Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Joint health status in patients with moderate hemophilia A: a cross-sectional multi-center study","authors":"Ilenia Calcaterra ,&nbsp;Federico Picasso ,&nbsp;Federica Valeri ,&nbsp;Erminia Baldacci ,&nbsp;Mariasanta Napolitano ,&nbsp;Cornelia Guerrino ,&nbsp;Ezio Zanon ,&nbsp;Cristina Santoro ,&nbsp;Sergio Siragusa ,&nbsp;Carlo Martinoli ,&nbsp;Matteo Nicola Dario Di Minno","doi":"10.1016/j.rpth.2025.102737","DOIUrl":"10.1016/j.rpth.2025.102737","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of arthropathy in patients with moderate hemophilia A (mHA) is highly variable. People with mHA are often under-treated, and this may lead to joint damage and worsen quality of life. The aim of the present study was to evaluate joint status in mHA by means of point-of-care ultrasound (PoC-US) and clinical examination.</div></div><div><h3>Methods</h3><div>Consecutive mHA patients receiving on-demand replacement treatment underwent a clinical examination of joint status according to HJHS protocol. On the same day, all patients underwent a PoC-US assessment according to the HEAD-US protocol.</div></div><div><h3>Results</h3><div>A total of 51 subjects were included. The median HJHS score was 2.0(IQR:0-3.0). A 0-1 HJHS score was found in 23 mHA patients (45.1%), between 2 and 3 in 17 (33.3%) and &gt;3 in 11 (21.6%). The median HEAD-US score was 2.0(IQR:1-7) and a statistically significant correlation between HJHS and HEAD-US was found (rho=0.732, p&lt;0.001). Osteochondral damage was found in 21.6% patients, hypertrophic synovium (HS) was found in 29.4%. Among those reporting a 0-1 HJHS score, 13.0% showed HS. The analysis at joint level showed that the most commonly affected joint was the ankle, both for osteochondral damage and for the presence of hypertrophic synovium.</div></div><div><h3>Conclusion</h3><div>Our study suggests that the prevalence of arthropathy changes in patients with mHA receiving on-demand treatment is not negligible and that PoC-US is able to detect osteochondral damage as well as HS in this clinical setting. A more extensive screening of the joint status could be useful to tailor treatment and improve outcome in mHA.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102737"},"PeriodicalIF":3.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777615","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 utility of panel-based genetic sequencing for von Willebrand disease","authors":"Radha Ramanan ,&nbsp;Christine Van Laer ,&nbsp;Sarissa Baert ,&nbsp;Cyrielle Kint ,&nbsp;Chris Van Geet ,&nbsp;Quentin Van Thillo ,&nbsp;Peter Verhamme ,&nbsp;Thomas Vanassche ,&nbsp;James D. McFadyen ,&nbsp;Andrew C. Perkins ,&nbsp;Huyen A. Tran ,&nbsp;Veerle Labarque ,&nbsp;Kathleen Freson","doi":"10.1016/j.rpth.2025.102730","DOIUrl":"10.1016/j.rpth.2025.102730","url":null,"abstract":"<div><h3>Introduction</h3><div>Von Willebrand disease (VWD) is the most prevalent inherited bleeding disorder with a wide spectrum of causative variants. Next-generation sequencing (NGS) analyses the entire <em>VWF</em> gene and provides concomitant assessment of other genes allowing differentiation between genocopies.</div></div><div><h3>Methods</h3><div>We conducted a single-centre retrospective study of all patients with confirmed or suspected VWD who were screened with panel-based whole-exome sequencing (WES) for inherited bleeding disorders. Pre-sequencing diagnosis was performed using laboratory measures of VWF activity and quantity. Post-sequencing diagnosis was informed by variant curation in combination with laboratory measures. We measured clinically meaningful changes in the pre- vs post-genetic sequencing diagnosis and subtyping.</div></div><div><h3>Results</h3><div>The study included 108 patients. The population was predominantly composed of paediatric patients &lt; 18 years old (77/108, 71%) and females (66/108, 61%). The largest pre-sequencing subgroup was those with low VWF (n=61, 56%), followed by type 1 VWD (n=21, 19%) and type 2 not otherwise specified (NOS) (n=18, 17%). A clinically meaningful change in management occurred in 19% (20/108) of the study population. The largest effect was seen in the pre-sequencing type 2 group (67%, 16/24). In the type 2 group who could not be accurately subtyped into 2A/B/M/N prior to sequencing (type 2 NOS), 15/18 (83%) were able to be subtyped or given a different diagnosis post sequencing.</div></div><div><h3>Conclusion</h3><div>Panel-based sequencing for VWD in a well-selected cohort, particularly those with type 2 and type 3 VWD, was clinically relevant in differentiating genocopies, directing therapies and family planning. Sequencing in those with low VWF and type 1 VWD rarely changed management.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102730"},"PeriodicalIF":3.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777603","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":"Platelet response following dexamethasone in obese vs nonobese patients with primary, acute immune-mediated thrombocytopenia","authors":"Tyler Everhardt ,&nbsp;Kelley Julian ,&nbsp;Russell Benefield ,&nbsp;Aaron Wilson ,&nbsp;Nathan Wilson ,&nbsp;Charles J. Parker ,&nbsp;Anna Parks ,&nbsp;Jeffrey A. Gilreath","doi":"10.1016/j.rpth.2025.102844","DOIUrl":"10.1016/j.rpth.2025.102844","url":null,"abstract":"<div><h3>Background</h3><div>Immune thrombocytopenia (ITP) is a rare autoimmune disorder defined as a platelet count &lt;100,000/μL, where secondary causes of thrombocytopenia have been excluded. Glucocorticoids are firstline therapy for ITP; however, data and recommendations on the impact of body weight and repeat steroid courses remain limited.</div></div><div><h3>Objectives</h3><div>We aimed to evaluate if body weight altered the response rates to dexamethasone (DEX) in the treatment of ITP.</div></div><div><h3>Methods</h3><div>We conducted a retrospective review to evaluate the effects of body weight on response to DEX in ITP. Patients were compared based on body mass index, presentation of ITP (acute or chronic), and cause of ITP (primary or secondary). Initial response, complete response, and relapse rates were among the outcomes investigated among the primary acute ITP population.</div></div><div><h3>Results</h3><div>Overall, 117 patients with ITP were identified, 49 of whom had primary acute ITP. Of these, 28 were categorized as nonobese, while 21 were obese. Nonobese patients were more likely to experience an initial platelet response to DEX than obese patients (93% vs 71%; <em>P</em> = .04), with 68% of nonobese patients also demonstrating a complete response compared with 48% of obese patients. Among patients who did not respond after 1 course of DEX, only 2 patients received another course prior to the initiation of alternative therapies. This is the second study to show that obese patients with primary acute ITP have significantly lower initial response rates and lower complete response rates to DEX compared with nonobese patients and that repeat DEX courses may be underutilized across all body mass index subgroups.</div></div><div><h3>Conclusion</h3><div>This study further highlights the need for additional data and guidance on optimal glucocorticoid dosing, especially in patients with obesity.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 3","pages":"Article 102844"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854431","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":"An assessment of evidence to inform best practice for the communication of acute venous thromboembolism diagnosis: a scoping review","authors":"Samarth Mishra ,&nbsp;Frederikus A. Klok ,&nbsp;Grégoire Le Gal ,&nbsp;Kerstin de Wit ,&nbsp;Aviva Schwartz ,&nbsp;Dieuwke Luijten ,&nbsp;Parham Sadeghipour ,&nbsp;Julie Bayley ,&nbsp;Scott C. Woller","doi":"10.1016/j.rpth.2025.102835","DOIUrl":"10.1016/j.rpth.2025.102835","url":null,"abstract":"<div><h3>Background</h3><div>Physician communication with patients is a key aspect of excellent care. Scant evidence exists to inform best practice for physician communication in patients diagnosed with pulmonary embolism and deep vein thrombosis, collectively referred to as venous thromboembolism (VTE).</div></div><div><h3>Objectives</h3><div>The aim of this study was to summarize the existing literature on best practices for communication between healthcare providers and patients newly diagnosed with VTE.</div></div><div><h3>Methods</h3><div>We performed a scoping review to report existing literature on best practices for physician-patient communication and the diagnosis and management of acute VTE. Manuscripts on communication between healthcare professionals and patients presenting with acute VTE and acute vascular disease presentations that included atrial fibrillation and acute coronary syndrome were identified. Two authors independently reviewed studies for eligibility and a consensus determined article inclusion. The manuscripts were further categorized into 2 categories: best practices in communication and unmet needs in communication. Data aggregation was achieved by a modified thematic synthesis.</div></div><div><h3>Results</h3><div>Among 345 initial publications, 22 manuscripts met inclusion criteria, with 11 addressing VTE, 5 pulmonary embolism, 4 deep vein thrombosis, 1 atrial fibrillation, and 1 acute coronary syndrome. Eleven manuscripts addressed communication of VTE diagnosis, while 12 focused on communication of VTE treatment. Eleven manuscripts identified unmet communication needs, and 14 addressed best practices. Our review showed that good communication enhanced satisfaction, while suboptimal communication was associated with emotional, cognitive, behavioral, social, and health systems adverse effects.</div></div><div><h3>Conclusion</h3><div>Scant literature guides best practices for communicating VTE diagnosis and treatment. Further research is necessary to establish practices for improving communication with VTE patients.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 3","pages":"Article 102835"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842598","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":"Hematopoietic stem cell transplantation in a newborn suffering from severe combined immunodeficiency and severe hemophilia A: a case report and review of the literature","authors":"Sarah Schober ,&nbsp;Michaela Döring ,&nbsp;Peter Lang ,&nbsp;Johannes Schulte ,&nbsp;Martin Olivieri ,&nbsp;Vanya Icheva","doi":"10.1016/j.rpth.2025.102842","DOIUrl":"10.1016/j.rpth.2025.102842","url":null,"abstract":"<div><h3>Background</h3><div>Severe combined immunodeficiency (SCID) and severe hemophilia A are 2 rare and potentially life-threatening congenital diseases. The coincidence of these diseases has not been reported so far.</div></div><div><h3>Key Clinical Question</h3><div>We present the first case of a newborn with both diseases. SCID can be treated with hematopoietic stem cell transplantation (HSCT). However, how to successfully manage a newborn with severe hemophilia A during intensive HSCT treatment is the key clinical question of this case report.</div></div><div><h3>Clinical Approach</h3><div>Prophylactic factor (F)VIII substitution during HSCT was performed with an extended half-life FVIII product (efmoroctocog alfa). The platelet count was a major factor influencing the dosage of FVIII. No bleeding complications or FVIII inhibitors occurred during this individualized management.</div></div><div><h3>Conclusion</h3><div>This is the first case report of a newborn suffering from both SCID and severe hemophilia A. HSCT is feasible in this situation without bleeding complications if an individual substitution regimen with FVIII is applied.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 3","pages":"Article 102842"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870292","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":"Comparison of 2 thromboelastography methods using patient and control samples","authors":"Robert Frick ,&nbsp;Brittany Washburn ,&nbsp;Dennis Plocher ,&nbsp;Jonathan K. Zoller ,&nbsp;Jason Gillihan ,&nbsp;Michael Dombrowski ,&nbsp;Charles Eby ,&nbsp;Christopher W. Farnsworth","doi":"10.1016/j.rpth.2025.102843","DOIUrl":"10.1016/j.rpth.2025.102843","url":null,"abstract":"<div><h3>Background</h3><div>Viscoelastic testing at point-of-care is associated with reduced blood loss and blood product transfusions. The ROTEM (Werfen) sigma is a cartridge-based system that may facilitate point-of-care use, but limited studies exist comparing the sigma with the predicated ROTEM delta.</div></div><div><h3>Objectives</h3><div>We compared the performance of the ROTEM delta with that of the sigma.</div></div><div><h3>Methods</h3><div>Citrated blood was collected from 20 healthy donors and patients during liver transplants (<em>n</em> = 17), obstetrics (<em>n</em> = 15), cardiovascular (<em>n</em> = 9), and trauma surgeries (<em>n</em> = 10). A method comparison was performed using the delta as the predicate. Imprecision was assessed at 2 levels for each assay. Manufacturer reference intervals were verified using 20 healthy donors. An algorithm used for cardiovascular surgery with the delta was compared with the sigma.</div></div><div><h3>Results</h3><div>The coefficient of variation was &lt;10% for all assays/parameters except for the thromboelastometry with extrinsic activation (EXTEM) clotting time (10.3%) and EXTEM amplitude (A)5 (10.2%). Reference intervals for the delta and sigma were comparable to manufacturer claims. The Pearson r comparing the delta and sigma exceeded .85 for all parameters/assays except for thromboelastometry with cytochalasin D-mediated platelet inhibition (FIBTEM) A10 (.77; 95% CI, .66-.86), FIBTEM A20 (.78; 95% CI, .65-.87), and thromboelastometry with heparinase clotting time (.77; 95% CI, .61-.87). No difference was observed in extrapolated thresholds from the delta-guided algorithm. However, extrapolated sigma A5 parameters for EXTEM were 5 mm lower, and for FIBTEM were 1 mm lower than delta A10 parameters.</div></div><div><h3>Conclusion</h3><div>The ROTEM delta and sigma devices had comparable performance. A negative bias was observed in the FIBTEM assay with lower extrapolated clinical decision points for a delta-guided treatment algorithm for the FIBTEM and EXTEM A5.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 3","pages":"Article 102843"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874512","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":"Plasma proteomics in patients with von Willebrand disease and hemophilia A highlights von Willebrand factor as main determinant of response to desmopressin treatment","authors":"Jessica del Castillo Alferez ,&nbsp;Eva R. Smit ,&nbsp;Alexander B. Meijer ,&nbsp;Karin Fijnvandraat ,&nbsp;Marieke J.H.A. Kruip ,&nbsp;Tirsa T. van Duijl ,&nbsp;Maartje van den Biggelaar","doi":"10.1016/j.rpth.2025.102738","DOIUrl":"10.1016/j.rpth.2025.102738","url":null,"abstract":"<div><h3>Background</h3><div>Desmopressin, 1-deamino-8-D-arginin vasopressin (DDAVP), is a treatment option for people with von Willebrand disease (VWD) and hemophilia A (HA) with a large interindividual variation in response. DDAVP elicits the release of von Willebrand Factor (VWF) from endothelial cells, thereby increasing the levels of circulating VWF and coagulation factor (F)VIII. However, we currently lack detailed insight on additional systemic effects of DDAVP administration on plasma protein levels.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate plasma proteomic profiles associated with DDAVP administration.</div></div><div><h3>Methods</h3><div>Longitudinal plasma samples of 13 patients with VWD and 9 people with mild HA up to 24 hours after DDAVP infusion were analyzed using mass spectrometry–based proteomics.</div></div><div><h3>Results</h3><div>Among 408 proteins quantified in plasma, only VWF and VWF propeptide (pp) increased significantly at 1 and 2 hours after DDAVP infusion in people with HA and VWD, respectively. VWF antigen levels were in agreement with mass spectrometry–based VWF intensity levels (<em>ρ</em> = 0.89). A slower clearance was observed for VWF compared with that for VWFpp, accompanied with higher interindividual variation. In 4 people with HA, C-reactive protein levels increased 24 hours after DDAVP infusion, which correlated with serum amyloid A1/A2 levels.</div></div><div><h3>Conclusion</h3><div>This study showed the selective increase of VWF and VWFpp 1 to 2 hours after DDAVP infusion and highlighted the interindividual variance in VWF clearance. Additionally, a delayed acute-phase response in a subgroup of patients suggested the potential role of inflammatory mechanisms contributing to heterogeneity of response.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 3","pages":"Article 102738"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834089","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":"Changes in body mass index following venous thromboembolism in children: a prospective cohort study","authors":"Mary P. Dang ,&nbsp;Maria Hanna ,&nbsp;Zhuo Tina Yang ,&nbsp;Kendra Malone ,&nbsp;Elliot S. Rinzler ,&nbsp;Song Zhang ,&nbsp;Ayesha Zia","doi":"10.1016/j.rpth.2025.102728","DOIUrl":"10.1016/j.rpth.2025.102728","url":null,"abstract":"<div><h3>Background</h3><div>We hypothesized that acute pediatric venous thromboembolism (VTE) is associated with an increase in body mass index (BMI) over time. We posited that if children gain weight following VTE, targeted interventions may be advised clinically or tested in future studies.</div></div><div><h3>Objectives</h3><div>The objectives of our study were to investigate BMI changes from VTE diagnosis to 3 and 6 months after diagnosis, identify predictors, and calculate the prevalence of overweight and obesity.</div></div><div><h3>Methods</h3><div>: In this prospective cohort study, we followed 63 participants (mean age, 12.8 years [SD, 5]) for 6 months following first episode of acute VTE. We chose percentage of BMI₉₅ (%-of-BMI₉₅) instead of absolute BMI as a measure of weight to standardize across sex and age and used change in %-of-BMI₉₅ as a measure of weight change. Δ%-of-BMI₉₅ was the primary outcome measure documenting change over time, categorized as increased if Δ%-of-BMI₉₅ was &gt;0, unchanged if Δ%-of-BMI₉₅ was 0, and decreased if Δ%-of-BMI₉₅ was &lt;0. To assess BMI changes, we created a prespecified subgroup of participants who required intensive care unit (ICU) vs those who did not.</div></div><div><h3>Results</h3><div>Sixty-two percent of participants were overweight/obese at diagnosis. Mean %-of-BMI₉₅ was 102.5% (95% CI, 95-109). The Δ%-of-BMI₉₅ at 3 and 6 months after diagnosis was, 1.5 (95% CI, −0.8 to 3.6) and 2.2 (95% CI, −0.6 to 5.2), respectively. We identified 3 predictors of weight change: non-ICU stay and longer length of stay predicted weight gain, whereas a higher %-of-BMI₉₅ at diagnosis in the ICU cohort correlated with decreased BMI.</div></div><div><h3>Conclusion</h3><div>BMI increases following pediatric VTE except those in the ICU. Weight-based counseling and lifestyle changes represent potential targeted interventions after VTE.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 3","pages":"Article 102728"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874513","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":"Risk factors and prognosis of symptomatic postpartum ovarian vein thrombosis in 2 French prospective cohort studies","authors":"Eloïse Laouenan ,&nbsp;Claire de Moreuil ,&nbsp;Sara Robin ,&nbsp;Karine Morcel ,&nbsp;François Anouilh ,&nbsp;Cécile Tromeur ,&nbsp;Francis Couturaud ,&nbsp;Emmanuelle Le Moigne","doi":"10.1016/j.rpth.2025.102849","DOIUrl":"10.1016/j.rpth.2025.102849","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 3","pages":"Article 102849"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879141","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":"Thiol isomerase ERp18 enhances platelet activation and arterial thrombosis","authors":"Chao He ,&nbsp;Aizhen Yang ,&nbsp;Keyu Lv ,&nbsp;Yuxin Zhang ,&nbsp;Zhenzhen Zhao ,&nbsp;Yi Lu ,&nbsp;Chao Fang ,&nbsp;Yue Han ,&nbsp;Depei Wu ,&nbsp;Miao Jiang ,&nbsp;Jingyu Zhang ,&nbsp;Yi Wu","doi":"10.1016/j.rpth.2025.102706","DOIUrl":"10.1016/j.rpth.2025.102706","url":null,"abstract":"<div><h3>Background</h3><div>Thiol isomerases regulate the thiol-disulfide exchange of functional proteins in cells. Using genetically modified mouse models and inhibitors, we and others demonstrated that 7 thiol isomerases (ERp57, protein diisulfide isomerase, ERp72, ERp46, ERp5, TMX4, and TMX1) participate in thrombosis. There are 21 thiol isomerases in mammals, but whether other enzymes of this family also contribute to thrombosis remains unknown.</div></div><div><h3>Objectives</h3><div>Investigate whether and how ERp18 participates in arterial thrombosis.</div></div><div><h3>Methods</h3><div>ERp18 knockout mice and arterial thrombosis models were used to determine the role of ERp18 in thrombosis. Platelets from ERp18 knockout mice were used to detect aggregation, activation, spreading, and clot retraction. Finally, flow cytometry and immunoprecipitation were used to detect the binding between ERp18 and α_IIbβ₃.</div></div><div><h3>Results</h3><div>The mice lacking ERp18 exhibited a prolonged tail bleeding time and decreased platelet thrombus formation in FeCl₃-induced carotid arterial injury and laser-induced cremaster artery injury models. ERp18 deficiency inhibited platelet aggregation, adenosine triphosphate release, integrin α_IIbβ₃ activation, P-selectin expression, platelet adhesion, as well as clot retraction. Flow cytometry and coimmunoprecipitation analyses revealed that ERp18 binds to the platelet surface via interaction with integrin α_IIbβ₃. Moreover, the ERp18 protein promoted the binding of integrin α_IIbβ₃ to fibrinogen and platelet aggregation. Furthermore, the recombinant ERp18 protein exhibited reductase activity and cleaved integrin α_IIbβ₃ disulfides.</div></div><div><h3>Conclusion</h3><div>ERp18 participates in platelet activation and thrombosis. Its function is, at least in part, through the regulation of integrin α_IIbβ₃ function. This finding expands our understanding of the role of thiol isomerases in the redox regulation of thrombosis and platelet function.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102706"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683442","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}