Seminars in thrombosis and hemostasis最新文献_第2页

Plasma Kallikrein as a Forgotten Clotting Factor. 血浆 Kallikrein 是一种被遗忘的凝血因子。

IF 3.6 2区医学

Seminars in thrombosis and hemostasis Pub Date : 2024-10-01 Epub Date: 2023-04-18 DOI: 10.1055/s-0043-57034

Katherine J Kearney, Henri M H Spronk, Jonas Emsley, Nigel S Key, Helen Philippou

{"title":"Plasma Kallikrein as a Forgotten Clotting Factor.","authors":"Katherine J Kearney, Henri M H Spronk, Jonas Emsley, Nigel S Key, Helen Philippou","doi":"10.1055/s-0043-57034","DOIUrl":"10.1055/s-0043-57034","url":null,"abstract":"For decades, it was considered that plasma kallikrein's (PKa) sole function within the coagulation cascade is the activation of factor (F)XII. Until recently, the two key known activators of FIX within the coagulation cascade were activated FXI(a) and the tissue factor-FVII(a) complex. Simultaneously, and using independent experimental approaches, three groups identified a new branch of the coagulation cascade, whereby PKa can directly activate FIX. These key studies identified that (1) FIX or FIXa can bind with high affinity to either prekallikrein (PK) or PKa; (2) in human plasma, PKa can dose dependently trigger thrombin generation and clot formation independent of FXI; (3) in FXI knockout murine models treated with intrinsic pathway agonists, PKa activity results in increased formation of FIXa:AT complexes, indicating direct activation of FIX by PKa in vivo. These findings suggest that there is both a canonical (FXIa-dependent) and non-canonical (PKa-dependent) pathway of FIX activation. These three recent studies are described within this review, alongside historical data that hinted at the existence of this novel role of PKa as a coagulation clotting factor. The implications of direct PKa cleavage of FIX remain to be determined physiologically, pathophysiologically, and in the context of next-generation anticoagulants in development.","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000934","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

Hereditary Angioedema: The Clinical Picture of Excessive Contact Activation. 遗传性血管性水肿：过度接触性激活的临床表现。

IF 3.6 2区医学

Seminars in thrombosis and hemostasis Pub Date : 2024-10-01 Epub Date: 2022-11-23 DOI: 10.1055/s-0042-1758820

Remy S Petersen, Lauré M Fijen, Marcel Levi, Danny M Cohn

{"title":"Hereditary Angioedema: The Clinical Picture of Excessive Contact Activation.","authors":"Remy S Petersen, Lauré M Fijen, Marcel Levi, Danny M Cohn","doi":"10.1055/s-0042-1758820","DOIUrl":"10.1055/s-0042-1758820","url":null,"abstract":"Hereditary angioedema is a rare, genetic disorder characterized by painful, debilitating and potentially life-threatening angioedema attacks in subcutaneous and submucosal tissue. While usually unpredictable, attacks can be provoked by a variety of triggers including physical injury and certain medication and are often preceded by prodromal symptoms. Hereditary angioedema has a profound influence on the patients' lives. The fundamental cause of hereditary angioedema in almost all patients is a mutation in the SERPING1 gene leading to a deficiency in C1-inhibitor. Subsequently, the contact activation cascade and kallikrein-kinin pathway are insufficiently inhibited, resulting in excessive bradykinin production triggering vascular leakage. While C1-inhibitor is an important regulator of the intrinsic coagulation pathway, fibrinolytic system and complement cascade, patients do not have an increased risk of coagulopathy, autoimmune conditions or immunodeficiency disorders. Hereditary angioedema is diagnosed based on C1-inhibitor level and function. Genetic analysis is only required in rare cases where hereditary angioedema with normal C1-inhibitor is found. In recent years, new, highly specific therapies have greatly improved disease control and angioedema-related quality of life. This article reviews the clinical picture of hereditary angioedema, the underlying pathophysiology, diagnostic process and currently available as well as investigational therapeutic options.","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11407848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40507428","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 Next, Next-Generation of Sequencing, Promising to Boost Research and Clinical Practice. 下一代测序技术，有望促进研究和临床实践。

IF 3.6 2区医学

Seminars in thrombosis and hemostasis Pub Date : 2024-10-01 Epub Date: 2024-05-11 DOI: 10.1055/s-0044-1786756

Kishore R Kumar, Mark J Cowley, Ryan L Davis

引用次数: 0

Targeting the Contact Pathway of Coagulation for the Prevention and Management of Medical Device-Associated Thrombosis. 以凝血接触途径为目标，预防和处理医疗器械相关血栓。

IF 3.6 2区医学

Seminars in thrombosis and hemostasis Pub Date : 2024-10-01 Epub Date: 2023-04-12 DOI: 10.1055/s-0043-57011

Abhishek Goel, Harsha Tathireddy, Si-Han Wang, Helen H Vu, Cristina Puy, Monica T Hinds, David Zonies, Owen J T McCarty, Joseph J Shatzel

{"title":"Targeting the Contact Pathway of Coagulation for the Prevention and Management of Medical Device-Associated Thrombosis.","authors":"Abhishek Goel, Harsha Tathireddy, Si-Han Wang, Helen H Vu, Cristina Puy, Monica T Hinds, David Zonies, Owen J T McCarty, Joseph J Shatzel","doi":"10.1055/s-0043-57011","DOIUrl":"10.1055/s-0043-57011","url":null,"abstract":"Hemorrhage remains a major complication of anticoagulants, with bleeding leading to serious and even life-threatening outcomes in rare settings. Currently available anticoagulants target either multiple coagulation factors or specifically coagulation factor (F) Xa or thrombin; however, inhibiting these pathways universally impairs hemostasis. Bleeding complications are especially salient in the medically complex population who benefit from medical devices. Extracorporeal devices-such as extracorporeal membrane oxygenation, hemodialysis, and cardiac bypass-require anticoagulation for optimal use. Nonetheless, bleeding complications are common, and with certain devices, highly morbid. Likewise, pharmacologic prophylaxis to prevent thrombosis is not commonly used with many medical devices like central venous catheters due to high rates of bleeding. The contact pathway members FXI, FXII, and prekallikrein serve as a nexus, connecting biomaterial surface-mediated thrombin generation and inflammation, and may represent safe, druggable targets to improve medical device hemocompatibility and thrombogenicity. Recent in vivo and clinical data suggest that selectively targeting the contact pathway of coagulation through the inhibition of FXI and FXII can reduce the incidence of medical device-associated thrombotic events, and potentially systemic inflammation, without impairing hemostasis. In the following review, we will outline the current in vivo and clinical data encompassing the mechanism of action of drugs targeting the contact pathway. This new class of inhibitors has the potential to herald a new era of effective and low-risk anticoagulation for the management of patients requiring the use of medical devices.","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11069398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9295467","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

Substrates, Cofactors, and Cellular Targets of Coagulation Factor XIa. 凝血因子 XIa 的底物、辅因子和细胞靶标

IF 3.6 2区医学

Seminars in thrombosis and hemostasis Pub Date : 2024-10-01 Epub Date: 2023-03-20 DOI: 10.1055/s-0043-1764469

André L Lira, Tia C L Kohs, Samantha A Moellmer, Joseph J Shatzel, Owen J T McCarty, Cristina Puy

{"title":"Substrates, Cofactors, and Cellular Targets of Coagulation Factor XIa.","authors":"André L Lira, Tia C L Kohs, Samantha A Moellmer, Joseph J Shatzel, Owen J T McCarty, Cristina Puy","doi":"10.1055/s-0043-1764469","DOIUrl":"10.1055/s-0043-1764469","url":null,"abstract":"Coagulation factor XI (FXI) has increasingly been shown to play an integral role in several physiologic and pathological processes. FXI is among several zymogens within the blood coagulation cascade that are activated by proteolytic cleavage, with FXI converting to the active serine protease form (FXIa). The evolutionary origins of FXI trace back to duplication of the gene that transcribes plasma prekallikrein, a key factor in the plasma kallikrein-kinin system, before further genetic divergence led to FXI playing a unique role in blood coagulation. While FXIa is canonically known for activating the intrinsic pathway of coagulation by catalyzing the conversion of FIX into FIXa, it is promiscuous in nature and has been shown to contribute to thrombin generation independent of FIX. In addition to its role in the intrinsic pathway of coagulation, FXI also interacts with platelets, endothelial cells, and mediates the inflammatory response through activation of FXII and cleavage of high-molecular-weight kininogen to generate bradykinin. In this manuscript, we critically review the current body of knowledge surrounding how FXI navigates the interplay of hemostasis, inflammatory processes, and the immune response and highlight future avenues for research. As FXI continues to be clinically explored as a druggable therapeutic target, understanding how this coagulation factor fits into physiological and disease mechanisms becomes increasingly important.","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11069399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9342316","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 Role of Myeloid Cells in Thromboinflammatory Disease. 髓系细胞在血栓性炎症中的作用

IF 3.6 2区医学

Seminars in thrombosis and hemostasis Pub Date : 2024-10-01 Epub Date: 2024-03-28 DOI: 10.1055/s-0044-1782660

David Noone, Roger J S Preston, Aisling M Rehill

{"title":"The Role of Myeloid Cells in Thromboinflammatory Disease.","authors":"David Noone, Roger J S Preston, Aisling M Rehill","doi":"10.1055/s-0044-1782660","DOIUrl":"10.1055/s-0044-1782660","url":null,"abstract":"Inflammation contributes to the development of thrombosis, but the mechanistic basis for this association remains poorly understood. Innate immune responses and coagulation pathways are activated in parallel following infection or injury, and represent an important host defense mechanism to limit pathogen spread in the bloodstream. However, dysregulated proinflammatory activity is implicated in the progression of venous thromboembolism and arterial thrombosis. In this review, we focus on the role of myeloid cells in propagating thromboinflammation in acute inflammatory conditions, such as sepsis and coronavirus disease 2019 (COVID-19), and chronic inflammatory conditions, such as obesity, atherosclerosis, and inflammatory bowel disease. Myeloid cells are considered key drivers of thromboinflammation via upregulated tissue factor activity, formation of neutrophil extracellular traps (NETs), contact pathway activation, and aberrant coagulation factor-mediated protease-activated receptor (PAR) signaling. We discuss how strategies to target the intersection between myeloid cell-mediated inflammation and activation of blood coagulation represent an exciting new approach to combat immunothrombosis. Specifically, repurposed anti-inflammatory drugs, immunometabolic regulators, and NETosis inhibitors present opportunities that have the potential to dampen immunothrombotic activity without interfering with hemostasis. Such therapies could have far-reaching benefits for patient care across many thromboinflammatory conditions.","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319081","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

Vascular Pathogenesis in Acute and Long COVID: Current Insights and Therapeutic Outlook. 急性和长期 COVID 的血管发病机制：当前见解和治疗展望。

IF 3.6 2区医学

Seminars in thrombosis and hemostasis Pub Date : 2024-09-30 DOI: 10.1055/s-0044-1790603

Arneaux Kruger, David Joffe, Graham Lloyd-Jones, Muhammed Asad Khan, Špela Šalamon, Gert J Laubscher, David Putrino, Douglas B Kell, Etheresia Pretorius

{"title":"Vascular Pathogenesis in Acute and Long COVID: Current Insights and Therapeutic Outlook.","authors":"Arneaux Kruger, David Joffe, Graham Lloyd-Jones, Muhammed Asad Khan, Špela Šalamon, Gert J Laubscher, David Putrino, Douglas B Kell, Etheresia Pretorius","doi":"10.1055/s-0044-1790603","DOIUrl":"https://doi.org/10.1055/s-0044-1790603","url":null,"abstract":"Long coronavirus disease 2019 (COVID-19)-a postacute consequence of severe acute respiratory syndrome coronavirus 2 infection-manifests with a broad spectrum of relapsing and remitting or persistent symptoms as well as varied levels of organ damage, which may be asymptomatic or present as acute events such as heart attacks or strokes and recurrent infections, hinting at complex underlying pathogenic mechanisms. Central to these symptoms is vascular dysfunction rooted in thrombotic endothelialitis. We review the scientific evidence that widespread endothelial dysfunction (ED) leads to chronic symptomatology. We briefly examine the molecular pathways contributing to endothelial pathology and provide a detailed analysis of how these cellular processes underpin the clinical picture. Noninvasive diagnostic techniques, such as flow-mediated dilation and peripheral arterial tonometry, are evaluated for their utility in identifying ED. We then explore mechanistic, cellular-targeted therapeutic interventions for their potential in treating ED. Overall, we emphasize the critical role of cellular health in managing Long COVID and highlight the need for early intervention to prevent long-term vascular and cellular dysfunction.","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353072","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

Secondary Anticoagulation Use in Patients < 21 Years Old following Primary Anticoagulant Treatment for Provoked Venous Thromboembolism: Findings from the Kids-DOTT Trial. 小于 21 岁的患者因诱发静脉血栓栓塞而接受初级抗凝治疗后的二次抗凝治疗：Kids-DOTT 试验结果。

IF 3.6 2区医学

Seminars in thrombosis and hemostasis Pub Date : 2024-09-19 DOI: 10.1055/s-0044-1790572

Hope P Wilson, Maua Mosha, Alexandra Miller, Marisol Betensky, Ernest Amankwah, John Fargo, Courtney D Thornburg, Cristina Tarango, Suchitra Acharya, Christoph Male, Shalu Narang, Sam Schulman, Neil A Goldenberg

引用次数: 0

Inherited Disorders of the Fibrinolytic Pathway: Pathogenic Phenotypes and Diagnostic Considerations of Extremely Rare Disorders. 纤维蛋白溶解途径的遗传性疾病：极罕见疾病的致病表型和诊断注意事项》（Pathogenic Phenotypes and Diagnostic Considerations of Extremely Rare Disorders）。

IF 3.6 2区医学

Seminars in thrombosis and hemostasis Pub Date : 2024-09-19 DOI: 10.1055/s-0044-1789596

Maha Al-Ghafry, Mouhamed Yazan Abou-Ismail, Suchitra S Acharya

{"title":"Inherited Disorders of the Fibrinolytic Pathway: Pathogenic Phenotypes and Diagnostic Considerations of Extremely Rare Disorders.","authors":"Maha Al-Ghafry, Mouhamed Yazan Abou-Ismail, Suchitra S Acharya","doi":"10.1055/s-0044-1789596","DOIUrl":"https://doi.org/10.1055/s-0044-1789596","url":null,"abstract":"Fibrinolysis is initiated by the activation of plasminogen to plasmin via tissue-plasminogen activator (tPA) and urokinase-plasminogen activator (uPA); plasmin then converts fibrin to fibrin degradation products (FDPs). The antifibrinolytics counterbalancing this system include plasminogen activator inhibitor-1 (PAI-1), which inhibits tPA and uPA, α-2 antiplasmin (α2AP), which inhibits plasmin, and thrombin activatable fibrinolysis inhibitor, which inhibits the conversion of fibrin to FDP. Inherited disorders of the fibrinolytic pathway are rare and primarily have hemorrhagic phenotypes in humans: PAI-1 deficiency, α2AP deficiency, and Quebec platelet disorder. Patients with these disorders are usually treated for bleeds or receive prophylaxis to prevent bleeds in the surgical setting, with pharmacological antifibrinolytics such as aminocaproic acid and tranexamic acid. Disorders of the fibrinolytic pathway with fibrin deposition are extremely rare, mostly noted in patients with plasminogen deficiency, who have more recently benefited from advances in human plasma-derived plasminogen concentrates administered intravenously or locally. These disorders can be very difficult to diagnose using conventional or even specialized coagulation testing, as testing can be nonspecific or have low sensitivity. Testing of the corresponding protein's activity and antigen (where applicable) can be obtained in specialized centres, and routine laboratory measures are not diagnostic. Genetic testing of the pathogenic mutations is recommended in patients with a high suspicion of an inherited disorder of the fibrinolytic pathway.","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294437","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

Causal Relationships of Circulating Inflammatory Proteins and Portal Vein Thrombosis: A Mendelian Randomization Study 循环炎症蛋白与门静脉血栓的因果关系：孟德尔随机研究

IF 5.7 2区医学

Seminars in thrombosis and hemostasis Pub Date : 2024-09-18 DOI: 10.1055/s-0044-1790259

Bihui Zhang, Ziping Yao, Pengyu Li, Guochen Niu, Ziguang Yan, Kang She, Gong Cheng, Min Yang

{"title":"Causal Relationships of Circulating Inflammatory Proteins and Portal Vein Thrombosis: A Mendelian Randomization Study","authors":"Bihui Zhang, Ziping Yao, Pengyu Li, Guochen Niu, Ziguang Yan, Kang She, Gong Cheng, Min Yang","doi":"10.1055/s-0044-1790259","DOIUrl":"https://doi.org/10.1055/s-0044-1790259","url":null,"abstract":"Portal vein thrombosis (PVT) is commonly encountered in patients with cirrhosis, challenging our understanding of its development, particularly the ambiguous contribution of inflammation. This study utilized Mendelian randomization (MR) to explore the causal impact of circulating inflammatory markers on PVT. Employing a two-sample MR framework, we merged genome-wide association study (GWAS) meta-analysis findings of 91 inflammation-associated proteins with independent PVT data from the FinnGen consortium's R10 release. A replication analysis was performed using a distinct GWAS dataset from the UK Biobank. Inverse variance weighting, MR-Egger regression, weighted median estimator, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier were used for analysis, supplemented by multivariable MR (MVMR) to adjust for cirrhosis effects. Findings indicate a significant inverse association between the genetically inferred concentration of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and PVT risk, evidenced by an odds ratio (OR) of 0.37 (95% confidence interval [CI]: 0.21–0.67; p = 9.2 × 10−4; adjusted for multiple testing p = 0.084). This association was corroborated in the replication phase (OR = 0.39, 95% CI: 0.17–0.93; p = 0.03) and through MVMR analysis (OR = 0.34, 95% CI: 0.15–0.79; p = 0.012). Sensitivity analyses disclosed no evidence of heterogeneity or pleiotropy. Our investigation emphasizes the 4E-BP1 as a protective factor against PVT, underscoring its potential relevance in understanding PVT pathogenesis and its implications for diagnosis and therapy. ","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249495","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