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

{"title":"Novel compound heterozygous mutation of the KNG1 gene associated with severe HMWK deficiency in a Chinese pedigree.","authors":"Juan Huang, Wujiao Li, Ying Wang, Weiwei Xiao, Wei Liu, Bing Li, Leonardo Brandao, Xiaoying Fu","doi":"10.1097/MBC.0000000000001412","DOIUrl":"10.1097/MBC.0000000000001412","url":null,"abstract":"<p><strong>Objective: </strong>This study identifies and characterizes the novel compound heterozygous mutations in the KNG1 gene responsible for severe high molecular weight kininogen (HMWK) deficiency in a 3-year-old Chinese boy.</p><p><strong>Methods: </strong>The proband was identified during preoperative screening due to an isolated, prolonged activated partial thromboplastin time (APTT) without bleeding symptoms. Coagulation profiles, including thromboelastography (TEG), were analyzed. HMWK antigen (HMWK:Ag) levels were quantified by ELISA. Genetic analysis was performed using whole-exome and Sanger sequencing of the KNG1 gene in the proband and his parents. The pathogenicity of the novel variant was assessed according to ACMG/AMP guidelines.</p><p><strong>Results: </strong>Coagulation tests revealed a significantly prolonged APTT and a delayed R time on TEG, which was not corrected with extended incubation. HMWK:Ag levels were severely reduced (1.7 μg/ml) in the proband. Genetic analysis identified compound heterozygous mutations in KNG1: a novel missense variant in exon 5 (c.611C>T, p.Thr204Met) and a known nonsense variant in exon 6 (c.718C>T, p.Arg240*). Bioinformatic tools predicted the p.Thr204Met variant to be deleterious, and it was classified as \"Likely Pathogenic.\" The mutations were inherited in trans, confirming the genetic basis of the HMWK deficiency.</p><p><strong>Conclusion: </strong>We report a novel compound heterozygous mutation (c.611C>T and c.718C>T) in the KNG1 gene causing severe HMWK deficiency. This case expands the mutational spectrum of this ultra-rare disorder and highlights that its primary clinical significance is an isolated APTT prolongation without a bleeding diathesis. Genetic diagnosis is crucial to avoid unnecessary treatments, surgical delays, and exposure to blood products in such patients.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"127-132"},"PeriodicalIF":1.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438760","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":"Impaired clot formation and hemostasis in experimental traumatic hemorrhage model.","authors":"Marcus Wannberg, Iva Pruner, Apostolos Taxiarchis, Anton Razuvajev, Jovan Antovic, Carl-Magnus Wahlgren","doi":"10.1097/MBC.0000000000001411","DOIUrl":"10.1097/MBC.0000000000001411","url":null,"abstract":"<p><strong>Objective: </strong>Uncontrolled hemorrhage with hemostatic derangement still represents a major preventable cause of death following severe traumatic injury. The purpose of this experimental study was to further investigate the overall hemostasis potential and clot formation after severe traumatic hemorrhage.</p><p><strong>Methods: </strong>Male New Zealand white rabbits ( n  = 12) were subjected to traumatic injury with 40% hemorrhage of their estimated blood volume. The rate of thrombin generation was measured by calibrated automated thrombogram assay, overall hemostatic potential (OHP) by fibrin-aggregation on spectrophotometer, and microvesicles using flow cytometry. The clot structure was analyzed using scanning electron microscopy (SEM).</p><p><strong>Results: </strong>After traumatic hemorrhage, standard laboratory coagulation parameters showed decreased platelet count and fibrinogen, and increased INR and lactate. The OHP and overall coagulation potential (OCP) declined by 59% ( P  < 0.001) and 51% ( P  < 0,001), respectively. Overall fibrinolytic potential increased from 82% to 86% ( P  = 0.008). Platelet derived CD9 positive microvesicles decreased by 84% ( P  = 0.002). Endogenous thrombin potential decreased from 483 RFU/min to 383 RFU/min ( P  = 0.005). SEM analysis of the fibrin clot structure showed a more porous clot with a decrease in fiber diameter from 72 μm to 56 μm ( P  = 0.002).</p><p><strong>Conclusions: </strong>This experimental study provides important aspects on coagulopathy and clot structure after traumatic hemorrhage including reduced thrombin generation and hyperfibrinolysis resulting in a more porous fibrin clot with lower density and thinner fibers. The methods used may be applied in the clinical research setting to gain further insights about hemostasis and clot formation for targeted therapy after traumatic hemorrhage.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"79-86"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208494","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":"Diagnostic challenges in inherited platelet disorders in sub-Saharan Africa: first clinical case study of seven patients in Senegal.","authors":"Sokhna Aïssatou Touré, Aminata Faye, Abderamane Yacoub Hadje Kaltam, Diariatou Sy, Moussa Seck, Ndeye Khady Diagne, Assane Diouf, Alioune Badara Diallo, Mohamed Keita, Oumar Diallo, Diama Samb, Blaise Felix Faye, Abibatou Sall, Awa Oumar Touré, Saliou Diop","doi":"10.1097/MBC.0000000000001408","DOIUrl":"10.1097/MBC.0000000000001408","url":null,"abstract":"<p><strong>Introduction: </strong>Constitutional thrombopathies, also known as inherited platelet disorders (IPDs), represent a complex and heterogeneous group of bleeding disorders. These conditions are still poorly documented in resource-limited settings, particularly in sub-Saharan Africa. This study was initiated with the primary objective of confirming suspected cases of IPD in Senegal.</p><p><strong>Methodology: </strong>We conducted an observational study of all suspected cases of constitutional thrombopathy at the clinical hematology department in Dakar. Each patient provided written consent, and complete clinical files were obtained. We analyzed clinical parameters such as bleeding antecedent, history of care, first symptoms, bleeding profile, ISTH-SSC Bleeding Assessment Tool (BAT), and any complications related to the disorder.Biological assessments included platelet counts, blood smears, PT, aPTT, fibrinogen levels, coagulation factor assays, platelet aggregation testing using five agonists (collagen, ADP, AA, epinephrine, and ristocetin), and platelet immunophenotyping by flow cytometry (FC).</p><p><strong>Results: </strong>We identified ten cases, of which seven were included in this study. All patients were from consanguineous marriages, and only two had no family history of bleeding. Clinical manifestations were predominantly mucosal hemorrhages. All patients had elevated ISTH-SSC BAT.Platelet aggregation and immunophenotyping confirmed a Bernard-Soulier syndrome profile in one patient and a Glanzmann thrombasthenia in four patients. The remaining two patients exhibited profiles suggestive of GPVI/α2β1 integrin and P2Y1/P2Y12 receptor deficiencies.</p><p><strong>Conclusion: </strong>This first study conducted locally in sub-Saharan Africa highlights the complexity of diagnosing inherited platelet disorders and the challenges of implementing light transmission aggregometry and platelet immunophenotyping in resource-limited countries.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"74-78"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109587","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":"A novel missense variant (c.1172A>T, p.Asn391Ile) in the gamma chain of fibrinogen causing hypodysfibrinogenemia in an asymptomatic Danish family and review of adjacent variants.","authors":"Mustafa Vakur Bor, Inge Søkilde Pedersen, Moniek P M de Maat, Søren Risom Kristensen","doi":"10.1097/MBC.0000000000001415","DOIUrl":"10.1097/MBC.0000000000001415","url":null,"abstract":"<p><p>Congenital fibrinogen disorders are rare. We describe a novel fibrinogen γ-chain variant and review adjacent variants to contextualize its clinical significance. A woman investigated for infertility and her mother underwent hemostatic evaluation including functional, antigenic fibrinogen, and fibrin turbidity assays. Whole-exome sequencing (WES) was performed. Both asymptomatic individuals had hypodysfibrinogenemia with disproportionately reduced functional and antigenic fibrinogen and impaired fibrin polymerization with prolonged lag phase and reduced maximal slope (Vmax). WES revealed a novel heterozygous FGG missense variant, c.1172A>T (p.Asn391Ile; γ[365]Asn>Ile), in both individuals. According to ISTH-SSC guideline, both met subtype 4C (mild hypodysfibrinogenemia). Across 11 published cases with variants in γ361-369, six showed impaired fibrin polymerization and phenotypes ranged from bleeding ( n  = 6) and venous thrombosis ( n  = 2) to asymptomatic ( n  = 2) and hepatic fibrinogen storage disease ( n  = 1). FGG p.Asn391Ile variant is associated with hypodysfibrinogenemia and impaired fibrin polymerization, but current evidence is insufficient to define its clinical phenotype.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"115-120"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152098","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":"Nonsynthetic platelet-like products: methods and clinical potential in hemorrhage control.","authors":"Hassan Mansouritorghabeh","doi":"10.1097/MBC.0000000000001414","DOIUrl":"10.1097/MBC.0000000000001414","url":null,"abstract":"<p><p>Uncontrolled bleeding remains a leading cause of preventable death in trauma, and military medicine, underscoring the critical need for effective, accessible available hemostatic agents. While conventional platelet transfusions are indispensable for promoting primary hemostasis, they present several limitations, including short shelf life, logistical challenges, and transfusion-related risks. This review of evidence was done to obtain state-of-the-art data in this field. Hence, this scoping review pays to nonsynthetic platelet-like products, such as platelet microparticles and lyophilized platelet derivatives, which have emerged with promising hemostatic properties. Platelet microparticles, derived from activated platelets, exhibit potent procoagulant activity by contributing to both intrinsic and extrinsic coagulation pathways. Lyophilized platelet products, exemplified by thrombosomes, offer extended shelf life, room-temperature stability, and rapid hemostatic action, making them particularly valuable in prehospital and austere environments. Platelet lysate and PRF, while predominantly explored in regenerative medicine, have under-investigated potential as topical hemostatic agents. Despite encouraging preclinical and early clinical data for some of these products, challenges remain in terms of scalability, regulatory approval, and standardized clinical evaluation. Further research, particularly into platelet lysate and PRF, is warranted to validate their role in hemorrhage control. Nonsynthetic platelet-like products may represent a transformative approach in the management of life-threatening bleeding.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"61-73"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204577","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":"Isolated hematuria with ureterolithiasis in an infant with late-onset vitamin K deficiency bleeding.","authors":"Supapitch Chanthong, Rungrote Natesirinilkul, Chane Choed-Amphai, Nattaphorn Hongsawong, Pimlak Charoenkwan, Lalita Sathitsamitphong","doi":"10.1097/MBC.0000000000001419","DOIUrl":"10.1097/MBC.0000000000001419","url":null,"abstract":"<p><p>Late-onset vitamin K deficiency bleeding (VKDB) usually manifests as intracranial or gastrointestinal hemorrhage, and hematuria is rarely reported. We describe a 2-month-old, exclusively breastfed male infant who had received vitamin K prophylaxis at birth and developed gross hematuria on hospital day 9 while recovering from rotavirus gastroenteritis and cefotaxime-treated aspiration pneumonia. His prothrombin time was 136.9 s (INR 12.6), and activated partial thromboplastin time was 71.1 s. Factors II, VII, IX, and X were each <10%. Urine culture was sterile, and computed tomography demonstrated a right vesicoureteric calculus. A single 1-mg dose of parenteral vitamin K normalized coagulation parameters and resolved the hematuria within four hours. Rotavirus gastroenteritis and prolonged antibiotic use collectively depleted vitamin K stores in this infant despite prophylaxis. VKDB should be considered, particularly when potential risk factors for vitamin K depletion are recognized despite an atypical presentation, and vitamin K administration can be life-saving.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"111-114"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286885","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":"To test or not to test: JAK2V617F mutation prevalence in thrombophilia profiles.","authors":"Joseph Stenberg, Elizabeth Donovan, Devon Chabot-Richards, Marian Rollins-Raval","doi":"10.1097/MBC.0000000000001417","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001417","url":null,"abstract":"","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":"37 3","pages":"123-125"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597355","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":"Time-dependent coagulation declines in cold-stored whole blood: a paired in-vitro comparison of rotational thromboelastometry and SEER sonorheometry.","authors":"Edward Michelson, Bradford Ray, Susan H Watts, Leann Rodriguez, Diluma Kariyawasam, Paulina Castillo, Jesse Qiao","doi":"10.1097/MBC.0000000000001418","DOIUrl":"10.1097/MBC.0000000000001418","url":null,"abstract":"<p><strong>Introduction: </strong>The functional integrity of stored whole blood (WB) is critical for maintaining hemostatic potential during transfusion. While storage-related changes in coagulation components are known, comparative evaluation using viscoelastic and sonorheometric platforms remains limited. This in vitro study explores time-dependent changes in clotting dynamics during WB storage using rotational thromboelastometry (ROTEM) and sonic estimation of elasticity via resonance (SEER) sonorheometry (Quantra).</p><p><strong>Methods: </strong>WB from eight healthy donors was stored at 1-6 °C in citrate-phosphate-dextrose anticoagulant and sampled on Days 0, 1, 3, 7, 14, and 21. ROTEM parameters included INTEM/EXTEM/FIBTEM clotting time and amplitude; Quantra parameters included clotting time (CT), total clot stiffness (CS), platelet contribution (PCS), and fibrinogen contribution (FCS). Nonparametric statistics and effect sizes were used to assess temporal changes and agreement between platforms.</p><p><strong>Results: </strong>In this pilot in-vitro model ( n = 8) we observed progressive prolongation of clotting time and reduction in clot stiffness were observed across both platforms, as early as 1-3 days into storage. PCS declined significantly, while FCS showed modest reductions. ROTEM and Quantra demonstrated strong correlations in matched parameters, with consistent fixed biases noted in Bland-Altman analysis and a proportional bias with fibrinogen between the two methods.</p><p><strong>Discussion: </strong>Our experimental in vitro study of stored WB exhibits steady, time-dependent hemostatic deterioration, particularly in platelet function and clot initiation. These in-vitro observations reveal early declines in platelet-driven clot stiffness in our model and are hypothesis-generating for further laboratory and clinical evaluation.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"103-110"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208561","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":"Whole blood thrombin generation before and after eculizumab in a patient with hemolytic crisis due to paroxysmal nocturnal hemoglobinuria.","authors":"Angela Napolitano, Luca Spiezia, Cristiana Bulato, Ariela Hoxha, Paolo Simioni","doi":"10.1097/MBC.0000000000001407","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001407","url":null,"abstract":"","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":"37 3","pages":"121-123"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597332","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":"Dihydromyricetin exhibits potent antiplatelet activity with minimal impact on coagulation system: an in vitro study.","authors":"Yemei Shen, Xuemei Gao, Xuanrong Huan, Cui He, Yu Liu, Yuan Li","doi":"10.1097/MBC.0000000000001416","DOIUrl":"10.1097/MBC.0000000000001416","url":null,"abstract":"<p><p>This study aimed to systematically evaluate the antiplatelet activity of dihydromyricetin (DHM) and comprehensively investigate its effects on coagulation function within its therapeutically relevant concentration range. Using in-vitro experiments, we employed a panel of standard assays to assess the effects of DHM on platelet activation and aggregation induced by various agonists [adenosine diphosphate (ADP), arachidonic acid (AA), and collagen (COL)], as well as on agonist-independent adhesion and aggregation. Simultaneously, multidimensional techniques, including conventional coagulation tests, thromboelastography (TEG), and whole-blood dynamic coagulation analysis, were used to systematically evaluate the impact of DHM on the coagulation cascade and overall hemostatic dynamics. The results showed that DHM significantly inhibited platelet activation and aggregation in a concentration-dependent manner and effectively prevented their spontaneous adhesion and aggregation. Crucially, within the concentration range that exerted effective antiplatelet effects, DHM did not significantly affect any of the tested coagulation parameters, and no cytotoxicity was observed. These in-vitro findings suggest that DHM is a platelet-specific inhibitor, exerting potent antiplatelet effects while not interfering with normal physiological coagulation processes. Therefore, DHM shows potential as an antithrombotic candidate pending in-vivo studies with a potentially low risk of bleeding, providing crucial experimental evidence and a new direction for the development of safer antithrombotic strategies.</p>","PeriodicalId":520571,"journal":{"name":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","volume":" ","pages":"90-102"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204583","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}