Von Willebrand disease type 2B with a novel mutation in the VWF gene.

We report a 38-year-old woman who presented with a subdural hematoma after minor facial trauma in a stressful situation. The laboratory data showed a subnormal platelet count (166×10/L), VWF:RCo activity was 45% and VWF:Ag was 53% with a VWF:RCo/VWF Ag ratio of 0.79.

Arterial Pulsatility and Circulating von Willebrand Factor in Patients on Mechanical Circulatory Support.

Background: The main risk factor for bleeding in patients with continuous-flow mechanical circulatory support (CF-MCS) is the acquired von Willebrand factor (VWF) defect related to the high shear-stress forces developed by these devices. Although a higher bleeding rate has been reported in CF-MCS recipients who had reduced pulsatility, the relation between pulsatility and the VWF defect has never been studied.

Objectives: The purpose of this study was to investigate the relation between pulsatility and VWF under CF-MCS.

A novel platelet-type von Willebrand disease mutation (GP1BA p.Met255Ile) associated with type 2B "Malmö/New York" von Willebrand disease.

Interaction between von Willebrand factor (VWF) and platelet GPIbα is required for primary haemostasis. Lack or loss-of-function in the ligand-receptor pair results in bleeding complications. Paradoxically, gain-of-function mutations in VWF or GPIbα also result in bleeding complications as observed in type 2B von Willebrand disease (VWD) and platelet-type- (PT-) VWD, respectively.

Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement.

Background: Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR.

Methods: We enrolled 183 patients undergoing TAVR.

A Laboratory Phenotype/Genotype Correlation of 1167 French Patients From 670 Families With von Willebrand Disease: A New Epidemiologic Picture.

von Willebrand disease (VWD) is a genetic bleeding disease due to a defect of von Willebrand factor (VWF), a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels <50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50 IU/dL).

A novel ELISA-based diagnosis of acquired von Willebrand disease with increased VWF proteolysis.

Von Willebrand disease-type 2A (VWD-2A) and acquired von Willebrand syndrome (AVWS) due to aortic stenosis (AS) or left ventricular assist device (LVAD) are associated with an increased proteolysis of von Willebrand factor (VWF). Analysis of VWF multimeric profile is the most sensitive way to assess such increased VWF-proteolysis. However, several technical aspects hamper a large diffusion among routine diagnosis laboratories.

Von Willebrand factor as a biological sensor of blood flow to monitor percutaneous aortic valve interventions.

Rationale: Percutaneous aortic valve procedures are a major breakthrough in the management of patients with aortic stenosis. Residual gradient and residual aortic regurgitation are major predictors of midterm and long-term outcome after percutaneous aortic valve procedures. We hypothesized that (1) induction/recovery of high molecular weight (HMW) multimers of von Willebrand factor defect could be instantaneous after acute changes in blood flow, (2) a bedside point-of-care assay (platelet function analyzer-closure time adenine DI-phosphate [PFA-CADP]), reflecting HMW multimers changes, could be used to monitor in real-time percutaneous aortic valve procedures.

Von Willebrand factor, a versatile player in gastrointestinal bleeding in left ventricular assist device recipients?

Background: Bleeding originating in the gastrointestinal (GI) tract is one of the most common adverse events after left ventricular assist device (LVAD) implantation. In these patients, GI bleeding appears to be the consequence of altered hemostasis on the one hand and alterations of the GI microvasculature on the other.

Case Report: We report the case of a patient who suffered repeated, severe GI bleeding early after implantation of a HeartMate II continuous-flow LVAD.

Persistence of circulating ADAMTS13-specific immune complexes in patients with acquired thrombotic thrombocytopenic purpura.

Anti-ADAMTS13 autoantibodies are the main cause of acquired thrombotic thrombocytopenic purpura. Binding of these antibodies to ADAMTS13 eventually results in the formation of antigen-antibody immune complexes. Circulating ADAMTS13-specific immune complexes have been described in patients with acquired thrombotic thrombocytopenic purpura, although the prevalence and persistence of these immune complexes over time have hitherto remained elusive.

Mutations in the A3 domain of von Willebrand factor inducing combined qualitative and quantitative defects in the protein.

Two unrelated families were recruited in the French Reference Center for von Willebrand Disease with moderate bleeding symptoms associated with low von Willebrand factor (VWF) antigen levels, decreased collagen binding assay, and no or partial response to desmopressin. Genetic analysis showed the presence of heterozygous mutations in the A3 domain away from the collagen-binding surface: 1 never reported previously (p.L1696R) and another (p.

Clinical and prognostic implications of low or high level of von Willebrand factor in patients with Waldenstrom macroglobulinemia.

Acquired von Willebrand syndrome is described in patients with Waldenström macroglobulinemia (WM). Assessment of ristocetin cofactor activity (VWF:RCo) and von Willebrand factor (VWF) antigen (VWF:Ag) in 72 consecutive patients with WM showed a negative relation between VWF levels < 130 U/dL and both monoclonal immunoglobulin M concentration (mIgMC) and viscosity. Ten patients with VWF:RCo < 50 U/dL (< 40 for patients with blood group O) fulfilled the acquired von Willebrand syndrome criteria.

Evaluation of an automated von Willebrand factor activity assay in von Willebrand disease.

We evaluated the use of the turbidimetric HemosIL von Willebrand Factor (VWF) Activity assay (VWF:Act) on the STA-R automated coagulometer (Stago, Asnières, France) for the diagnosis of von Willebrand disease (VWD). For this, we prospectively screened 268 patients. As a second part, we retrospectively assayed 111 patients with well-defined VWD subtype.

Diluted Russell viper-venom time improves identification of antiphospholipid syndrome in a lupus anticoagulant-positive patient population.

The objective of this retrospective study was to evaluate the potential ability of diluted Russell viper-venom time (dRVVT) to identify antiphospholipid syndrome (APS) in a lupus anticoagulant (LA)-positive patient population, already selected by other LA clotting tests. Our cohort of positive LA patients was first identified in our outpatients population by the following sensitive LA-detecting tests: Rosner index, diluted prothrombin time (dPT) and Rosove index. Then the 227 consecutive LA-positive patients were tested for dRVVT with the same blood sample.

Functional impairment of von Willebrand factor in hypertrophic cardiomyopathy: relation to rest and exercise obstruction.

Background: Hypertrophic obstructive cardiomyopathy submits blood to conditions of high shear stress. High shear stress impairs von Willebrand factor (VWF) and promotes abnormal bleeding in aortic stenosis. We sought to evaluate VWF impairment and its relationships to baseline or exercise obstruction in hypertrophic cardiomyopathy (HCM).

Type 2N von Willebrand disease due to compound heterozygosity for R854Q and a novel R763G mutation at the cleavage site of von Willebrand factor propeptide.

Type 2N von Willebrand disease (VWD) is characterized by a markedly decreased affinity of von Willebrand factor (VWF) for factorVIII (FVIII) and is caused by mutations in the D' or D3 domain of mature VWF. We now report a French patient with an atypical 2N VWD phenotype associating FVIII deficiency with plasmaVWF unable to bind FVIII (undetectableVWF:FVIIIB) but with an abnormal multimeric profile. This patient is heterozygous for both the frequent R854Q type 2NVWD mutation and a novel R763G mutation at the cleavage site between VWF propeptide and mature VWF.

Significance of persistent antiphospholipid antibodies in the elderly.

Objective: The prevalence of anticardiolipin antibodies (aCL) and of vascular diseases increases with age, and aCL may be associated with various diseases in the elderly. So the significance of aCL in the elderly remains difficult to determine. We sought to determine the significance of persistent antiphospholipid antibodies (aPL) in the elderly.

Measurement of von Willebrand factor binding to a recombinant fragment of glycoprotein Ibalpha in an enzyme-linked immunosorbent assay-based method: performances in patients with type 2B von Willebrand disease.

Type 2B von Willebrand disease (VWD) is characterised by an increased affinity of von Willebrand factor (VWF) for its platelet receptor glycoprotein Ib (GPIb). This feature is usually studied in vitro by a ristocetin-dependent VWF platelet-binding assay, which has some limitations as it requires [e.g.

Thrombotic thrombocytopenic purpura: medical and biological monitoring of six pregnancies.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare cause of severe thrombocytopenia in pregnancy.

Methods: Six pregnancies in five patients with TTP were followed prospectively over 5 years. Ultralarge von Willebrand factor (ULvWF) multimers and cleaving protease (cp) levels were measured.

Standardization of factor VII/activated factor VII measurement in plasma of patients treated with recombinant factor activated VII.

To improve the standardization of the factor VII clotting activity (FVII:C) assay in patients treated with recombinant activated factor VII (rFVIIa), we conducted a multicentre study on plasma samples from four patients with haemophilia A, before and at various times after injection of a single dose of rFVIIa. FVII:C and prothrombin time were measured with the methods and reagents routinely used in each laboratory. Strong inter-laboratory variability of FVII:C values was found.

Reassessment of von Willebrand factor (VWF), VWF propeptide, factor VIII:C and plasminogen activator inhibitors 1 and 2 during normal pregnancy.

The use of von Willebrand factor [VWF antigen (WF:Ag)] measurement as a marker of endothelial cell activation for monitoring hypertensive pregnancies is limited by the poor definition of reference values. We reassessed these reference values using different assays, and those of the propeptide (VWF:Ag II) and factor VIII coagulant activity (factor VIII:C), in a large population of normal pregnancies, at 3-week intervals of gestational age. Plasminogen activator inhibitors (PAI-1 and PAI-2) were measured in parallel.

Large experience with a factor VIII binding assay of plasma von Willebrand factor using commercial reagents.

The present diagnostic assay for type 2N von Willebrand disease (VWD) is based on the in vitro measurement of the capacity of plasma von Willebrand factor (VWF) to bind exogeneous factor VIII (VWF:FVIIIB). We report a method using only commercially available reagents that is easy to perform. This method has been validated in a cohort of 144 patients with FVIII/VWF ratios < 0.