In vitro and ex vivo rescue of a nonsense mutation responsible for severe coagulation factor V deficiency.

Background: Coagulation factor V (FV) deficiency is a rare bleeding disorder that is usually managed with fresh-frozen plasma. Patients with nonsense mutations may respond to treatment with readthrough agents.

Objectives: To investigate whether the F5 p.

Whole-Exome Sequencing in a Family with an Unexplained Tendency for Venous Thromboembolism: Multicomponent Prediction of Low-Frequency Variant Deleteriousness and of Individual Protein Interaction.

Whole-exome sequencing (WES) in families with an unexplained tendency for venous thromboembolism (VTE) may favor detection of low-frequency variants in genes with known contribution to hemostasis or associated with VTE-related phenotypes. WES analysis in six family members, three of whom affected by documented VTE, filtered for MAF < 0.04 in 192 candidate genes, revealed 22 heterozygous (16 missense and six synonymous) variants in patients.

Modulation of factor VIII pharmacokinetics by genetic components in factor VIII receptors.

Introduction: Gene variation in receptors for circulating factor VIII (FVIII) is candidate to explain the large inter-patient variability of infused FVIII pharmacokinetics (PK) in haemophilia A (HA).

Aim: To compare in an Italian HA cohort (n = 26) the influence on FVIII PK of genetic components in four von Willebrand factor (VWF)/FVIII receptors.

Methods: Genotypes of low-density lipoprotein receptor (LDLR), asialoglycoprotein receptor minor subunit (ASGR2), family 4 member M (CLEC4M), stabilin2 (STAB2) and ABO blood-group, and VWF:Ag levels were included as independent variables in linear regression analyses of two-compartment model (TCM) - standard half-life (SHL) FVIII PK parameters.

The p.P1127S pathogenic variant lowers von Willebrand factor levels through higher affinity for the macrophagic scavenger receptor LRP1: Clinical phenotype and pathogenic mechanisms.

Background: The index case is a 21-year-old Italian woman with a mild hemorrhagic syndrome and von Willebrand factor antigen (VWF:Ag) = 34.3 U/dl, VWF recombinant glycoprotein Ib (VWF:GpIbR) = 32.8 U/dl, and factor VIII (FVIII) = 55.

Combination of rs868875 G-Carriership and O Genotypes May Predict Faster Decay of FVIII Infused in Hemophilia A Patients.

The C-type lectin CLEC4M binds and internalizes factor VIII (FVIII). Common variants have been associated with FVIII pharmacokinetic (PK) profiles in hemophilia A (HA) patients. The two-compartment PK analysis of plasma-derived (pd-) and full length recombinant FVIII concentrates was conducted in twenty-six patients (FVIII:C ≤ 2 IU/dL).