Severe thrombophilia in a factor V‐deficient patient homozygous for the Ala2086Asp mutation (FV Besançon)
| Autor: | Marie-Christine Alessi, Jan Rosing, Guillaume Mourey, Pierre-Emmanuel Morange, Marjorie Poggi, Elisabetta Castoldi, M. Christella L. G. D. Thomassen, Tilman M. Hackeng, Manal Ibrahim-Kosta, Alexandra Fournel, Catherine P.M. Hayward, Nathalie Hezard, Kanin Wichapong |
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| Přispěvatelé: | Hôpital de la Timone [CHU - APHM] (TIMONE), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Department of Biochemistry, Maastricht University [Maastricht], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Canadian Institutes of Health Research (CIHR)MOP 133474, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Biochemie, RS: Carim - B01 Blood proteins & engineering, RS: Carim - B03 Cell biochemistry of thrombosis and haemostasis |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
factor V deficiency
Factor V Deficiency compared with normal FVa has both pro- and anticoagulant functions. Objective We investigated an FV-deficient patient (FV:C 3% 030204 cardiovascular system & hematology Thrombophilia but also a lower rate of APC-catalyzed inactivation in the presence of protein S. Conclusions FVBesancon induces a hypercoagulable state via quantitative (markedly decreased FV level) and qualitative (phospholipid-binding defect) effects that affect anticoagulant pathways (anticoagulant activities of FV Background Coagulation factor V (FV) 03 medical and health sciences 0302 clinical medicine Tissue factor pathway inhibitor [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Prothrombinase V-max) of prothrombin activation medicine FVa inactivation Humans predicting impaired binding of FV(a) to phospholipids. Recombinant FVBesancon was hardly secreted Platelet phospholipids indicating that this mutation is responsible for the patient's FV deficiency. Model system experiments performed using highly diluted plasma as a source of FV showed that FVa(Besancon) has slightly (<= 1.5-fold) unfavorable kinetic parameters (K-m biology Chemistry Homozygote present in plasma and platelets Factor V Hematology medicine.disease Molecular biology Mutation biology.protein activated protein C resistance tissue factor pathway inhibitor alpha level) more strongly than the prothrombinase activity of FVa. A possible specific role of platelet FV cannot be excluded venous thrombosis Blood Coagulation Tests Activated protein C resistance thrombin generation in the patient's platelet-rich plasma (PRP) was higher than in control PRP and extremely resistant to activated protein C (APC). This was partially attributable to the complete abolition of the APC-cofactor activity of FV and a marked reduction of plasma tissue factor pathway inhibitor antigen and activity. The patient was homozygous for a novel missense mutation (Ala2086Asp Protein C FV:Ag 4%) paradoxically presenting with recurrent venous thrombosis (11 events) instead of bleeding. Methods/Results Thrombophilia screening revealed only heterozygosity for the F2 20210G>A mutation. Although thrombin generation in the patient's platelet-poor plasma was suggestive of a hypocoagulable state medicine.drug |
| Zdroj: | Journal of Thrombosis and Haemostasis Journal of Thrombosis and Haemostasis, 2021, 19 (5), pp.1186-1199. ⟨10.1111/jth.15274⟩ Journal of Thrombosis and Haemostasis, Wiley, 2021, 19 (5), pp.1186-1199. ⟨10.1111/jth.15274⟩ Journal of Thrombosis and Haemostasis, 19(5), 1186-1199. Wiley |
| ISSN: | 1538-7933 1538-7836 |
| DOI: | 10.1111/jth.15274⟩ |
| Popis: | International audience; Background Coagulation factor V (FV), present in plasma and platelets, has both pro- and anticoagulant functions.Objective We investigated an FV-deficient patient (FV:C 3%, FV:Ag 4%) paradoxically presenting with recurrent venous thrombosis (11 events) instead of bleeding.Methods/Results Thrombophilia screening revealed only heterozygosity for the F2 20210G>A mutation. Although thrombin generation in the patient's platelet-poor plasma was suggestive of a hypocoagulable state, thrombin generation in the patient's platelet-rich plasma (PRP) was higher than in control PRP and extremely resistant to activated protein C (APC). This was partially attributable to the complete abolition of the APC-cofactor activity of FV and a marked reduction of plasma tissue factor pathway inhibitor antigen and activity. The patient was homozygous for a novel missense mutation (Ala2086Asp, FVBesancon) that favors a "closed conformation" of the C2 domain, predicting impaired binding of FV(a) to phospholipids. Recombinant FVBesancon was hardly secreted, indicating that this mutation is responsible for the patient's FV deficiency. Model system experiments performed using highly diluted plasma as a source of FV showed that, compared with normal FVa, FVa(Besancon) has slightly ( |
| Databáze: | OpenAIRE |
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