Zero incidence of factor VIII inhibitors and successful haemostatic response in previously factor VIII-treated patients with haemophilia A switching to turoctocog alfa in a noninterventional study.

Introduction: Turoctocog alfa (NovoEight ) is a B-domain-truncated recombinant factor VIII (FVIII) approved for patients with haemophilia A.

Aim: To investigate the long-term safety and efficacy of turoctocog alfa in routine clinical practice.

Methods: Guardian 5 was a prospective, multinational, non-interventional, post-authorisation safety study.

Effectiveness and safety of hFVIII/VWF concentrate (Voncento) in patients with inherited von Willebrand disease requiring surgical procedures: the OPALE multicentre observational study.

Background: In patients with moderate to severe qualitative and quantitative von Willebrand disease (VWD), even minor surgical procedures can be associated with a risk of life-threatening bleeding. Treatment strategies vary according to the levels of von Willebrand factor (VWF) and Factor VIII (FVIII). The aim of this study was to evaluate the effectiveness and the safety of Voncento (CSL Behring, Marburg, Germany), a plasma-derived FVIII/VWF concentrate (ratio 1:2.

Gastrointestinal bleeding from angiodysplasia in von Willebrand disease: Improved diagnosis and outcome prediction using videocapsule on top of conventional endoscopy.

Background: Despite a high prevalence of angiodysplasia, no specific guidelines are available for the modalities of endoscopic exploration of gastrointestinal (GI) bleeding in von Willebrand disease (VWD). Whether VWD patients could benefit from video capsule endoscopy (VCE) looking for angiodysplasia eligible to endoscopic treatment or at high risk of bleeding is unknown.

Objectives: To assess the diagnostic efficacy for angiodysplasia and the prognostic value of VCE on top of conventional endoscopy in VWD patients with GI bleeding.

Management of von Willebrand disease with a factor VIII-poor von Willebrand factor concentrate: Results from a prospective observational post-marketing study.

Background: A triple-secured plasma-derived von Willebrand factor (pdVWF) almost devoid of factor VIII (FVIII):WILFACTIN , was approved in France in 2003, and then in other countries for the treatment of patients with von Willebrand disease (VWD).

Objective: To investigate long-term safety and efficacy of the product in real-life over the first 5 post-approval years.

Patients/methods: This prospective, observational, national post-marketing study (PMS) enrolled patients of all ages and VWD types.

Determinants of adherence and consequences of the transition from adolescence to adulthood among young people with severe haemophilia (TRANSHEMO): study protocol for a multicentric French national observational cross-sectional study.

Introduction: Severe haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life.

Point of Care Tests VerifyNow P2Y12 and INNOVANCE PFA P2Y Compared to Light Transmittance Aggregometry After Fibrinolysis.

Detection of high on-treatment platelet reactivity (HPR) by point-of-care tests has not been validated after successful fibrinolysis for ST-elevation myocardial infarction. We assessed the validity of the point-of-care VerifyNow P2Y12 (VN) and INNOVANCE PFA P2Y (PFA) tests on HPR compared to light transmittance aggregometry (LTA) in these patients. The HPR was identified in 10 (34.

A national French noninterventional study to assess the long-term safety and efficacy of reformulated nonacog alfa.

Background: Nonacog alfa, the recombinant Factor IX (F IX) used for the treatment of hemophilia B, was approved in Europe in 1998. A reformulated version was approved for European use in 2007.

Study Design And Methods: This postmarketing study, as recommended by the risk management plan, was conducted to confirm the safety of reformulated nonacog alfa in a usual care setting in France.

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.

Ability of hemostatic assessment to detect bleeding disorders and to predict abnormal surgical blood loss in children: a systematic review and meta-analysis.

Background: Systematic preoperative coagulation testing is still widely used in children scheduled for surgery, although current guidelines recommend that a bleeding history should be the first choice for hemostatic assessment. We performed a systematic review with meta-analysis to evaluate the pertinence of bleeding questionnaire and screening laboratory testing to detect bleeding disorders (BDs) in children and to predict abnormal surgical blood loss.

Methods: A search was conducted in PubMed, EMBASE, MEDLINE(R), Cochrane Central Register of Controlled Trials, Health technology Assessment, and all EBM Reviews (Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED and EBM Reviews) up to October 22, 2013.

EQOFIX: a combined economic and quality-of-life study of hemophilia B treatments in France.

Background: EQOFIX is a medicoeconomic study that analyzed the health-related quality of life (HRQoL) and costs of care of the moderate and severe forms of hemophilia B, treated on demand or by prophylaxis with either plasma-derived Factor IX (pdFIX) or recombinant FIX (rFIX).

Study Design And Methods: The primary objectives were evaluations of the impact of hemophilia B on HRQoL and of the costs associated with its management. The secondary objectives were evaluations of the clinical efficacy and costs of care of pdFIX and rFIX.

The interaction between factor H and VWF increases factor H cofactor activity and regulates VWF prothrombotic status.

Vascular endothelial cells (ECs) link hemostasis, thrombosis, and complement. ECs synthesize both the clotting initiator von Willebrand factor (VWF) and the complement regulator factor H (FH). VWF is stored in EC Weibel-Palade bodies (WPBs), but the intracellular location of FH is not well defined.

Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter.

Induction of heme oxygenase-1, a stress-inducible enzyme with anti-inflammatory activity, reduces the immunogenicity of therapeutic factor VIII in experimental hemophilia A. In humans, heme oxygenase-1 expression is modulated by polymorphisms in the promoter of the heme oxygenase-1-encoding gene (HMOX1). We investigated the relationship between polymorphisms in the HMOX1 promoter and factor VIII inhibitor development in severe hemophilia A.

Proteolytic antibodies activate factor IX in patients with acquired hemophilia.

Acquired hemophilia is a rare bleeding disorder characterized by the spontaneous occurrence of inhibitory antibodies against endogenous factor VIII (FVIII). IgG from some patients with acquired hemophilia hydrolyze FVIII. Because of the complex etiology of the disease, no clinical parameter, including the presence of FVIII-hydrolyzing IgG, has been associated with patient's survival or death.

Factor VIII-hydrolyzing IgG in acquired and congenital hemophilia.

Anti-factor VIII (FVIII) inhibitory IgG may arise as alloantibodies to therapeutic FVIII in patients with congenital hemophilia A, or as autoantibodies to endogenous FVIII in individuals with acquired hemophilia. We have described FVIII-hydrolyzing IgG both in hemophilia A patients with anti-FVIII IgG and in acquired hemophilia patients. Here, we compared the properties of proteolytic auto- and allo-antibodies.

Epidemiological survey of haemophiliacs with inhibitors in France: orthopaedic status, quality of life and cost--the 'Statut Orthopédique des Patients Hémophiles' avec Inhibiteur study.

The physical condition of severe haemophilia and the impact of advances in replacement therapy have been much studied, but little work has been done on patients who developed inhibitors. The 'Statut Orthopédique des Patients Hémophiles avec Inhibiteur' study was conducted in France in order to assess the orthopaedic status and quality of life of such patients, and the cost of their medical management. Fifty haemophiliacs aged 12-63 years with a history of high-responder inhibitors were included.

A novel Asp344Val substitution in the fibrinogen gamma chain (fibrinogen Caen) causes dysfibrinogenemia associated with thrombosis.

A 5-year-old boy was hospitalized for acute appendicitis. Routine preoperative hemostasis screening resulted in a diagnosis of dysfibrinogenemia. Fifteen days after the operation the patient was re-hospitalized for deep vein thrombosis.

Factor VIII hydrolysis mediated by anti-factor VIII autoantibodies in acquired hemophilia.

Acquired hemophilia is a rare hemorrhagic disorder caused by the spontaneous appearance of inhibitory autoantibodies directed against endogenous coagulation factor VIII (FVIII). Inhibitory Abs also arise in patients with congenital hemophilia A as alloantibodies directed to therapeutic FVIII. Both autoimmune and alloimmune inhibitors neutralize FVIII by steric hindrance.

VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors.

Von Willebrand factor (VWF) is a chaperone molecule for procoagulant factor VIII (FVIII). Its role in the reduction of the immunogenicity of therapeutic FVIII in patients with hemophilia A has been evoked but lacks clear cellular and molecular rationale. Here, we demonstrate that VWF protects FVIII from being endocytosed by human dendritic cells (DCs) and subsequently presented to FVIII-specific T cells.

Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A.

Inhibitor development is the major treatment complication in children with severe hemophilia A. It is not clear whether the risk of inhibitors is higher with recombinant factor VIII or with plasma-derived factor VIII. We used multivariate analysis to compare 2 cohorts of previously untreated patients (PUPs) with severe hemophilia A: 62 patients treated with the same brand of high-purity plasma-derived FVIII (pFVIII) containing von Willebrand factor (VWF) and 86 patients treated with full-length recombinant FVIII (rFVIII).