability of the prediction models was deemed acceptable. The 21 included studies in the meta-analysis demonstrated the high predictive capacity of the machine learning models for cancer-associated thrombosis.</p><p><strong>Conclusion: </strong>Most of the prediction models included in the study showed good applicability and excellent prediction performance, but there was a high risk of bias.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of platelet transcriptomics for assessing treatment effectiveness and predicting long-term platelet counts recovery in aplastic anemia.","authors":"Jin Mao, Jingyu Zhao, Hong Pan, Zhen Gao, Lele Zhang, Weiwang Li, Liwei Fang, Cuicui Liu, Pei Su, Hongtao Wang, Jiaxi Zhou, Jun Shi","doi":"10.1016/j.jtha.2024.10.032","DOIUrl":"10.1016/j.jtha.2024.10.032","url":null,"abstract":"<p><strong>Background: </strong>Aplastic anemia (AA) is a bone marrow failure disease for which the means of assessing and predicting the therapeutic effectiveness are still relatively limited. Thrombocytopenia is often the earliest and most severe symptom in patients newly diagnosed with AA. While clinical consideration is usually given to the quantitative changes in platelets during treatment, there is little focus on the resolution of the molecular characteristics of platelets in AA.</p><p><strong>Objectives: </strong>To investigate the changes in platelet molecular characteristics throughout the treatment process of AA, and to explore the use of transcriptomics for monitoring and predicting treatment outcomes.</p><p><strong>Methods: </strong>We comprehensively analyzed platelet transcriptomic changes in patients with AA at initial diagnosis and different stages of treatment effectiveness using bulk transcriptome sequencing.</p><p><strong>Results: </strong>Genes associated with cell proliferation, erythroid function, and amino acid transport were elevated in newly diagnosed AA. Conversely, genes linked to histones, thrombopoiesis, mitochondrial energy metabolism, and signaling pathways were significantly downregulated. Additionally, 60.6% of the differentially expressed genes were substantially restored following complete remission. Furthermore, through the examination of longitudinal samples, we identified recovery ascending genes that could serve as viable biomarkers for assessing treatment effectiveness in AA. Besides, we observed that higher expression levels of recovery ascending genes may predict superior long-term platelet counts recovery 6 months in advance in patients with partial response.</p><p><strong>Conclusion: </strong>The platelet transcriptome undergoes profound changes and can serve as a potential indicator for assessing treatment effectiveness and predicting long-term platelet counts recovery in AA.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemostatic derangements associated with cardiopulmonary bypass predict outcomes in pediatric patients undergoing corrective heart surgery.","authors":"Kevin Todd, Spencer J Hogue, James S Tweddell, James A Reagor, Eric Mullins, Mary G Block, Leah Rosenfeldt, Brenton Francisco, Sonata Jodele, Bal Krishan Sharma, Adam Lane, Craig Slusher, Mousa Kharnaf, David L S Morales, Joseph S Palumbo","doi":"10.1016/j.jtha.2024.10.029","DOIUrl":"10.1016/j.jtha.2024.10.029","url":null,"abstract":"<p><strong>Background: </strong>Understanding of the hemostatic and complement alterations associated with cardiopulmonary bypass (CPB) in pediatric patients and the impact of these alterations on outcome is limited.</p><p><strong>Objectives: </strong>The present study prospectively characterized these alterations and their association with postoperative outcomes in pediatric CPB.</p><p><strong>Methods: </strong>All patients aged <21 years undergoing CPB at the authors' institution between 2020 and 2021 who weighed >3 kg, were >36 weeks gestational age, and had no known prothrombotic or hemorrhagic disorders were eligible. Blood samples were analyzed for multiple hemostatic and complement biomarkers pre-, intra-, and 24 hours post-CPB. Biomarker levels were compared to clinical outcomes, including chest tube output (CTO).</p><p><strong>Results: </strong>Fifty consecutive patients were enrolled. CPB resulted in multiple significant alterations in hemostatic and complement components. Lower platelet counts (<80 × 10⁹ platelets/L) at CPB termination were associated with increased postoperative CTO (P = .003). Lower factor (F)VIII levels (<60 IU/dL) at the end of CPB were associated with a longer hospital stay (P < .001) and increased postoperative CTO (P < .001). Patients undergoing staged single ventricle reconstruction were more likely to have lower platelet counts at CPB termination (P = .009) and higher CTO postoperatively (P = .001) than patients undergoing other types of surgical repair. These differences were not due to different preoperative platelet counts, increased incidences of circulatory arrest, or longer CPB times.</p><p><strong>Conclusion: </strong>These data suggest that intraoperative alterations in hemostatic system components may predict postoperative outcomes in pediatric CPB. Further study is needed to determine if interventions targeting platelets or FVIII could improve outcomes in pediatric CPB.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining downstream effects of concizumab in hemophilia A with a mathematical modeling approach.","authors":"Kenji Miyazawa, Alan E Mast, Adam R Wufsus, Michael Dockal, Marianne Kjalke, Karin Leiderman","doi":"10.1016/j.jtha.2024.10.028","DOIUrl":"10.1016/j.jtha.2024.10.028","url":null,"abstract":"<p><strong>Background: </strong>Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits factor (F)Xa, the TF-FVIIa-FXa complex, and early forms of the prothrombinase complex. Concizumab is a monoclonal antibody that blocks FXa inhibition by TFPI and reduces bleeding in hemophilia.</p><p><strong>Objectives: </strong>To examine how concizumab impacts various reactions of TFPI to restore thrombin generation in hemophilia A using mathematical models.</p><p><strong>Methods: </strong>A compartment model was used to estimate plasma concentrations of free concizumab and its complexes with TFPIα and TFPIβ. Concizumab was integrated into a flow-mediated mathematical model of coagulation, and a small injury was simulated under hemophilia A conditions. Simulations were then analyzed to determine how concizumab's blockade of TFPI anticoagulant activities, specifically the inhibition of FXa in plasma and on platelets, inhibition of TF:FVIIa at the subendothelium, and prior sequestration of plasma TFPIα to the endothelium via TFPIβ, altered thrombin generation.</p><p><strong>Results: </strong>Concizumab improved simulated thrombin generation in hemophilia A by simultaneously altering all 3 mechanisms of the TFPI anticoagulant blockade examined. Concizumab sequestered ∼75% of plasma TFPIα through the formation of ternary TFPIα-concizumab-TFPIβ-complexes. For all TF levels, reducing the TFPIα plasma concentration had the largest impact on the lag time, followed by blocking TFPIα inhibition of TF:FVIIa:FXa and subsequently by blocking TFPIα inhibition of FXa in plasma and on the platelet surface.</p><p><strong>Conclusion: </strong>The effectiveness of concizumab is mediated through the blockade of TFPI anticoagulant activities in plasma and on multiple physiological surfaces. An important and previously unrecognized function of concizumab was the sequestration of plasma TFPIα to the endothelium.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired hemophilia A: a narrative review and management approach in the emicizumab era.","authors":"Patrick Ellsworth, Sheh-Li Chen, Lee Ann Jones, Alice D Ma, Nigel S Key","doi":"10.1016/j.jtha.2024.09.040","DOIUrl":"10.1016/j.jtha.2024.09.040","url":null,"abstract":"<p><p>Acquired hemophilia A (AHA) is a rare bleeding disorder caused by inhibitory autoantibodies to factor (F)VIII. The goals of treatment are 2-fold, namely immunosuppressive therapy to eradicate the inhibitor and hemostatic management to control bleeding. Emicizumab, a bispecific antibody that acts as a FVIIIa-mimetic, has seen growing use in AHA following its approval for congenital hemophilia A. This review provides an overview of the epidemiology, pathophysiology, diagnosis, and treatment of AHA. Registry, trial, and case series data are assimilated and summarized with an emphasis on a standardized approach that integrates the use of emicizumab. With recent registry data suggesting the need to focus on immunosuppression-related mortality in AHA, we provide treatment recommendations in an algorithmic format that have become the standard of care at our institution. These recommendations are intended to minimize hemostatic product usage and potential toxicity related to immunosuppressive therapy while reducing morbidity and rehospitalization rates for bleeding. The proposed treatment algorithm, which includes key interventions by phase of therapy, can be readily implemented at centers that have rapid access to plasma FVIII activity using a one-stage assay. A case is presented to illustrate the proposed diagnostic and management considerations.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deconstructing fibrin(ogen) structure.","authors":"Rebecca A Risman, Mehmet Sen, Valerie Tutwiler, Nathan E Hudson","doi":"10.1016/j.jtha.2024.10.024","DOIUrl":"10.1016/j.jtha.2024.10.024","url":null,"abstract":"<p><p>Fibrinogen and its insoluble degradation product fibrin are pivotal plasma proteins that play important roles in blood coagulation, wound healing, and immune responses. This review highlights research from the last 24 months connecting our progressing view of fibrin(ogen)'s structure, and in particular its conformational flexibility and posttranslational modifications, to its (patho)physiologic roles, molecular interactions, mechanical properties, use as a biomaterial, and potential as a therapeutic target. Recent work suggests that fibrinogen structure is highly dynamic, sampling multiple conformations, which may explain its myriad physiologic functions and the presence of cryptic binding sites. Investigations into fibrin clot structure elucidated the impact of posttranslational modifications, therapeutic interventions, and pathologic conditions on fibrin network morphology, offering insights into thrombus formation and embolization. Studies exploring the mechanical properties of fibrin reveal its response to blood flow and platelet-driven contraction, offering implications for clot stability and embolization risk. Moreover, advancements in tissue engineering leverage fibrin's biocompatibility and customizable properties for diverse applications, from wound healing to tissue regeneration and biomaterial interactions. These findings underscore the structural origins of fibrin(ogen)'s multifaceted roles and its potential as a target for therapeutic interventions.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}