Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis最新文献

{"title":"PROS1 Cys475Tyr mutation associated with a type III protein S deficiency pattern.","authors":"José A Mejias-Figueroa, Charlotte M Story, Michael B Streiff","doi":"10.1097/MBC.0000000000001438","DOIUrl":"10.1097/MBC.0000000000001438","url":null,"abstract":"<p><p>A 35-year-old woman presented with a deep vein thrombosis (DVT) and was diagnosed with protein S deficiency. She was treated with parenteral anticoagulation before switching to a direct oral anticoagulant. She presented to our practice 5 years later, where testing was repeated, demonstrating a type III deficiency pattern and a variant of uncertain significance in PROS1: c.1424G>A; p.Cys475Tyr. This cysteine residue participates in a disulfide bond in the sex hormone-binding globulin-like domain, which interacts with C4b-binding protein and is involved in several antithrombotic roles of protein S. This case report and the biochemical context support its pathogenicity.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"266-268"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13566446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148255450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mRNA expression and methylation rate of two antithrombotic genes, KLF2 and THBD , in patients with ischemic stroke and early onset ischemic stroke in comparison with healthy controls.","authors":"Zahra Sadat Hosseini, Abdoreza Ghoreishi, Mohammad Reza Ashoori, Mohammad Soleiman Soltanpour","doi":"10.1097/MBC.0000000000001440","DOIUrl":"10.1097/MBC.0000000000001440","url":null,"abstract":"<p><p>The most common type of stroke is ischemic stroke. Key regulators of thrombosis including KLF2, eNOS, TM and PAI-1 are considered as potential causes in ischemic stroke pathogenesis. This study examined gene expression and DNA methylation status of KLF2 and THBD genes in ischemic stroke patients. We selected 48 ischemic stroke patients and 48 healthy controls. Gene expression and methylation status of KLF2 and THBD genes were evaluated by real-time RT-PCR and MS-PCR, respectively. Clinical characteristics were also evaluated based on the methylation status of the patients. Statistical analysis was done using SPSS-26 software. mRNA expression of KLF2 ( P  = 0.0157) and THBD ( P  = 0.0070) was significantly reduced in ischemic stroke compared to the control. The hypermethylation of KLF2 and THBD genes significantly increased in ischemic stroke group ( P  = 0.026 and P  = 0.021, respectively). Moreover, significantly increased methylation of KLF2 and THBD genes were seen in early onset ischemic stroke group than control group ( P  < 0.05). Hypermethylation in KLF2 and THBD was significantly associated with the occurrence of global aphasia. Also, hypermethylation in KLF2 was associated with dysarthria. The binary logistic regression analysis showed that KLF2 methylation, THBD methylation, obesity and asthma significantly and independently associated with the occurrence of ischemic stroke. However, diabetes and smoking revealed borderline association. Our study identified hypermethylation in KLF2 and THBD genes as a novel risk marker for ischemic stroke development. So, appropriate management of hypermethylation in KLF2 and THBD genes may be considered as therapeutic strategies for ischemic stroke patients.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"250-257"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic microclot profiling: thromboelastography advances precision management in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.","authors":"Shafaq Saleem, Ahmad Hussain, Muhammad Haroon, Ahmad Raza, Umar Afzal, Muhammad Furqan Anwar, Samar Imran, Muhammad Usman Iqbal, Fatima Hajj","doi":"10.1097/MBC.0000000000001439","DOIUrl":"10.1097/MBC.0000000000001439","url":null,"abstract":"<p><p>Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) share overlapping symptoms, and emerging evidence implicates persistent fibrinoid microclots in their pathophysiology, contributing to impaired microcirculation. This review explores the role of microclots and evaluates thromboelastography (TEG) as a potential diagnostic tool. A comprehensive literature review was conducted using major biomedical databases. Studies indicate microclots are prevalent in both conditions. Long COVID patients demonstrate a TEG profile of increased clot strength (maximum amplitude) and reduced fibrinolysis (LY30), suggesting a persistent hypercoagulable state. Despite its advantages in real-time assessment, TEG interpretation faces challenges from preanalytical variability and a lack of standardized protocols. Promising therapeutic trials, including anticoagulants (e.g., apixaban) and fibrinolytics (e.g., lumbrokinase), require further validation. Technological advancements like AI-driven TEG analysis and portable devices could improve diagnostic precision. In conclusion, persistent microclots are a key pathophysiological feature. TEG provides a promising, novel approach for detecting coagulation abnormalities and could guide treatment, but requires standardization in future clinical trials. Future research should integrate multiomics biomarkers for precision therapeutics to improve patient outcomes.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"288-295"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SEER sonorheometry enhances fibrinolysis detection during liver transplantation with heparin.","authors":"Todd W Allen, Francesco Viola, Kenichi A Tanaka","doi":"10.1097/MBC.0000000000001441","DOIUrl":"10.1097/MBC.0000000000001441","url":null,"abstract":"<p><strong>Background: </strong>Whole blood viscoelastic tests (VETs) are key for detecting fibrinolysis during orthotopic liver transplantation (OLT). The Quantra System introduces a novel parameter, clot stability to lysis (CSL), for quantifying fibrinolysis. The objective was to assess CSL performance relative to established VET measures.</p><p><strong>Methods: </strong>Data were drawn from a multicenter, prospective study of adults undergoing OLT, with Quantra and ROTEM delta testing performed in parallel. This sub-analysis focused on fibrinolysis-positive samples, emphasizing discordant findings between platforms.</p><p><strong>Results: </strong>Among 125 enrolled patients, 13 intraoperative samples involving the use of heparin showed discordant results. Calibrated automated thrombinography revealed that Quantra reagents produce slower, reduced thrombin generation compared to ROTEM, diminishing thrombin activatable fibrinolysis inhibitor (TAFI) activity. This enhances sensitivity of Quantra to detect fibrinolysis in these samples.</p><p><strong>Conclusions: </strong>Quantra's CSL parameter demonstrated improved detection of fibrinolysis in heparinized samples and may support individualized fibrinolysis management during OLT. Broader clinical validation is warranted.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"279-282"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13566444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case of congenital thrombotic thrombocytopenic purpura presenting with renal dysfunction in adulthood caused by a novel compound heterozygous ADAMTS13 mutation.","authors":"Anzi Wang, Dongyun Su, Rong Chen, Li He, Ruiying Fu, Jiajia Yao","doi":"10.1097/MBC.0000000000001428","DOIUrl":"10.1097/MBC.0000000000001428","url":null,"abstract":"<p><p>Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare autosomal recessive genetic disorder caused by mutations in the ADAMTS13 gene. We report a 36-year-old male cTTP patient with three compound heterozygous mutations. The patient was admitted for acute thrombocytopenia, with a 5-year history of chronic thrombocytopenia and 3 months of renal dysfunction. Initially diagnosed with immune thrombocytopenia, he was treated with glucocorticoids and the thrombopoietin receptor agonist, which provided temporary relief but failed to prevent recurrent thrombocytopenia. Ultimately, cTTP was confirmed by severely reduced ADAMTS13 activity (3.81%), the absence of ADAMTS13 inhibitors, and the identification of compound heterozygous mutations, including one novel pathogenic variant. Genetic analysis of the entire family helped in the characterization of the inheritance of this mutation. The patient was treated with fresh frozen plasma and later with prophylactic infusions. No clinical relapses occurred during follow-up.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"261-265"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147978575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uterine fibroids as an underrecognized risk factor for venous thromboembolism: a narrative review.","authors":"Menna Megahed, Zunaira Zia Shah, Kumail A Razvi, Yazan Abdeen","doi":"10.1097/MBC.0000000000001436","DOIUrl":"10.1097/MBC.0000000000001436","url":null,"abstract":"<p><strong>Background: </strong>Uterine fibroids are a prevalent gynecologic condition traditionally associated with heavy menstrual bleeding and pelvic pressure. However, emerging evidence suggests that large uterine fibroids may also contribute to venous thromboembolism (VTE) by causing mechanical compression of pelvic veins and the inferior vena cava, leading to venous stasis and subsequent thrombosis. This narrative review aims to consolidate current knowledge, discuss diagnostic strategies and management approaches for fibroid-associated VTE, and raise clinical awareness about this often-overlooked complication.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted across PubMed, PubMed Central, Embase, Scopus, and Google Scholar from January 2000 to April 2024. Studies examining the relationship between uterine fibroids and VTE, including case reports, observational studies, reviews, and management guidelines, were included. A descriptive synthesis of findings was performed.</p><p><strong>Results: </strong>Twenty-four studies were included, demonstrating a consistent association between large uterine fibroids and increased VTE risk. Key mechanisms included venous compression, hormonal influences, and a fibroid-associated hypercoagulable state. Clinical presentations ranged from isolated deep vein thrombosis (DVT) to life-threatening pulmonary embolism (PE). Early diagnosis often relied on pelvic imaging such as ultrasound and MRI. Management strategies involved prompt anticoagulation, individualized surgical planning (primarily hysterectomy), and multidisciplinary coordination. In select cases, prophylactic anticoagulation was suggested for high-risk patients pending surgery.</p><p><strong>Conclusion: </strong>Uterine fibroids should be recognized as a potential etiology for unexplained VTE, particularly in women without classic risk factors. Early imaging, anticoagulation, and surgical intervention, when appropriate, can optimize outcomes. Further research is needed to establish standardized screening and management guidelines for this underrecognized cause of thromboembolic disease.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"283-287"},"PeriodicalIF":1.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of a commercial modified factor VIII bethesda inhibitor assay to current factor VIII inhibitor assay methods in a multicenter trial.","authors":"Andres E Mindiola Romero, Richard A Marlar, Marian A Rollins-Raval, Ian Burns, Elizabeth A Plumhoff","doi":"10.1097/MBC.0000000000001433","DOIUrl":"10.1097/MBC.0000000000001433","url":null,"abstract":"<p><p>Patients with hemophilia A may develop antibodies (also known as inhibitors) to factor VIII (FVIII) after exposure to treatment products. These antibodies inhibit FVIII function and interfere with treatment using FVIII replacement products. Interlaboratory variation of inhibitor assay results continue to be problematic for the management and treatment of patients with hemophilia A. A commercial FDA-cleared FVIII inhibitor kit (F8Inh Kit) has been developed to bring consistency to FVIII inhibitor assessment. The aim of this study was to compare the kit's performance to in-house methods for FVIII inhibitor quantification in 24 North American and European laboratories. We performed a comparative method study from Q4 2018 to Q1 2019. Each laboratory performed FVIII inhibitor assays on the test samples using their in-house method and using the F8Inh Kit per the validated and approved procedure outlined in the package insert. A total of 470 data sets were received, and the overall imprecision for all laboratories improved for the control mix when it was standardized using the PBI F8Inh Kit with a significant decrease in coefficient of variation relative to in-house methods. The F8Inh Kit provided a standardized method and reagent set showing significant potential for laboratories seeking to establish accurate and precise FVIII inhibitor measurements.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"207-219"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrin degradation products enhance plasmin activity and contribute to fibrinolysis during simulated trauma-induced coagulopathy.","authors":"Chang Yeop Han, Nathan Dow, Nathan J White","doi":"10.1097/MBC.0000000000001430","DOIUrl":"10.1097/MBC.0000000000001430","url":null,"abstract":"<p><strong>Objective: </strong>Fibrinolysis is an important component of trauma-induced coagulopathy (TIC) that is strongly associated with early mortality after injury. Yet, the mechanisms driving excessive fibrinolysis remain incompletely understood. We hypothesized that fibrin degradation products (FDPs) known to become elevated in the blood after trauma can actively contribute to TIC by promoting disordered clot formation and enhanced plasmin activity.</p><p><strong>Methods: </strong>Purified FDPs, fragments X, D, E, and D-dimer, were titrated into normal human plasma in vitro at physiologically relevant concentrations under normal and simulated TIC conditions. Rotational thromboelastometry (ROTEM) was used to assess their effects on clot initiation, formation, firmness, and lysis. Thrombin generation assays (TGA) and plasmin generation assays (PGA) were performed to measure enzymatic activity in the presence of each FDP. Key parameters included clotting time (CT), α-angle, maximum clot firmness (MCF), lysis index at 45 minutes (LI-45), maximum lysis (ML), time to peak plasmin activity, PGA slope and peak plasmin concentration.</p><p><strong>Results: </strong>Fragments D, X, and D-dimer increased clot lysis by ROTEM under TIC-like conditions. D-dimer and D fragments significantly accelerated plasmin generation judged by shortening PGA peak time, and increasing PGA slope and concentration, whereas thrombin generation was not different across all groups.</p><p><strong>Conclusions: </strong>Individual FDPs, including fragments D, X, and D-dimer, can contribute to TIC by increasing plasmin activity. Further studies in whole blood and trauma patient samples are warranted.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"184-189"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox-driven antiplatelet effect of snake venom phospholipase A2: VLPLA2 from Vipera lebetina venom as a new antithrombotic agent.","authors":"Amel Kadi-Saci, Fatima Laraba-Djebari","doi":"10.1097/MBC.0000000000001429","DOIUrl":"10.1097/MBC.0000000000001429","url":null,"abstract":"<p><strong>Background: </strong>Snake venom phospholipases A2 are multifunctional enzymes which modulate haemostatic balance. Their antithrombotic potential via redox-sensitive signalling pathways remains underexplored.</p><p><strong>Objectives: </strong>This study reports the redox-mediated antiplatelet effects of vipera l ebetina phospholipase A2 (VLPLA2), a phospholipase A2 purified from Vipera lebetina , we also assess its potential as a novel antithrombotic agent.</p><p><strong>Methodology: </strong>VLPLA2 was evaluated for its effects on human platelet aggregation, redox signalling pathways and antioxidant enzyme modulation. The involvement of VLPLA2 in platelet adhesion to fibrinogen was also investigated.</p><p><strong>Results: </strong>VLPLA2 strongly inhibited ADP-induced platelet aggregation and platelet adhesion to fibrinogen, probably by increasing catalase activity and reducing hydrogen peroxide levels, suggesting a compensatory redox response. The antiplatelet effect of VLPLA2 appears to be mediated by ROS overproduction, possibly via the involvement of nicotinamide adenine dinucleotide reduced phosphate (NADPH) oxidase signalling pathways. This redox imbalance leads to oxidative modifications of P2Y12 ADP receptor and GPIIb/IIIa fibrinogen receptor, consequently, avoiding their activation.</p><p><strong>Conclusions: </strong>Our data reveal a dual mechanism of VLPLA2 via enzymatic membrane phospholipid hydrolysis and oxidative modulation of platelet signalling pathways. VLPLA2 could be a promising candidate for the development of redox-targeted antithrombotic therapeutics.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"190-197"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe congenital factor X deficiency presenting with umbilical and subgaleal hemorrhage: a case report.","authors":"Ibrahim Kattoush, Haya Ewidat, Mohammed Alra'e, Osama Hazem Mahmoud Jabbarin, Mohammed Aldwaik","doi":"10.1097/MBC.0000000000001434","DOIUrl":"10.1097/MBC.0000000000001434","url":null,"abstract":"<p><p>Congenital factor X (FX) deficiency is an exceedingly rare hemorrhagic condition. Severe deficiency frequently manifests in early life and can lead to life-threatening hemorrhagic consequences, such as intracranial hemorrhage. Because of its infrequency and vague initial symptoms, early diagnosis is challenging. We report a case of a full-term female neonate who presented with persistent umbilical stump bleeding and progressive scalp swelling. Labs were consistent with hypocoagulability. Imaging of the head revealed a large subgaleal, subdural, and cerebellar hematomas. Coagulation factor measurement confirmed a severe congenital FX deficiency. The patient received vitamin K, fresh frozen plasma (FFP), blood transfusion, and was referred for management with replacement therapy. The patient was discharged in stable condition. Early neonatal bleeding, including umbilical and subgaleal hemorrhage, may be the initial manifestations of severe congenital FX deficiency, even in the absence of family history. Rapid diagnosis, proper replacement, and a multidisciplinary approach will ensure optimum outcomes.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"237-240"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}