0000000000986229

AUTHOR

Barbara Lunghi

showing 2 related works from this author

VITAMIN K-INDUCED MODIFICATION OF COAGULATION PHENOTYPE IN VKORC1 HOMOZYGOUS DEFICIENCY

2008

Summary.  Background: Combined vitamin K-dependent clotting factor (VKCF) deficiency type 2 (VKCFD2) is a rare bleeding disorder caused by mutated vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) gene. Methods and results: An Italian patient with moderate to severe bleeding tendency was genotyped, and found to be homozygous for the unique VKORC1 mutation (Arg98Trp) so far detected in VKCFD2. The activity levels of VKCFs were differentially reduced, and inversely related to the previously estimated affinity of procoagulant factor propeptides for the γ-carboxylase. The normal (factor IX) or reduced antigen levels (other VKCFs) produced a gradient in specific activities. Vitamin K su…

Adultmedicine.medical_specialtycoagulation factor levelsVitamin KProtein SMixed Function OxygenasesTissue factorchemistry.chemical_compoundInternal medicineVitamin K Epoxide ReductasesmedicineVKCFD2HumansFactor IXClotting factorCoagulation factor levels; Thrombin generation; Vitamin K supplementation; VKCFD2; VKORC1 mutation;biologyFactor VIIChemistryFactor XHomozygotevitamin K supplementationHematologyBlood Coagulation DisordersEndocrinologyTreatment OutcomeCoagulationthrombin generationImmunologyMutationbiology.proteinFemaleBlood Coagulation TestsVKCFD2 VKORC1 mutation coagulation factor levels thrombin generation vitamin K supplementationProtein Cmedicine.drugHalf-LifeVKORC1 mutation
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F9 missense mutations impairing factor IX activation are associated with pleiotropic plasma phenotypes.

2022

Background Circulating dysfunctional factor IX (FIX) might modulate distribution of infused FIX in hemophilia B (HB) patients. Recurrent substitutions at FIX activation sites (R191-R226, >300 patients) are associated with variable FIX activity and antigen (FIXag) levels. Objectives To investigate the (1) expression of a complete panel of missense mutations at FIX activation sites and (2) contribution of F9 genotypes on the FIX pharmacokinetics (PK). Methods We checked FIX activity and antigen and activity assays in plasma and after recombinant expression of FIX variants and performed an analysis of infused FIX PK parameters in patients (n = 30), mostly enrolled in the F9 Genotype and PK HB …

medicine.medical_specialtypharmacogenetics.Mutation MissenseSocio-culturaleAlpha (ethology)aemophilia Brecombinant proteinsHemophilia Blaw.inventionFactor IXAntigenlawInternal medicineGenotypemedicineMissense mutationHumansHaemophilia BpharmacokineticBeta (finance)Factor IXpharmacogeneticsChemistryHematologymedicine.diseaseEndocrinologyPhenotypefactor IX activation; hemophilia B; pharmacogenetics; pharmacokinetics; recombinant proteinsRecombinant DNAFemalefactor IX activationBlood Coagulation Testspharmacokineticsrecombinant proteinmedicine.drugJournal of thrombosis and haemostasis : JTH
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