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Factor VII (FVII) is a vitamin K-dependent glycoprotein which, in its activated form (FVIIa), participates in the coagulation process by activating factor X and factor IX. FVII is secreted as single peptide chain of 406 residues. Plasma-derived FVII undergoes many post-translational modifications such as gamma-carboxylation, N- and O-glycosylation, beta-hydroxylation. Despite glycosylation of recombinant FVIIa has been fully characterized, nothing is reported on the N- and O-glycans of plasma-derived FVII (pd-FVII) and on their structural heterogeneity at each glycosylation site. N- and O-glycosylation sites and site specific heterogeneity of pd-FVII were studied by various complementary qualitative and quantitative techniques. A MALDI-MS analysis of the native protein indicated that FVII is a 50.1 kDa glycoprotein modified on two sites by diantennary, disialylated non-fucosylated (A2S2) glycans. LC-ESIMS/MS analysis revealed that both light chain and heavy chain were N-glycosylated mainly by A2S2 but also by triantennary sialylated glycans. Nevertheless, lower amounts of triantennary structures were found on Asn(322) compared to Asn(145). Moreover, the triantennary glycans were shown to be fucosylated. In parallel, quantitative analysis of the isolated glycans by capillary electrophoresis indicated that the diantennary structures represented about 50% of the total glycan content. Glycan sequencing using different glycanases led to the identification of triantennary difucosylated structures. Last, MS and MS/MS analysis revealed that FVII is O-glycosylated on the light chain at position Ser(60) and Ser(52) which are modified by oligosaccharide structures such as fucose and Glc(Xyl)(0-1-2), respectively. These latter three O-glycans coexist in equal amounts in plasma-derived FVII.
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http://dx.doi.org/10.1007/s10719-008-9143-7 | DOI Listing |
Rev Med Chil
January 2024
Hospital Clínico Universidad de Chile, Santiago, Chile.
Tissue Factor-Factor VII complex is essential in coagulation activation. Congenital factor VII deficiency is a rare disorder that has an autosomal recessive inheritance. Clinical presentations are heterogeneous, ranging from asymptomatic carriers to severe bleeding phenotypes with factor VII replacement therapy requirements.
View Article and Find Full Text PDFTurk J Pediatr
August 2021
Division of Pediatric Hematology, Department of Pediatric, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.
Background And Objectives: In this retrospective report the aim was to present the experience about bleeding characteristics and management of minor surgeries in rare bleeding disorders (RBDs).
Methods: Twenty-six patients were included; with Factor (F) V, FV+VIII, VII, FXI deficiency and afibrinogenemia. Six of the patients were asymptomatic.
Acta Haematol
June 2021
Department of Hematology and Oncology, Nagano Children's Hospital, Azumino, Japan,
Treating patients with hemophilia and inhibitors is often problematic. The presence of inhibitors negatively impacts the effectiveness of treatment to achieve hemostasis especially in patients with hemophilia B, owing mainly to allergic reactions to factor IX (FIX) concentrates and the low success rate of immune tolerance therapy. A 9-month-old boy had intracranial hemorrhage and was diagnosed with hemophilia B.
View Article and Find Full Text PDFTurk Pediatri Ars
June 2020
Division of Pediatric Hematology and Oncology, İstanbul University Oncology Institute, İstanbul Turkey.
Aim: Factor VII deficiency is one of the hereditary coagulation disorders that has autosomal reccessive inheritance and is observed relatively frequently (1/500 000). It is clinically heterogeneous, and may be asymptomatic or lead to life-threatening bleeding. Thus, there is no correlation between FVII activity and clinical findings.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!