Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States.

von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria.

A longer acting rFVIII, safe and effective.

In this issue of Blood, Mahlangu et al describe a well-designed and executed phase 3 multicenter study of a recombinant factor VIII (rFVIII) product fused with the Fc fragment of immunoglobulin G1 (IgG1) in 165 patients with severe hemophilia A.

Phenotypes of allo- and autoimmune antibody responses to FVIII characterized by surface plasmon resonance.

Evidence of antibody isotype/subtype switching may provide prognostic value regarding the state of immune responses to therapeutic proteins, e.g. anti-factor VIII (FVIII) antibodies that develop in many hemophilia A patients, clinically termed "inhibitors".

No increase in bleeding identified in type 1 VWD subjects with D1472H sequence variation.

The diagnosis of von Willebrand disease (VWD) is complicated by issues with current laboratory testing, particularly the ristocetin cofactor activity assay (VWF:RCo). We have recently reported a sequence variation in the von Willebrand factor (VWF) A1 domain, p.D1472H (D1472H), associated with a decrease in the VWF:RCo/VWF antigen (VWF:Ag) ratio but not associated with bleeding in healthy control subjects.

Emergency department visits in children with hemophilia.

Background: The pediatric emergency department (ED) management of bleeding and other complications of hemophilia constitutes an increasingly important component of hemophilia therapy. This retrospective study examined the overall ED use by children with hemophilia in a single center, with a particular aim to investigate visits related to injury or bleeding, and those related to blood stream infection in patients with a central venous catheter (CVC).

Methods: Electronic medical records of patients with hemophilia presenting to Children's Hospital of Michigan ED were reviewed.

VWF mutations and new sequence variations identified in healthy controls are more frequent in the African-American population.

Diagnosis and classification of VWD is aided by molecular analysis of the VWF gene. Because VWF polymorphisms have not been fully characterized, we performed VWF laboratory testing and gene sequencing of 184 healthy controls with a negative bleeding history. The controls included 66 (35.

A community-based partnership to promote information infrastructure for bleeding disorders.

Specialists in rare disorders often face challenges in collecting surveillance and research data. As movement toward more fully realizing the potential of electronic health information gains momentum, practitioners who treat individuals with rare disorders are in need of public-private support to tap into the advantages offered by the developing electronic information technologies and the interoperability standards promulgated by the USDHHS. The not-for-profit American Thrombosis and Hemostasis Network (ATHN) was created in 2006 to provide stewardship of a secure, national, web-based database to support federally funded hemophilia treatment centers (HTCs) across the country.

Fibrinolytic parameters in children with noncatheter thrombosis: a pilot study.

Although the incidence of pediatric thrombosis has increased over the last decade, noncatheter-related deep venous thrombosis (nCDVT) is rare in children. Congenital and acquired hypercoagulable states may play an important role in the pathogenesis of nCDVT. In this study, we evaluated fibrinolytic parameters by measuring individual concentrations of fibrinolytic proteins and by tissue factor initiated whole blood thromboelastography (TEG), in which a fibrin clot was lyzed by exogenously added tissue plasminogen activator (tPA).

Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor.

The diagnosis of von Willebrand disease relies on abnormalities in specific tests of von Willebrand factor (VWF), including VWF antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:RCo). When examining healthy controls enrolled in the T. S.

Evolution of recombinant factor VIII safety: KOGENATE and Kogenate FS/Bayer.

The use of factor VIII (FVIII) concentrates in the treatment of hemophilia A has raised important safety issues, historically of pathogen transmission and increasingly of inhibitor development to FVIII treatment. While manufacturing processes of current recombinant FVIII products have been shaped entirely around preventing pathogen transmission, the same modifications that afford a greater margin of safety could affect immunogenicity of the product, consequences of which could only be seen through long-term clinical experience. This review summarizes pathogen safety and inhibitor reports from clinical trials, post-marketing surveillance studies, and study reports on KOGENATE and its successor, Kogenate FS/Bayer.

Decreased clearance of von Willebrand factor in a patient with type 2B von Willebrand disease following development of immune thrombocytopenia.

We report a case of concurrent type 2B von Willebrand disease (VWD) and immune thrombocytopenia (ITP). The patient had characteristic loss of von Willebrand factor (VWF) high molecular weight multimers (HMWM) but a normal platelet count in the initial 8 years after diagnosis of type 2B VWD. When he developed severe thrombocytopenia, however, both his VWD indices and VWF HMWM normalized.

Thromboelastography in children with coagulation factor deficiencies.

Hemophilia is traditionally classified according to the levels of the deficient coagulation factor as Severe (<1%), Moderate (1-5%) or Mild (>5%). However, it is well known that the factor activity does not necessarily correspond to the clinical bleeding manifestations. As prophylactic therapy is the best method of prevention of serious complications such as hemophilic arthropathy, a test that may predict the bleeding pattern would be extremely beneficial.

How do you treat bleeding disorders with desmopressin?

Desmopressin is an analog of vasopressin that exerts a substantial haemostatic effect by inducing the release of von Willebrand factor from its storage sites in endothelial cells. It has proved useful in treating or preventing bleeding episodes in patients with von Willebrand disease, haemophilia A and platelet function defects. Its efficacy in achieving a satisfactory level of haemostasis has reduced the use of blood products to treat bleeding episodes.

Pediatric reference values for molecular markers in hemostasis.

Background: The hemostatic system is a developing and changing process relative to age.

Objectives: To distinguish the differences in hemostatic parameters between children and adults, and to establish the normal range of these parameters in children of different age groups.

Design/methods: Blood was obtained from healthy children aged 1 to 18 years (n=70) and adults (n=26).

Milestones in hemophilia and concepts in future clinical trial design.

Hemophilia has long been documented as a bleeding disorder that afflicts males from early childhood. While some early societies set guidelines or laws to protect affected children, true advances in the understanding of the underlying deficiency and in the treatment of hemophilia have been relatively recent and continue today. This paper presents some of the key milestones that mark the path to current knowledge on hemophilia.

Full-length sucrose-formulated recombinant factor VIII for treatment of previously untreated or minimally treated young children with severe haemophilia A: results of an international clinical investigation.

The safety and efficacy of a full-length sucrose-formulated recombinant factor VIII product (rFVIII-FS; Kogenate FS; Kogenate Bayer) was evaluated in previously untreated (PUPs) and minimally treated (MTP) patients with severe haemophilia A (FVIII <2%). Patients (37 PUPs; 24 MTPs) aged 0.1-25.

The safety and efficacy of recombinant human blood coagulation factor IX in previously untreated patients with severe or moderately severe hemophilia B.

This international clinical trial evaluated the safety and efficacy of recombinant factor IX (rFIX) in previously untreated patients (PUPs) with severe or moderately severe hemophilia B (FIX activity, < or = 3 IU/dL). Sixty-three PUPs aged younger than 1 month to 14 years received rFIX (median treatment duration, 37 months; range, 4-64 months). Mean rFIX recovery (0.

Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion.

In a phase 1 dose escalation study, 13 subjects with hemophilia A received by peripheral intravenous infusion a retroviral vector carrying a B-domain-deleted human factor VIII (hFVIII) gene. Infusions were well tolerated. Tests for replication competent retrovirus have been negative.

First and second generation recombinant factor VIII concentrates in previously untreated patients: recovery, safety, efficacy, and inhibitor development.

The first of the prospective multicenter studies in previously untreated patients (PUPs) with a recombinant factor VIII (FVIII) concentrate began in January 1989. Over the past 11 years, PUP studies have amassed a great deal of information concerning safety, efficacy, and inhibitor development of the two "first-generation" recombinant (r) FVIII concentrates (Kogenate and Recombinate) and of two "second-generation" products (ReFacto and Kogenate FS, which is formulated with sucrose rather than with albumin). Each of these products has proved to be safe, effective, and well-tolerated.

Congenital Hemorrhagic Disorders: New Insights into the Pathophysiology and Treatment of Hemophilia.

The diagnostic and treatment strategies related to hemophilia are rapidly evolving. This article focuses on some of the issues of importance. Diagnostic advances in molecular genetics are reviewed by Dr.