Thrombosis and haemostasis最新文献_第8页

Generation of a Severe Hemophilia A Humanized Mouse Model Capable of Inducing an Anti-FVIII Immune Response. 能够诱导抗fviii免疫应答的严重血友病人源化小鼠模型的产生

IF 5 2区医学

Thrombosis and haemostasis Pub Date : 2025-05-01 Epub Date: 2025-04-29 DOI: 10.1055/a-2518-7157

Akihisa Oda, Shoko Furukawa, Masahiro Kitabatake, Noriko Ouji-Sageshima, Toshihiro Ito, Riichi Takahashi, Takeshi Kawamura, Yuto Nakajima, Naruto Shimonishi, Kenichi Ogiwara, Midori Shima, Keiji Nogami

{"title":"Generation of a Severe Hemophilia A Humanized Mouse Model Capable of Inducing an Anti-FVIII Immune Response.","authors":"Akihisa Oda, Shoko Furukawa, Masahiro Kitabatake, Noriko Ouji-Sageshima, Toshihiro Ito, Riichi Takahashi, Takeshi Kawamura, Yuto Nakajima, Naruto Shimonishi, Kenichi Ogiwara, Midori Shima, Keiji Nogami","doi":"10.1055/a-2518-7157","DOIUrl":"https://doi.org/10.1055/a-2518-7157","url":null,"abstract":"Factor VIII (FVIII) replacement therapy induces anti-FVIII neutralizing antibodies in approximately 30% of patients with severe hemophilia A (HA). Owing to the lack of experimental systems that allow for the study of human anti-FVIII immune responses, the mechanisms underlying replacement therapy-induced anti-FVIII antibodies in HA patients remain largely unknown. Therefore, experimental systems that enable the study of human anti-FVIII immune responses are needed.We generated severe immunodeficient NOD-scid IL-2Rnull; FVIIInull mice (NOG HA) that can serve as hosts for human cord blood (hCB) transplantation and established a HA mouse with a humanized immune system to induce the anti-FVIII responses in human immune cells in vivo.The proportions of immune cell subsets (CD8+ T cells, CD4+ T cells, CD19+ B cells, CD33+ macrophages, and CD56+ natural killer (NK) cells) in the bone marrow, spleen, and peripheral blood were similar between NOG HA and NOG mice 4 months after hCB transplantation. The hCB-engrafted NOG HA mice retained HA severity. To activate the anti-FVIII immune response in hCB-engrafted NOG HA mice, we administered recombinant (r)FVIII plus lipopolysaccharide (LPS) once a week for 3 months. We detected both anti-FVIII IgM and IgG in the plasma of hCB-engrafted NOG HA mice after treatment with 12 doses of rFVIII and LPS. Taken together, our humanized mice with HA maintained a severe phenotype and generated human anti-FVIII IgG antibodies in vivo, thus representing a valuable model for studying human anti-FVIII immune responses.","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":"125 5","pages":"435-446"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064730","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}

引用次数: 0

Elevated Protein S Provides Evidence against Hypoxia-Induced Hypercoagulation in Tibetan Highlanders with PHD2D4E;C127S Polymorphisms. 蛋白S升高为青藏高原PHD2D4E；C127S多态性患者抗缺氧诱导的高凝提供了证据

IF 5 2区医学

Thrombosis and haemostasis Pub Date : 2025-05-01 DOI: 10.1055/a-2580-0107

Nishith M Shrimali, Riya Ghosh, Kanchan Bhardwaj, Chorol Tsewang, Tashi Thinlas, Parvaiz Koul, Josef T Prchal, Prasenjit Guchhait

引用次数: 0

Harnessing Risk Assessment for Thrombosis and Bleeding to Optimize Anticoagulation Strategy in Nonvalvular Atrial Fibrillation. 利用血栓和出血风险评估优化非瓣膜性心房颤动的抗凝策略。

IF 5 2区医学

Thrombosis and haemostasis Pub Date : 2025-05-01 Epub Date: 2024-08-13 DOI: 10.1055/a-2385-1452

Yue Zhao, Li-Ya Cao, Ying-Xin Zhao, Di Zhao, Yi-Fan Huang, Fei Wang, Qian Wang

{"title":"Harnessing Risk Assessment for Thrombosis and Bleeding to Optimize Anticoagulation Strategy in Nonvalvular Atrial Fibrillation.","authors":"Yue Zhao, Li-Ya Cao, Ying-Xin Zhao, Di Zhao, Yi-Fan Huang, Fei Wang, Qian Wang","doi":"10.1055/a-2385-1452","DOIUrl":"10.1055/a-2385-1452","url":null,"abstract":"Oral anticoagulation (OAC) following catheter ablation (CA) of nonvalvular atrial fibrillation (NVAF) is essential for the prevention of thrombosis events. Inappropriate application of OACs does not benefit stroke prevention but may be associated with a higher risk of bleeding. Therefore, this study aims to develop clinical data-driven machine learning (ML) methods to predict the risk of thrombosis and bleeding to establish more precise anticoagulation strategies for patients with NVAF.Patients with NVAF who underwent CA therapy were enrolled from Southwest Hospital from 2015 to 2023. This study compared eight ML algorithms to evaluate the predictive power for both thrombosis and bleeding. Model interpretations were recognized by feature importance and SHapley Additive exPlanations methods. With potential essential risk factors, simplified ML models were proposed to improve the feasibility of the tool.A total of 1,055 participants were recruited, including 105 patients with thrombosis and 252 patients with bleeding. The models based on XGBoost achieved the best performance with accuracies of 0.740 and 0.781 for thrombosis and bleeding, respectively. Age, BNP, and the duration of heparin are closely related to the high risk of thrombosis, whereas the anticoagulation strategy, BNP, and lipids play a crucial role in the occurrence of bleeding. The optimized models enrolling crucial risk factors, RF-T for thrombosis and Xw-B for bleeding, achieved the best recalls of 0.774 and 0.780, respectively.The optimized models will have a great application potential in predicting thrombosis and bleeding among patients with NVAF and will form the basis for future score scales.","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"492-504"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Rise of the Machines: Using Machine Learning to Assess Thrombosis and Bleeding Risks, and Optimizing Anticoagulation Strategies. 机器的崛起：使用机器学习来评估血栓和出血风险，并优化抗凝策略。

IF 5 2区医学

Thrombosis and haemostasis Pub Date : 2025-05-01 Epub Date: 2024-11-29 DOI: 10.1055/a-2460-2894

Sandra Ortega-Martorell, Evi van Kempen, Eric Jouvent, Anil M Tuladhar

引用次数: 0

Inhibitor Formation in the Era of Novel Haemophilia Treatment-A Humanized Mouse Model to Answer Our Questions? 新型血友病治疗时代抑制剂形成——人源化小鼠模型回答我们的问题？

IF 5 2区医学

Thrombosis and haemostasis Pub Date : 2025-05-01 Epub Date: 2025-03-06 DOI: 10.1055/a-2551-8561

Lize F D van Vulpen, Simon C Mastbergen

引用次数: 0

Final Analysis Results from the AGEHA Study: Emicizumab Prophylaxis for Acquired Hemophilia A with or without Immunosuppressive Therapy. AGEHA 研究的最终分析结果：使用或不使用免疫抑制剂治疗获得性甲型血友病的埃米珠单抗预防疗法。

IF 5 2区医学

Thrombosis and haemostasis Pub Date : 2025-05-01 Epub Date: 2024-08-12 DOI: 10.1055/a-2384-3585

Midori Shima, Nobuaki Suzuki, Hidekazu Nishikii, Kagehiro Amano, Yoshiyuki Ogawa, Ryota Kobayashi, Ryoto Ozaki, Koichiro Yoneyama, Narumi Mizuno, Emiko Sakaida, Makoto Saito, Takashi Okamura, Toshihiro Ito, Norimichi Hattori, Satoshi Higasa, Yoshinobu Seki, Keiji Nogami

{"title":"Final Analysis Results from the AGEHA Study: Emicizumab Prophylaxis for Acquired Hemophilia A with or without Immunosuppressive Therapy.","authors":"Midori Shima, Nobuaki Suzuki, Hidekazu Nishikii, Kagehiro Amano, Yoshiyuki Ogawa, Ryota Kobayashi, Ryoto Ozaki, Koichiro Yoneyama, Narumi Mizuno, Emiko Sakaida, Makoto Saito, Takashi Okamura, Toshihiro Ito, Norimichi Hattori, Satoshi Higasa, Yoshinobu Seki, Keiji Nogami","doi":"10.1055/a-2384-3585","DOIUrl":"10.1055/a-2384-3585","url":null,"abstract":"Primary analysis of the phase III AGEHA study suggested a favorable benefit-risk profile for emicizumab prophylaxis in patients with acquired hemophilia A (PwAHA); however, only patients undergoing immunosuppressive therapy (IST; Cohort 1) were included.To present final analysis results of AGEHA, including data on IST-ineligible patients (Cohort 2) and on long-term prophylaxis with emicizumab.For patients in both Cohorts 1 and 2, emicizumab was administered subcutaneously at 6 mg/kg on Day 1, 3 mg/kg on Day 2, and 1.5 mg/kg once weekly from Day 8 onward.Twelve patients (Cohort 1) and two patients (Cohort 2) were enrolled. Duration of emicizumab treatment was 8 to 639 days (median: 44.5 days) in Cohort 1 and 64 and 450 days in Cohort 2. In both cohorts, no major bleeds were observed after initial emicizumab administration. Six patients started their first rehabilitation sessions during emicizumab treatment and no rehabilitation-related bleeds occurred. Twenty-three surgeries were performed under emicizumab prophylaxis and there were no bleeds related to surgeries. Although asymptomatic deep vein thrombosis was reported in one patient in the primary analysis, no other thrombotic events occurred thereafter. Two patients developed anti-emicizumab antibodies, one of whom showed accelerated emicizumab clearance. Tailored IST approaches (delayed initiation, no use, or reduced dose) were successfully executed in three patients undergoing emicizumab prophylaxis.These results suggest that emicizumab prophylaxis has a favorable benefit-risk profile in PwAHA regardless of eligibility for IST.","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"449-459"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Handheld Point-of-Care Devices for Snakebite Coagulopathy: A Scoping Review. 治疗蛇伤凝血病的手持式护理点设备：范围界定综述。

IF 5 2区医学

Thrombosis and haemostasis Pub Date : 2025-05-01 Epub Date: 2024-08-30 DOI: 10.1055/a-2407-1400

Michael Abouyannis, Amy E Marriott, Emma Stars, Dianne P Kitchen, Steve Kitchen, Tim A L Woods, Benno Kreuels, John H Amuasi, Wuelton M Monteiro, Ymkje Stienstra, Subramanian Senthilkumaran, Geoff K Isbister, David G Lalloo, Stuart Ainsworth, Nicholas R Casewell

{"title":"Handheld Point-of-Care Devices for Snakebite Coagulopathy: A Scoping Review.","authors":"Michael Abouyannis, Amy E Marriott, Emma Stars, Dianne P Kitchen, Steve Kitchen, Tim A L Woods, Benno Kreuels, John H Amuasi, Wuelton M Monteiro, Ymkje Stienstra, Subramanian Senthilkumaran, Geoff K Isbister, David G Lalloo, Stuart Ainsworth, Nicholas R Casewell","doi":"10.1055/a-2407-1400","DOIUrl":"10.1055/a-2407-1400","url":null,"abstract":"Venom-induced consumption coagulopathy (VICC) is a common complication of snakebite that is associated with hypofibrinogenemia, bleeding, disability, and death. In remote tropical settings, where most snakebites occur, the 20-minute whole blood clotting test is used to diagnose VICC. Point-of-care (POC) coagulation devices could provide an accessible means of detecting VICC that is better standardized, quantifiable, and more accurate. In this scoping review, the mechanistic reasons that previously studied POC devices have failed in VICC are considered, and evidence-based recommendations are made to prioritize certain devices for clinical validation studies. Four small studies have evaluated a POC international normalized ratio (INR) device in patients with Australian Elapid, Daboia russelii, and Echis carinatus envenoming. The devices assessed in these studies either relied on a thrombin substrate endpoint, which is known to underestimate INR in patients with hypofibrinogenemia, have been recalled due to poor accuracy, or have since been discontinued. Sixteen commercially available POC devices for measuring INR, activated clotting time, activated partial thromboplastin time, fibrinogen, D-dimer, and fibrin(ogen) degradation products have been reviewed. POC INR devices that detect fibrin clot formation, as well as a novel POC device that quantifies fibrinogen were identified, which show promise for use in patients with VICC. These devices could support more accurate allocation of antivenom, reduce the time to antivenom administration, and provide improved clinical trial outcome measurement instruments. There is an urgent need for these promising POC coagulation devices to be validated in prospective clinical snakebite studies.","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"405-420"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reversible Thrombocytopenia of Functional Platelets after Nose-Horned Viper Envenomation is Induced by a Snaclec. 鼻角蝰中毒后功能性血小板可逆性减少是由 Snaclec 诱导的。

IF 5 2区医学

Thrombosis and haemostasis Pub Date : 2025-05-01 Epub Date: 2024-09-03 DOI: 10.1055/a-2408-9375

Mojca Dobaja Borak, Adrijana Leonardi, Kity Požek, Katarina Reberšek, Helena Podgornik, Aljaž Pirnat, Alenka Trampuš Bakija, Simona Kranjc Brezar, Tomaž Trobec, Monika C Žužek, Robert Frangež, Miran Brvar, Igor Križaj

{"title":"Reversible Thrombocytopenia of Functional Platelets after Nose-Horned Viper Envenomation is Induced by a Snaclec.","authors":"Mojca Dobaja Borak, Adrijana Leonardi, Kity Požek, Katarina Reberšek, Helena Podgornik, Aljaž Pirnat, Alenka Trampuš Bakija, Simona Kranjc Brezar, Tomaž Trobec, Monika C Žužek, Robert Frangež, Miran Brvar, Igor Križaj","doi":"10.1055/a-2408-9375","DOIUrl":"10.1055/a-2408-9375","url":null,"abstract":"Profound and transient thrombocytopenia of functional platelets without bleeding was observed in patients envenomed by Vipera a. ammodytes (Vaa). This condition was rapidly reversed by administration of F(ab)2 fragments of immunoglobulin G targeting the whole venom, leaving platelets fully functional. To investigate the potential role of snake venom C-type lectin-like proteins (snaclecs) in this process, Vaa-snaclecs were isolated from the crude venom using different liquid chromatographies. The purity of the isolated proteins was confirmed by Edman sequencing and mass spectrometry. The antithrombotic effect was investigated by platelet agglutination and aggregation assays and blood coagulation tests. Using flow cytometry, the platelet activation and binding of Vaa-snaclecs to various platelet receptors was analyzed. Antithrombotic efficacy was tested in vivo using a mouse model of vascular injury. Two Vaa-snaclecs were purified from the venom. One of them, Vaa-snaclec-3/2, inhibited ristocetin-induced platelet agglutination. It is a covalent heterodimer of Vaa-snaclec-3 (α-subunit) and Vaa-snaclec-2 (β-subunit). Our results suggest that Vaa-snaclec-3/2 induces platelet agglutination and consequently thrombocytopenia by binding to the platelet receptor glycoprotein Ib. Essentially, no platelet activation was observed in this process. In vivo, Vaa-snaclec-3/2 was able to protect the mouse from ferric chloride-induced carotid artery thrombosis, revealing its applicative potential in interventional angiology and cardiology.","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"484-491"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Venous Thromboembolism in Patients with Glioblastoma: Molecular Mechanisms and Clinical Implications. 胶质母细胞瘤患者的静脉血栓栓塞症：分子机制和临床意义。

IF 5 2区医学

Thrombosis and haemostasis Pub Date : 2025-05-01 Epub Date: 2024-08-21 DOI: 10.1055/s-0044-1789592

Maaike Y Kapteijn, Nina Bakker, Johan A F Koekkoek, Henri H Versteeg, Jeroen T Buijs

{"title":"Venous Thromboembolism in Patients with Glioblastoma: Molecular Mechanisms and Clinical Implications.","authors":"Maaike Y Kapteijn, Nina Bakker, Johan A F Koekkoek, Henri H Versteeg, Jeroen T Buijs","doi":"10.1055/s-0044-1789592","DOIUrl":"10.1055/s-0044-1789592","url":null,"abstract":"Patients with glioblastoma are among the cancer patients with the highest risk of developing venous thromboembolism (VTE). Long-term thromboprophylaxis is not generally prescribed because of the increased susceptibility of glioblastoma patients to intracranial hemorrhage. This review provides an overview of the current clinical standard for glioblastoma patients, as well as the molecular and genetic background which underlies the high incidence of VTE. The two main procoagulant proteins involved in glioblastoma-related VTE, podoplanin and tissue factor, are described, in addition to the genetic aberrations that can be linked to a hypercoagulable state in glioblastoma. Furthermore, possible novel biomarkers and future treatment strategies are discussed, along with the potential of sequencing approaches toward personalized risk prediction for VTE. A glioblastoma-specific VTE risk stratification model may help identifying those patients in which the increased risk of bleeding due to extended anticoagulation is outweighed by the decreased risk of VTE.","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"421-434"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Personalized Medicine, Public Health and Patient-Centred Aspects in the Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation (PRESTIGE-AF) Project. 房颤脑出血幸存者中风预防的个体化医学、公共卫生和以患者为中心（PRESTIGE-AF）项目

IF 5 2区医学

Thrombosis and haemostasis Pub Date : 2025-04-30 DOI: 10.1055/a-2576-7760

Kirsten H Harvey, Eleni Korompoki, Emily R Harvey, Cornelia Fießler, Uwe Malzahn, Klemens Hügen, Sabine Ullmann, Carolin Schuhmann, Gabriele Putz Todd, Joan Montaner, Anna Penalba, Daisy Guaman-Pilco, Igor Sibon, Stephanie Debette, Timothy D'Aoust, Morgane Lachaize, Christian Enzinger, Stefan Ropele, Simon Fandler-Höfler, Viktoria Ruecker, Kirsten Haas, Peter B Nielsen, Charles Wolfe, Yanzhong Wang, Hatem Wafa, Valeria Caso, Maria Giulia Mosconi, Gregory Y H Lip, Deirdre A Lane, Walter E Haefeli, Kathrin I Foerster, Viktoria S Wurmbach, Peter Ringleb, Peter U Heuschmann, Roland Veltkamp

引用次数: 0