Hamostaseologie最新文献_第8页

A Novel Fibrinogen Mutation p.BβAla68Asp Causes an Inherited Dysfibrinogenemia. 新型纤维蛋白原突变 p.BβAla68Asp 导致遗传性纤维蛋白原不良血症。

IF 3.2 4区医学

Hamostaseologie Pub Date : 2023-12-01 Epub Date: 2023-07-29 DOI: 10.1055/a-2116-8957

Kaiqi Jia, Manlin Zeng, Xiaoyong Zheng, Haixiao Xie, Lihong Yang, Yaosheng Xie, Mingshan Wang

{"title":"A Novel Fibrinogen Mutation p.BβAla68Asp Causes an Inherited Dysfibrinogenemia.","authors":"Kaiqi Jia, Manlin Zeng, Xiaoyong Zheng, Haixiao Xie, Lihong Yang, Yaosheng Xie, Mingshan Wang","doi":"10.1055/a-2116-8957","DOIUrl":"10.1055/a-2116-8957","url":null,"abstract":"Objective: Our study aimed to analyze the phenotype and genotype of a pedigree with inherited dysfibrinogenemia, and preliminarily elucidate the probable pathogenesis.Methods: The one-stage clotting method was used to test the fibrinogen activity (FIB:C), whereas immunoturbidimetry was performed to quantify the fibrinogen antigen (FIB:Ag). Furthermore, DNA sequence analysis was conducted to confirm the site of mutation. Conservation analysis and protein model analysis were performed using online bioinformatics software.Results: The FIB:C and FIB:Ag of the proband were 1.28 and 2.20 g/L, respectively. Gene analysis revealed a heterozygous c.293C > A (p.BβAla68Asp) mutation in FGB. Bioinformatics and modeling analysis suggested that the missense mutation could potentially have a deleterious effect on fibrinogen.Conclusion: The BβAla68Asp mutation in exon 2 of FGB may account for the reduced FIB:C levels observed in the pedigree. To our knowledge, this point mutation is the first report in the world.","PeriodicalId":55074,"journal":{"name":"Hamostaseologie","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10265836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Genetic Analysis of Hereditary Coagulation Factor V Deficiency in Two Chinese Families Caused by Compound Heterozygous Mutations. 由复合杂合突变导致的两个中国家庭遗传性凝血因子 V 缺乏症的基因分析

IF 3.2 4区医学

Hamostaseologie Pub Date : 2023-12-01 Epub Date: 2023-06-15 DOI: 10.1055/a-2086-4328

Yuan Chen, Ke Zhang, Yanhui Jin, Manlin Zeng, Kaiqi Jia, Lihong Yang, Mingshan Wang

{"title":"Genetic Analysis of Hereditary Coagulation Factor V Deficiency in Two Chinese Families Caused by Compound Heterozygous Mutations.","authors":"Yuan Chen, Ke Zhang, Yanhui Jin, Manlin Zeng, Kaiqi Jia, Lihong Yang, Mingshan Wang","doi":"10.1055/a-2086-4328","DOIUrl":"10.1055/a-2086-4328","url":null,"abstract":"Objective: This study aims to provide a preliminary discussion of the molecular basis of FV deficiency caused by compound heterozygous mutations in two Chinese families.Methods: Relative coagulation index was measured by the one-stage clotting method and the FV:Ag was measured by ELISA. All exons and flanking regions of the F5 gene were amplified by PCR and directly sequenced. ClustalX-2.1-win was used to analyze the conservation of mutations. The online software was used to predict the pathogenicity of mutations. PyMOL was used to analyze the variation in the spatial structure of the FV protein before and after mutations. Calibrated automated thrombogram was used to analyze the function of the mutant protein.Results: Phenotyping suggested that both probands had a simultaneous decrease in FV:C and FV:Ag. Their genetic tests showed that proband A had a missense mutation p.Ser111Ile in exon 3 and a polymorphism p.Arg2222Gly in exon 25. At the same time, the proband B had a missense mutation p.Asp96His in exon 3 and a frame-shift mutation p.Pro798Leufs*13 in exon 13. Meanwhile, the p.Ser111Ile is conserved among homologous species. The bioinformatics and protein model analysis revealed that p.Ser111Ile and p.Pro798Leufs*13 were pathogenic and could affect the structure of the FV protein. The thrombin generation test revealed that the clotting function of proband A and B had been affected.Conclusion: These four mutations may be responsible for the reduction of FV levels in two Chinese families. Moreover, the p.Ser111Ile mutation is a novel pathogenic variant that has not been reported.","PeriodicalId":55074,"journal":{"name":"Hamostaseologie","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9642940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Erratum: A Novel Fibrinogen Mutation p.BβAla68Asp Causes an Inherited Dysfibrinogenemia. 更正：一种新型纤维蛋白原突变 p.BβAla68Asp 导致遗传性纤维蛋白原不良血症。

IF 3.2 4区医学

Hamostaseologie Pub Date : 2023-12-01 Epub Date: 2023-12-14 DOI: 10.1055/a-2218-6919

Kaiqi Jia, Manlin Zeng, Xiaoyong Zheng, Haixiao Xie, Lihong Yang, Yaosheng Xie, Mingshan Wang

引用次数: 0

Fibrinogen Bonn (p. Arg510Cys) in the Aα-Chain Is Associated with High Risk of Venous Thrombosis. Aα 链中的纤维蛋白原 Bonn（p. Arg510Cys）与静脉血栓的高风险有关。

IF 3.2 4区医学

Hamostaseologie Pub Date : 2023-12-01 Epub Date: 2023-07-13 DOI: 10.1055/a-2094-7191

V Ivaškevičius, A Biswas, S Singh, U Stulpinaitė, S Reda, H Rühl, B Pezeshkpoor, A Pavlova, J Oldenburg

{"title":"Fibrinogen Bonn (p. Arg510Cys) in the Aα-Chain Is Associated with High Risk of Venous Thrombosis.","authors":"V Ivaškevičius, A Biswas, S Singh, U Stulpinaitė, S Reda, H Rühl, B Pezeshkpoor, A Pavlova, J Oldenburg","doi":"10.1055/a-2094-7191","DOIUrl":"10.1055/a-2094-7191","url":null,"abstract":"Introduction: Inherited dysfibrinogenemia is a qualitative defect of fibrinogen caused by various mutations among three fibrinogen genes. Dysfibrinogenemia can be associated with an increased risk of thrombosis, bleeding, or both. Here, we report a 36-year-old female with dysfibrinogenemia who experienced two successful pregnancies under thromboprophylaxis after cerebral venous sinus thrombosis (CVST).Patients and methods: In addition to plasmatic coagulation tests, fibrinogen genes FGA, FGB, and FGG were screened using direct genomic DNA sequencing. The structural-functional implications of the detected mutation were analyzed in silico.Results: Inherited dysfibrinogenemia was diagnosed in an index patient after CVST in a risk situation. Anticoagulation with warfarin was stopped after 12 months when the first pregnancy was planned. Pregnancy and spontaneous delivery (2020) was uncomplicated. A second pregnancy was interrupted because of acute cytomegalovirus infection and the third pregnancy was successful in 2022. Pregnancies were accompanied by thromboprophylaxis with enoxaparin 40 mg once daily until 6 weeks postpartum. Substitution of fibrinogen has not become necessary in the index patient so far. Genetic analysis revealed a novel missense mutation (p. Arg510Cys) in the FGA gene (\"fibrinogen Bonn\") in the index patient, as well as an asymptomatic sister, and their father who experienced recurrent pulmonary embolism. Surface exposure of wild-type Arg510 suggested the mutated Cys510 to form nonnative disulfide bonds with surface-exposed reactive cysteines from other plasma proteins like albumin leading to formation of aggregates and impaired fibrinolysis.Conclusions: Fibrinogen Bonn might be associated with an increased risk of thrombosis, possibly due to impaired polymerization.","PeriodicalId":55074,"journal":{"name":"Hamostaseologie","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9831780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Factor XIII and Endothelial Dysfunction in Patients with Systemic Sclerosis. 因子 XIII 与系统性硬化症患者的内皮功能障碍

IF 3.2 4区医学

Hamostaseologie Pub Date : 2023-12-01 Epub Date: 2023-05-01 DOI: 10.1055/a-2018-7014

Sonja Alesci, Matthias Wahle, Andrea Himsel, Wolfgang Miesbach

{"title":"Factor XIII and Endothelial Dysfunction in Patients with Systemic Sclerosis.","authors":"Sonja Alesci, Matthias Wahle, Andrea Himsel, Wolfgang Miesbach","doi":"10.1055/a-2018-7014","DOIUrl":"10.1055/a-2018-7014","url":null,"abstract":"Systemic sclerosis (SSc, scleroderma) is a severe autoimmune connective tissue disease which affects the skin and internal organs. There has been evidence that coagulation factor XIII (FXIII) has a positive impact on clinical results in patients with SSc. In a single-center cohort study, we investigated the relationship between coagulation FXIII, endothelial dysfunction, and skin infection in SSc. Fifty-six patients could be included and were divided into two groups (with and without scleroderma). Markers of inflammation, coagulation, and endothelial dysfunction like C-reactive protein, leucocytes, fibrinogen, FVIII, VWF-Ag (von Willebrand factor antigen), D-dimers, and vascular endothelial growth factor were analyzed as well as MRSS (modified Rodnan skin scores) data were evaluated. Reduced daily activities were evaluated by the Scleroderma Health Assessment Questionnaire (SHAQ). There were no significant correlations between FXIII activity, MRSS, and SHAQ score. There were correlations between FXIII activity and Raynaud's phenomenon-related symptoms and a weak but not significant positive correlation with the level of pain. A significant correlation between VWF-Ag and lung-associated complaints (n = 56; p = 0.41, p < 0.0001) was found. Moreover, the study showed a correlation between VWF-Ag and MRSS (r [N = 48] = 0.4, p = 0.01), which means that higher VWF-Ag levels come along with more severe skin involvement. A trend toward a negative correlation between FXIII activity and VWF-Ag as marker of endothelial dysfunction was found (r [N = 56] = - 0.20, p = 0.15). In our cohort, there is no FXIII deficiency in patients with SSc. FXIII might have a role in improving cutaneous manifestations indirectly by means of a moderating influence on endothelial dysfunction. Further clinical evaluation is needed.","PeriodicalId":55074,"journal":{"name":"Hamostaseologie","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9763598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Clinical Characterization and Molecular Analysis of Fourteen Chinese Patients with Factor V Deficiency. 十四名中国因子 V 缺乏症患者的临床特征和分子分析

IF 3.2 4区医学

Hamostaseologie Pub Date : 2023-12-01 Epub Date: 2023-09-15 DOI: 10.1055/a-2146-9540

Ke Zhang, Longying Ye, Yanhui Jin, Yuan Chen, Manlin Zeng, Kaiqi Jia, Lihong Yang, Mingshan Wang

{"title":"Clinical Characterization and Molecular Analysis of Fourteen Chinese Patients with Factor V Deficiency.","authors":"Ke Zhang, Longying Ye, Yanhui Jin, Yuan Chen, Manlin Zeng, Kaiqi Jia, Lihong Yang, Mingshan Wang","doi":"10.1055/a-2146-9540","DOIUrl":"10.1055/a-2146-9540","url":null,"abstract":"Introduction: Coagulation factor V (FV) functions as a vital cofactor that performs procoagulant roles in the coagulation system. We investigated 14 unrelated patients whose plasma FV levels were all below the reference range.Methods: FV activity (FV:C) and FV antigen were detected by one-stage clotting and ELISA, respectively. All 25 exons of the F5 gene in patients were amplified by the PCR, and they were sequenced directly. Haplotype analysis was performed with different polymorphisms on F5. Protein modeling was applied to analyze the potential molecular mechanisms.Results: Of five patients with higher FV levels (FV:C > 10%), only one had minor bleeding symptoms. In contrast, of the remaining eight patients with lower FV levels (FV:C < 10%), six showed various bleeding manifestations. A total of 10 mutations were detected from 14 patients (6 were novel mutations). Interestingly, the homozygous p.Phe190Ser was found in five pedigrees, and haplotype analysis showed that they shared almost the same haplotype, indicating the common origin rather than a hotspot mutation. In silico analysis preliminarily investigated the potential pathogenic mechanism of the mutation. Modeling analysis showed that all six missense mutations would lead to conformational alterations in the FV protein. Among them, three (p.Gly1715Ser, p.Ser1753Arg, and p.Asp68His) would decrease hydrogen bonds.Conclusion: This is the largest genetic analysis of a single cohort of FV deficiency in Chinese. The study demonstrated that FV levels tended to be correlated with the probability of hemorrhage. The identification of a large number of unique FV-deficient pedigrees highlighted the screening for mutations in F5.","PeriodicalId":55074,"journal":{"name":"Hamostaseologie","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

[Basics for the Use of Andexanet]. [安己酮的使用基础]。

IF 3.2 4区医学

Hamostaseologie Pub Date : 2023-12-01 Epub Date: 2023-10-09 DOI: 10.1055/a-2136-2391

J Koscielny, I Birschmann, R Bauersachs, D Trenk, F Langer, P Möhnle, J Beyer-Westendorf

{"title":"[Basics for the Use of Andexanet].","authors":"J Koscielny, I Birschmann, R Bauersachs, D Trenk, F Langer, P Möhnle, J Beyer-Westendorf","doi":"10.1055/a-2136-2391","DOIUrl":"10.1055/a-2136-2391","url":null,"abstract":"Background: For life-threatening or uncontrollable bleeding in association with the thrombin inhibitor dabigatran, the monoclonal antibody fragment idarucizumab is available, and for bleeding in association with the direct factor Xa inhibitors rivaroxaban or apixaban, the modified recombinant FXa protein andexanet is available for reversal. These antidotes represent emergency drugs that are typically used only after performing guideline-compliant multimodal measures.Methods: An interdisciplinary group of experienced experts in the fields of angiology, hematology, internal medicine, clinical pharmacology, laboratory medicine, transfusion medicine, anesthesiology, intensive care, and hemostaseology developed recommendations relevant to daily clinical practice based on the current scientific evidence.Results: Reversal of oral anticoagulants should be considered for severe bleeding in the following situations: (1) life-threatening bleeding or refractory hemorrhagic shock, (2) intracerebral bleeding, or (3) endoscopically unstoppable gastrointestinal bleeding. After successful hemostasis, anticoagulation (e.g., direct oral anticoagulant, vitamin K antagonist, and heparin) should be resumed promptly, taking into account individual bleeding and thromboembolic risk.Discussion: This article aims to facilitate the management of patients with andexanet by all medical disciplines involved, thereby ensuring optimal care of patients during bleeding episodes.","PeriodicalId":55074,"journal":{"name":"Hamostaseologie","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

GTH News. GTH 新闻。

IF 3.2 4区医学

Hamostaseologie Pub Date : 2023-12-01 Epub Date: 2023-12-14 DOI: 10.1055/s-0043-1777814

引用次数: 0

Leichte Schlaganfälle: Thrombolyse und routinemäßige medi-zinische Versorgung im Vergleich. 轻度中风：血栓溶解和常规医疗护理的比较。

IF 3.2 4区医学

Hamostaseologie Pub Date : 2023-10-01 Epub Date: 2023-10-19 DOI: 10.1055/s-0043-1776436

引用次数: 0

Potentials of Endothelial Colony-Forming Cells: Applications in Hemostasis and Thrombosis Disorders, from Unveiling Disease Pathophysiology to Cell Therapy. 内皮集落形成细胞的潜力：在止血和血栓形成疾病中的应用，从揭示疾病病理生理学到细胞治疗。

IF 3.2 4区医学

Hamostaseologie Pub Date : 2023-10-01 Epub Date: 2023-10-19 DOI: 10.1055/a-2101-5936

Nadine Schwarz, Hamideh Yadegari

{"title":"Potentials of Endothelial Colony-Forming Cells: Applications in Hemostasis and Thrombosis Disorders, from Unveiling Disease Pathophysiology to Cell Therapy.","authors":"Nadine Schwarz, Hamideh Yadegari","doi":"10.1055/a-2101-5936","DOIUrl":"10.1055/a-2101-5936","url":null,"abstract":"Endothelial colony-forming cells (ECFCs) are endothelial progenitor cells circulating in a limited number in peripheral blood. They can give rise to mature endothelial cells (ECs) and, with intrinsically high proliferative potency, contribute to forming new blood vessels and restoring the damaged endothelium in vivo. ECFCs can be isolated from peripheral blood or umbilical cord and cultured to generate large amounts of autologous ECs in vitro. Upon differentiation in culture, ECFCs are excellent surrogates for mature ECs showing the same phenotypic, genotypic, and functional features. In the last two decades, the ECFCs from various vascular disease patients have been widely used to study the diseases' pathophysiology ex vivo and develop cell-based therapeutic approaches, including vascular regenerative therapy, tissue engineering, and gene therapy. In the current review, we will provide an updated overview of past studies, which have used ECFCs to elucidate the molecular mechanisms underlying the pathogenesis of hemostatic disorders in basic research. Additionally, we summarize preceding studies demonstrating the utility of ECFCs as cellular tools for diagnostic or therapeutic clinical applications in thrombosis and hemostasis.","PeriodicalId":55074,"journal":{"name":"Hamostaseologie","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49685277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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