Blood Coagulation & Fibrinolysis最新文献

Improved prevention of bleeding episodes with emicizumab in 3 patients with concomitant hemophilia A and von Willebrand disease. 埃米珠单抗能有效预防 3 名同时患有血友病 A 和冯-威廉氏病的患者的出血发作。

IF 1.2 4区医学

Blood Coagulation & Fibrinolysis Pub Date : 2024-09-05 DOI: 10.1097/MBC.0000000000001324

Kristin T Ansteatt, Jonathan C Roberts, Jackie M Helms, Michael D Tarantino

{"title":"Improved prevention of bleeding episodes with emicizumab in 3 patients with concomitant hemophilia A and von Willebrand disease.","authors":"Kristin T Ansteatt, Jonathan C Roberts, Jackie M Helms, Michael D Tarantino","doi":"10.1097/MBC.0000000000001324","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001324","url":null,"abstract":"The typical phenotype of hemophilia A (HA) is that of frequent bleeding episodes, up to several per month, unless prophylactic factor VIII (FVIII) replacement or alternatives are given. Related bleeding may be heightened in severity or frequency by co-morbid bleeding disorders. Based on the reported prevalence of von Willebrand disease (VWD) of up to 1% of the general population, the co-existence of HA and VWD occurs, but is likely less recognized. Prophylactic FVIII replacement may or may not adequately prevent bleeding in persons with HA and mild VWD, and plasma-derived concentrates containing FVIII and von Willebrand factor (VWF) may be used for more successful bleeding prophylaxis. However, therapy adherence remains problematic for many reasons, one being treatment via intravenous access. Emicizumab is a nonfactor subcutaneous prophylactic therapy for HA that may overcome this concern. We describe three patients, with severe HA and VWD, for whom regular FVIII/VWF prophylaxis was deemed inadequate. FVIII/VWF prophylaxis was replaced with weekly prophylactic injections of the bispecific monoclonal antibody, emicizumab. When the patients were transitioned to emicizumab, all experienced a significant reduction in their annualized bleed rate (ABR). Although the mechanism of action does not directly affect or replace VWF function, emicizumab may be an effective prophylaxis alternative to FVIII/VWF concentrate in patients with concomitant severe HA and VWD.","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153117","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

Cancer-associated thrombosis: the role of inherited thrombophilia. 癌症相关血栓形成：遗传性血栓性疾病的作用。

IF 1.2 4区医学

Blood Coagulation & Fibrinolysis Pub Date : 2024-09-01 Epub Date: 2024-07-26 DOI: 10.1097/MBC.0000000000001317

Anita Zia, Mahmood Shams, Ali Dabbagh, Milad Shahsavari, Akbar Dorgalaleh

引用次数: 0

Identification of HLA alleles involved in immune thrombotic thrombocytopenic purpura patients from Turkey. 土耳其免疫性血栓性血小板减少性紫癜患者的 HLA 等位基因鉴定。

IF 1.2 4区医学

Blood Coagulation & Fibrinolysis Pub Date : 2024-09-01 Epub Date: 2024-07-24 DOI: 10.1097/MBC.0000000000001318

Cevat İlteriş Kikili, Demet Kivanç, Damla Ortaboz, Hayriye Şentürk Çiftçi, Mustafa Murat Özbalak, Mustafa Nuri Yenerel, Meliha Nalçaci, Muhlis Cem Ar, Fatma Savran Oğuz, Sevgi Kalayoğlu Beşişik

{"title":"Identification of HLA alleles involved in immune thrombotic thrombocytopenic purpura patients from Turkey.","authors":"Cevat İlteriş Kikili, Demet Kivanç, Damla Ortaboz, Hayriye Şentürk Çiftçi, Mustafa Murat Özbalak, Mustafa Nuri Yenerel, Meliha Nalçaci, Muhlis Cem Ar, Fatma Savran Oğuz, Sevgi Kalayoğlu Beşişik","doi":"10.1097/MBC.0000000000001318","DOIUrl":"10.1097/MBC.0000000000001318","url":null,"abstract":"Thrombotic thrombocytopenic purpura (TTP) is one of the rare group disorders classified as thrombotic microangiopathies (TMAs). Approximately 90% of TTP developed immune-mediation by the formation of antibodies against the enzyme ADAMTS-13. The exact cause is unknown. To establish an association between human leukocyte antigen (HLA) and autoimmune basis, as susceptibility or protection against the disease, we contributed a study aiming to evaluate the role of HLA in immune-mediated TTP (iTTP). Considering epidemiological factors such as age, sex, ethnicity, and geographical origins, we contributed the study in our country, Turkey, which consist of a very heterogeneous population. Patients' data collection was retrospectively from electronic database on two University hospitals having big therapeutic apheresis service. Control arm was healthy people registered as stem cell donors matched in terms of age and sex. The frequency of HLA-DRB1 and HLA-DQB1 alleles between acquired TTP and the control group was compared using the chi-square method. Yates correction and logistic regression were performed on these results. A total of 75 iTTP patients and 150 healthy individuals enrolled to the study. HLA-DRB1∗11, HLA-DQB1∗03, HLA-DRB1∗11:01, HLA-DRB1∗14:01, HLA-DRB1∗13:05, HLA-DRB1∗11 + HLA-DQB1∗03 allele pair and HLA-DRB1∗15 + HLA- DQB1∗06 were proved to be susceptibility allele pairs for iTTP. HLA-DRB1∗15, HLA-DRB1∗01:01, HLA-DRB1∗07:01, HLA-DRB1∗13:01, HLA-DRB1∗14:54, HLA-DQB1∗05:01, HLA-DQB1∗02:02 and HLA-DRB1∗07 + HLA-DQB1∗02 allele pair were found to be protective against iTTP. Our findings support an association with iTTP across very heterogenous populations in Turkey.","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854671","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

Effect of hemolysis on D-dimer testing measured with the Improgen kit: is all manufacturer information correct? 溶血对使用改进型试剂盒测量的 D-二聚体检测的影响：制造商提供的所有信息是否正确？

IF 1.2 4区医学

Blood Coagulation & Fibrinolysis Pub Date : 2024-09-01 Epub Date: 2024-07-03 DOI: 10.1097/MBC.0000000000001316

Merve Sena Odabasi

{"title":"Effect of hemolysis on D-dimer testing measured with the Improgen kit: is all manufacturer information correct?","authors":"Merve Sena Odabasi","doi":"10.1097/MBC.0000000000001316","DOIUrl":"10.1097/MBC.0000000000001316","url":null,"abstract":"D-dimer is a fibrin degradation product and its measurement is affected by hemolysis. This study was designed to reveal the value of hemolysis affecting D-dimer in our laboratory. In this study, hemolysate samples obtained by both mechanical and freezing methods were used. D-dimer levels of all plasmas were measured with Improgen Diagnostic kit by immune-turbidimetric method. Numerical change in hemolyzed samples was evaluated by calculating the percentage difference, and clinically significant differences were evaluated by calculating the maximum acceptable bias (MAB). In the hemolysate study prepared by both freeze-thaw and mechanical methods, it was observed that low D-dimer levels did not exceed the total allowable error (TAE) (30%) up to +2 hemolysis (corresponds to hemoglobin = 1.01-2 g/l) and did not exceed the MAB (65%) even at +4 hemolysis (corresponds to hemoglobin = 1.01-2 g/l). High D-dimer levels did not exceed the limit values of both TAE (30%) and MAB (68%) even in +4 hemolysis. The D-dimer test was affected by lower levels of hemolysis compared to both other studies and the values in the kit insert (hemoglobin >5 g/l corresponds to +4 hemolysis index). We verified the hemolysis interference in the D-dimer test, which we thought was not compatible with the kit insert, under our own laboratory conditions. This is the first hemolysis interference study performed with the Improgen brand d-dimer kit. In samples with a hemolysis rate of +2 and above, it would be more accurate to reject the D-dimer result as a 'hemolyzed sample'.","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619262","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

Real-world clinical outcomes with fostamatinib for the treatment of refractory chronic immune thrombocytopenia: a single-center experience. 福斯塔替尼治疗难治性慢性免疫性血小板减少症的实际临床疗效：单中心经验。

IF 1.2 4区医学

Blood Coagulation & Fibrinolysis Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI: 10.1097/MBC.0000000000001319

Donald C Moore, Joseph B Elmes, Justin R Arnall, Mauricio Pineda-Roman

{"title":"Real-world clinical outcomes with fostamatinib for the treatment of refractory chronic immune thrombocytopenia: a single-center experience.","authors":"Donald C Moore, Joseph B Elmes, Justin R Arnall, Mauricio Pineda-Roman","doi":"10.1097/MBC.0000000000001319","DOIUrl":"10.1097/MBC.0000000000001319","url":null,"abstract":"Fostamatinib is a spleen tyrosine kinase inhibitor indicated for the treatment of chronic immune thrombocytopenia (ITP) unresponsive to a previous treatment. Real-world studies evaluating the utilization and effectiveness of fostamatinib outside the context of a clinical trial are lacking. The objective of this analysis was to evaluate the effectiveness of fostamatinib for the treatment of ITP in a real-world cohort. We conducted a single-center, retrospective, observational study to evaluate the effectiveness of fostamatinib for the treatment of ITP. The primary endpoint was durable response as defined by the American Society of Hematology ITP response criteria. Secondary endpoints included overall response rate, time to response, and safety. Subgroup analysis was performed to assess frequency of durable response in key subgroups of patients based on prior therapies. Thirty-one patients treated with fostamatinib for ITP were included in our analysis. Patients had received a median of four prior lines of therapy. Ten patients (32%) achieved a durable response. Most durable responders maintained their response at 24 months ( n = 7; 70%). The median time to response was 9 days. Four patients (13%) discontinued fostamatinib due to an adverse event. Subgroups who had higher rates of durable responses included those who had received two to three prior lines of therapy (40%), splenectomized patients (50%), and those who had not received prior rituximab (55%). Fostamatinib therapy in a real-world population of patients with heavily pretreated ITP led to a durable response in a third of patients, which was maintained for most responders.","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619264","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

Joint deficiency of coagulation factors VII and IX: a case report. 凝血因子 VII 和 IX 共同缺乏症：病例报告。

IF 1.2 4区医学

Blood Coagulation & Fibrinolysis Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI: 10.1097/MBC.0000000000001315

Jhon Alexander Avila Rueda, Cesar de la Hoz, Edgar Fabián Manrique-Hernández

{"title":"Joint deficiency of coagulation factors VII and IX: a case report.","authors":"Jhon Alexander Avila Rueda, Cesar de la Hoz, Edgar Fabián Manrique-Hernández","doi":"10.1097/MBC.0000000000001315","DOIUrl":"10.1097/MBC.0000000000001315","url":null,"abstract":"The diagnostic and therapeutic approach for an unusual clinical situation is presented. Twenty-three-year-old female patient is evaluated for hematuria and metrorrhagia. She reported irregular follow-up with hematology because of bleeding in childhood. She has also been receiving factor VII for 2 years, denying hospitalizations because of bleeding. Laboratory reported hb: 5.2 g/dl; platelets: 234 000/mm 3 ; PT: 100 s; PTT: 112 s, fibrinogen: 90 mg/dl without other alterations. Abdominal ultrasound reported uterine myoma, urinalysis was pathological. The gynecology indicated oral progesterone. She started antibiotic therapy, transfusion of red-blood cells, plasma, and cryoprecipitates and subsequently reported: factor VII: 2%, IX: 1% and VIII: 70%. She received factor VII-recombinant (rFVII), achieving resolution of bleeding. She was prescribed prophylactic rFVII and hematology monitoring. Readmission due to acute abdomen with Hb 5 g/dl, prolonged prothrombin time (PT)/partial thromboplastin time (PTT) and abdominal tomography reported hemoperitoneum. She received rFVII and required laparotomy and left oophorectomy. Then readmission to metrorrhagia, hb6 g/dl, prolonged PT/PTT and factor VII-IX of two coagulation factors were reported, without reports found in the literature consulted.","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619263","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

Protein S contributes to the paradoxical increase in thrombin generation by low-dose dabigatran in the presence of thrombomodulin. 在血栓调节蛋白存在的情况下，低剂量达比加群会增加凝血酶的生成，而蛋白 S 对这一矛盾现象起了作用。

IF 1.2 4区医学

Blood Coagulation & Fibrinolysis Pub Date : 2024-08-23 DOI: 10.1097/MBC.0000000000001320

Chi Zhang, Weixiang Chen, Yue Zhang, Tingbo Jiang

{"title":"Protein S contributes to the paradoxical increase in thrombin generation by low-dose dabigatran in the presence of thrombomodulin.","authors":"Chi Zhang, Weixiang Chen, Yue Zhang, Tingbo Jiang","doi":"10.1097/MBC.0000000000001320","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001320","url":null,"abstract":"Low dose of dabigatran paradoxically increased thrombin generation through inhibition of protein C activation. Protein S is a co-factor in the activation of protein C. However, the role of protein S in the enhancement of thrombin generation has not been addressed. Firstly, we measured thrombin generation by calibrated automated thrombinography (CAT) and prothrombin fragments 1+2 (F1+2) assays. Secondly, we assessed activated protein C (APC) formation in normal or protein S-deficient plasma spiking with dabigatran. Then, protein C activation was measured. Finally, heavy chain of factor Va (FVa) and its degradation products were detected by western blot. CAT assay showed that 70-141 ng/ml dabigatran paradoxically increased thrombin generation in normal plasma. However, higher concentrations of dabigatran (283 ng/ml) suppressed the level of ETP. F1+2 assay showed the similar results. In protein S-deficient or protein C-deficient plasma, the paradoxical increase in thrombin generation was absent. Level of generated APC was to a similar extent inhibited by dabigatran in normal and protein S-deficient plasma. Low-dose dabigatran inhibited the protein S-dependent inactivation of factor Va. Protein S participated in the paradoxical enhancement of thrombin generation in normal plasma spiking with low concentrations of dabigatran. Increased thrombin generation at low dabigatran can be explained by reduced thrombin-thrombomodulin mediated APC formation and subsequent reduced FVa inactivation that is protein S-dependent.","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153118","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

Effect of hyperbilirubinemia and phototherapy on apoptotic microparticle levels in neonates. 高胆红素血症和光疗对新生儿凋亡微粒水平的影响。

IF 1.2 4区医学

Blood Coagulation & Fibrinolysis Pub Date : 2024-07-01 Epub Date: 2024-05-10 DOI: 10.1097/MBC.0000000000001297

Ebru Yücesoy, Fatma Demir Yenigürbüz, Halil Ateş, Funda Tüzün, Nuray Duman, Hasan Özkan, Hale Ören

{"title":"Effect of hyperbilirubinemia and phototherapy on apoptotic microparticle levels in neonates.","authors":"Ebru Yücesoy, Fatma Demir Yenigürbüz, Halil Ateş, Funda Tüzün, Nuray Duman, Hasan Özkan, Hale Ören","doi":"10.1097/MBC.0000000000001297","DOIUrl":"https://doi.org/10.1097/MBC.0000000000001297","url":null,"abstract":"Objective: We aimed to evaluate the effect of hyperbilirubinemia and phototherapy on total apoptotic, platelet-derived, endothelial-derived, and tissue factor (TF)-positive apoptotic microparticle (MP) levels in neonates with nonhemolytic pathologic hyperbilirubinemia.Methods: Thirty-three term neonates with nonhemolytic pathologic hyperbilirubinemia and 25 healthy term neonates were included. MP levels were analyzed by flow cytometry using peripheral blood samples only once for the neonates in the control group and twice for the neonates in the study group (before and after phototherapy). Annexin V-positive MPs were defined as apoptotic MPs. Platelet-derived MPs were defined as those containing CD31. MPs containing CD144 were defined as endothelial-derived MPs, and MPs expressing TF were identified as those containing CD142.Results: The rates of total apoptotic and endothelial-derived apoptotic MPs were significantly higher in the study group than the control group before phototherapy (P = 0.012 and P = 0.003, respectively) and after phototherapy (P = 0.046 and P = 0.001, respectively). Total apoptotic, platelet-derived, endothelial-derived, and TF-positive apoptotic MPs did not show any significant differences before and after phototherapy in the study group (P = 0.908, P = 0.823, P = 0.748, and P = 0.437, respectively).Conclusions: Our study demonstrated that total apoptotic and endothelial-derived apoptotic MPs are increased in cases of nonhemolytic pathologic hyperbilirubinemia. We showed that phototherapy does not have a significant effect on apoptotic MP levels. Further studies are needed to evaluate the risk of elevated apoptotic MPs on the development of thromboembolism in neonates with nonhemolytic pathologic hyperbilirubinemia.","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554160","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

The impact of von Willebrand factor on fibrin formation and structure unveiled with type 3 von Willebrand disease plasma. 用 3 型 von Willebrand 病血浆揭示 von Willebrand 因子对纤维蛋白形成和结构的影响。

IF 1.2 4区医学

Blood Coagulation & Fibrinolysis Pub Date : 2024-07-01 Epub Date: 2024-05-20 DOI: 10.1097/MBC.0000000000001309

Marina Martinez-Vargas, Justin Courson, Luis Gardea, Mehmet Sen, Andrew Yee, Rolando Rumbaut, Miguel A Cruz

{"title":"The impact of von Willebrand factor on fibrin formation and structure unveiled with type 3 von Willebrand disease plasma.","authors":"Marina Martinez-Vargas, Justin Courson, Luis Gardea, Mehmet Sen, Andrew Yee, Rolando Rumbaut, Miguel A Cruz","doi":"10.1097/MBC.0000000000001309","DOIUrl":"10.1097/MBC.0000000000001309","url":null,"abstract":"Normally, von Willebrand factor (VWF) remains inactive unless its A1A2 domains undergo a shear stress-triggered conformational change. We demonstrated the capacity of a recombinant A2 domain of VWF to bind and to affect fibrin formation, altering the fibrin clot structure. The data indicated that VWF contains an additional binding site for fibrin in the A2 domain that plays a role in the incorporation of VWF to the polymerizing fibrin. This study is to examine the hypothesis that active plasma VWF directly influence fibrin polymerization and the structure of fibrin clots. The study used healthy and type 3 von Willebrand disease (VWD) plasma, purified plasma VWF, fibrin polymerization assays, confocal microscopy and scanning electron microscopy. The exposed A2 domain in active VWF harbors additional binding sites for fibrinogen, and significantly potentiates fibrin formation (P < 0.02). Antibody against the A2 domain of VWF significantly decreased the initial rate of change of fibrin formation (P < 0.002). Clot analyses revealed a significant difference in porosity between normal and type 3 VWD plasma (P < 0.008), further supported by scanning electron microscopy, which demonstrated thicker fibrin fibers in the presence of plasma VWF (P < 0.0003). Confocal immunofluorescence microscopy showed punctate VWF staining along fibrin fibrils, providing visual evidence of the integration of plasma VWF into the fibrin matrix. The study with type 3 VWD plasma supports the hypothesis that plasma VWF directly influences fibrin polymerization and clot structure. In addition, a conformational change in the A1A2 domains exposes a hidden fibrin(ogen) binding site, indicating that plasma VWF determines the fibrin clot structure.","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Characterization of zebrafish coagulation cofactors Fviii and Fv mutants and modeling hemophilia A and factor V deficiency. 斑马鱼凝血辅因子 Fviii 和 Fv 突变体的特征以及 A 型血友病和 V 型因子缺乏症的建模。

IF 1.2 4区医学

Blood Coagulation & Fibrinolysis Pub Date : 2024-07-01 Epub Date: 2024-06-10 DOI: 10.1097/MBC.0000000000001308

Sanchi Dhinoja, Anthony De Maria, Ayah Al Qaryoute, Pudur Jagadeeswaran

{"title":"Characterization of zebrafish coagulation cofactors Fviii and Fv mutants and modeling hemophilia A and factor V deficiency.","authors":"Sanchi Dhinoja, Anthony De Maria, Ayah Al Qaryoute, Pudur Jagadeeswaran","doi":"10.1097/MBC.0000000000001308","DOIUrl":"10.1097/MBC.0000000000001308","url":null,"abstract":"The aim of this study is to characterize zebrafish coagulation cofactors fviii and fv mutant fish and assess if they phenocopy classical hemophilia A and factor V deficiency in humans. The embryos from fviii and fv zebrafish heterozygote mutants generated by ENU mutagenesis were purchased from the ZIRC repository. They were reared to adulthood and genotyped. The heterozygote male and female were crossed to get homozygote, heterozygote, and wild-type fish. Functional kinetic coagulation assays and bleeding assays were performed on normal and mutant adult fish, and venous laser injury assays were performed on the larvae. The DNA from fviii and fv mutants were sequenced to confirm if they have a premature stop codon in exon 19, and in exon 2, respectively, and in both mutants, the amino acid glutamine is replaced with a stop codon. Homozygous and heterozygous 5 days post fertilization (dpf) larvae for fviii and fv deficient mutants exhibited prolonged time to occlusion after venous laser injury compared to wild-type controls. The homozygous and heterozygous fviii adult mutants showed modest bleeding and delayed fibrin formation in the kinetic partial thromboplastin time (kPTT) assay with their plasma. fv homozygous larvae had poor survival beyond 12 dpf. However, heterozygous fv mutants exhibited heavy bleeding and prolonged fibrin formation in the kPTT and kPT assay compared with wild-type siblings. Our characterization showed fviii and fv mutants from ZIRC phenocopied to a considerable extent classical hemophilia A and factor V deficiency in humans, respectively. These models should be useful in studying and developing novel drugs that reverse the phenotype and in generating suppressor mutations to identify novel factors that compensate for these deficiencies.","PeriodicalId":8992,"journal":{"name":"Blood Coagulation & Fibrinolysis","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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