Assessing Clinically Meaningful Hypercoagulability after COVID-19 Vaccination: A Longitudinal Study.

A large number of daily requests to exclude possible prothrombotic risk factors for coronavirus disease 2019 (COVID-19) vaccines were received. Our aim was to longitudinally evaluate coagulation profiles in a series of healthy subjects who received COVID-19 vaccination and assess hypercoagulability thereafter. Volunteers awaiting a first or second dose of either the ChAdOx1 or BNT162b2 vaccine were enrolled.

Absence of hypercoagulability after nCoV-19 vaccination: An observational pilot study.

Background: It is still unknown whether COVID-19 vaccines induce a prothrombotic state or increase the hypercoagulable condition in subjects with a predisposition to thrombosis.

Objectives: We evaluated the coagulation profile in a series of healthy subjects who received the first dose of the BNT162b2 or the ChAdOx1 vaccines and assessed whether hypercoagulability developed.

Patients/methods: Volunteers among the staff of the University of Padua or health care professionals in the Padua University Hospital who had received either the ChAdOx1 or BNT162b2 vaccine in the previous 10 ± 2 days were eligible.

Partial F8 gene duplication (factor VIII Padua) associated with high factor VIII levels and familial thrombophilia.

High coagulation factor VIII (FVIII) levels comprise a common risk factor for venous thromboembolism (VTE), but the underlying genetic determinants are largely unknown. We investigated the molecular bases of high FVIII levels in 2 Italian families with severe thrombophilia. The proband of the first family had a history of recurrent VTE before age 50 years, with extremely and persistently elevated FVIII antigen and activity levels (>400%) as the only thrombophilic defects.

Thromboelastometry hypercoagulable profiles and portal vein thrombosis in cirrhotic patients with hepatocellular carcinoma.

Background: Cirrhotic patients with hepatocellular carcinoma (HCC) exhibit hypercoagulability.

Aim: We investigated whether thromboelastometry can detect hypercoagulability in these patients and the association with portal vein thrombosis (PVT).

Methods: At baseline, cirrhotic patients with and without HCC underwent thromboelastometry.

Endocytosis of exogenous factor V by ex-vivo differentiated megakaryocytes from patients with severe parahaemophilia.

Although human megakaryocytes can synthesize factor V (FV), platelet FV derives largely from endocytosis of plasma FV. Recently, it has been shown that plasma transfusions can replenish the platelet FV pool in parahaemophilic patients. Here we corroborate this finding by showing FV endocytosis by ex vivo differentiated megakaryocytes derived from patients with inherited parahaemophilia.

Higher and lower active circulating VWF levels: different facets of von Willebrand disease.

Most circulating von Willebrand factor (VWF) is normally inactive and incapable of binding platelets, but numerous disorders may modify the proportion of active VWF. We explored active VWF levels in patients with von Willebrand disease (VWD) whose VWF had a higher affinity for platelet glycoprotein (GP)Ib, but different susceptibilities to ADAMTS13 and multimer patterns (9 patients lacking large multimers, 10 with a normal pattern); 12 patients with VWF C2362F and R1819_C1948delinsS mutations, which make VWF resistant to ADAMTS13 were also studied. Type 2B patients with abnormal or normal multimers had significantly more active VWF (3·33 ± 1·6 and 3·74 ± 0·74, respectively; normal 0·99 ± 0·23).

Type 1 von Willebrand disease due to reduced von Willebrand factor synthesis and/or survival: observations from a case series.

It may be difficult to diagnose type 1 von Willebrand disease (VWD) because of its heterogeneous and sometimes elusive nature. To evaluate the contribution of a shorter von Willebrand factor (VWF) survival in modulating VWD phenotype, the VWF half-life was assessed in 45 type 1 VWD patients using a 24-h 1-desamino-8-d-arginine vasopressin (DDAVP) test. A shorter VWF survival was observed in patients with C1130F mutations (T(1/2) elimination [T(1/2)el]=4.

Microsatellite (GT)(n) repeats and SNPs in the von Willebrand factor gene promoter do not influence circulating von Willebrand factor levels under normal conditions.

Von Willebrand factor (VWF) levels vary considerably in normal individuals, influenced by inherited and acquired modulators. ABO blood group is the major inherited determinant of VWF levels, but a role has also been attributed to the VWF gene promoter, haplotype 1 (-3268G/-2709C/-2661A/-2527G) being associated with higher VWF levels than haplotype 2 (-3268C/-2709T/-2661G/-2527A), and the polymorphic locus (GT)(n) modulating the shear stress-induced activation of the VWF promoter. We characterized the (GT)(n) of the VWF promoter in 394 healthy individuals and assessed whether its variable length influenced VWF levels in normal conditions.

A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor.

ABO blood groups greatly influence circulating von Willebrand factor (VWF) levels, and O group subjects have lower VWF values. In this study, we investigated whether ABO groups affect VWF survival by monitoring the post-DDAVP (1-desamino-8-d arginine vasopressin) time courses of VWF antigen (VWF:Ag), VWF collagen binding (VWF:CB), and factor VIII (FVIII) in 47 healthy subjects (28 O and 19 non-O blood groups). The elimination half-life (T1/2el) of VWF was found significantly shorter in O than in non-O subjects (10.

Polymorphisms in von Willebrand factor gene promoter influence the glucocorticoid-induced increase in von Willebrand factor: the lesson learned from Cushing syndrome.

Cushing syndrome (CS) features high-glucocorticoid secretion and an associated hypercoagulable state often involving an increase in von Willebrand factor (VWF). To identify any influence of VWF promoter on glucocorticoid haemostatic effects, four polymorphic positions (-3267, -2708, -2659 and -2525) segregating as haplotypes 1 (GCAG) or 2 (CTGA) were analysed in 50 CS patients with high VWF (group I) and normal VWF (group II) levels, divided by ABO group. Genotype distribution differed significantly between the two groups: in group I, 25.

A novel von Willebrand factor mutation (I1372S) associated with type 2B-like von Willebrand disease: an elusive phenotype and a difficult diagnosis.

Mutations in the A1 domain of von Willebrand factor (VWF) may be associated with gain of function in the VWF-platelet GPIb interaction and consumption of large VWF multimers, as seen in type 2B von Willebrand disease (VWD). We report a new VWF abnormality associated with greater VWF-GPIb interaction in the presence of all VWF multimers. The index case is a woman with a lifelong history of bleeding, found hyperresponsive to ristocetin with spontaneous platelet aggregation (SPA).

Combined partial exon skipping and cryptic splice site activation as a new molecular mechanism for recessive type 1 von Willebrand disease.

We describe the complex picture associated with a mutated splice junction in intron 13 of von Willebrand factor (VWF) gene. The proband, characterized by a marked decrease in plasma and platelet VWF and near normal multimer organization, was classified as recessive type 1 von Willebrand disease (VWD). Genetic analysis demonstrated that he was homozygous for the 1534-3C > A mutation in the consensus sequence of the acceptor splicing site of intron 13 of the VWF gene.

Identifying type Vicenza von Willebrand disease.

Increased clearance of von Willebrand factor (VWF) is one of the main features of type Vicenza von Willebrand disease (VWD), a variant with plasma and platelet VWF level discrepancies and unusually large VWF multimers. Diagnosing type Vicenza VWD may not be easy, due to its heterogeneous phenotype. Here we describe the criteria we adopted to identify type Vicenza in a large group of VWD patients.

A new L1446P mutation is responsible for impaired von Willebrand factor synthesis, structure, and function.

We report on a new mutation (4337T-->C) in exon 28 of the von Willebrand factor (VWF) gene, resulting in a substitution of L with P at residue 1446 (L1446P) of pre-pro-VWF. The defect is transmitted as a dominant trait and induces a reduced VWF synthesis, an abnormal VWF multimer pattern and a deficient VWF-platelet glycoprotein Ib interaction. The proband had low plasma and platelet VWF antigen levels, a reduced VWF collagen-binding capacity, and a disproportionately low VWF ristocetin cofactor activity, associated with the absence of ristocetin-induced platelet aggregation.

An Arg760Cys mutation in the consensus sequence of the von Willebrand factor propeptide cleavage site is responsible for a new von Willebrand disease variant.

We describe a von Willebrand disease (VWD) variant characterized by the persistence of von Willebrand factor (VWF) propeptide as a result of a C>T transition at nucleotide 2527 in exon 17 of the VWF gene. This mutation, which was present in the proband and his father, predicts the substitution of Cys for Arg at position 760 of pre-pro-VWF, 4 residues before the propeptide cleavage site belonging to a consensus sequence for substrate recognition by the processing enzyme paired dibasic amino acid-cleaving enzyme (PACE)/furin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) documented the presence of both processed and unprocessed VWF in the patient's plasma, with unprocessed VWF relatively less represented.

Reduced von Willebrand factor survival in type Vicenza von Willebrand disease.

Type Vicenza variant of von Willebrand disease (VWD) is characterized by a low plasma von Willebrand factor (VWF) level and supranormal VWF multimers. Two candidate mutations, G2470A and G3864A at exons 17 and 27, respectively, of the VWF gene were recently reported to be present in this disorder. Four additional families, originating from northeast Italy, with both mutations of type Vicenza VWD are now described.