Hemophilia Liver Transplantation Observational Study.

Hepatitis C virus (HCV) infection is the leading cause of liver disease in hemophilia patients. In those with human immunodeficiency virus (HIV)/HCV coinfection, the rate of liver disease progression is greater than in HCV monoinfected individuals. Despite antiretroviral therapy, which slows HCV liver disease progression, some require transplantation.

Bleeding and liver transplantation outcomes in haemophilia.

Background: Hepatitis C is the major cause of end-stage liver disease and the major indication for orthotopic liver transplantation (OLTx) in individuals with haemophilia.

Aim: To assess the epidemiology and outcomes of OLTx in U.S.

Prevalence and Risk Factors Associated With Hypertension in von Willebrand Disease.

Background: von Willebrand factor (VWF) is a biomarker for endothelial damage. Increased VWF levels are observed in hypertension (HTN) and disorders of endothelial dysfunction, for example, atherosclerotic heart disease (ASHD) and diabetes. Whether low VWF protects against HTN is unknown.

Prevalence and Risk Factors Associated With Hypertension in Hemophilia: Cross-Sectional Analysis of a National Discharge Register.

Introduction: Improved life expectancy of persons with hemophilia (PWHs) has led to a greater interest in the role of age-related chronic diseases, such as hypertension, in this cohort. Several observational studies have reported an increased prevalence of hypertension in PWHs; however, this has not been assessed using a large, national database in the United States.

Aims: We hypothesized the prevalence of hypertension is increased in PWHs and compared the prevalence of hypertension and associated risk factors among patients with and without hemophilia.

Von Willebrand factor for menorrhagia: a survey and literature review.

Background: von Willebrand disease (VWD) is the most common congenital bleeding disorder. In women, menorrhagia is the most common bleeding symptom, and is disabling with iron deficiency anaemia, high health cost and poor quality of life. Current hormonal and non-hormonal therapies are limited by ineffectiveness and intolerance.

Thrombin generation and bleeding in haemophilia inhibitor patients during immune tolerance induction.

Background: Inhibitor formation complicates haemophilia treatment and requires immune tolerance induction to rid inhibitors over 5 BU. In the prospective, randomized International Immune Tolerance Study, immune tolerance induction was equally effective with high-dose (HD) (200 IU kg day ) and low-dose (LD) (50 IU kg 3× per week) factor VIII, but haemorrhages were twofold higher in the LD arm. This finding was unexpected as inhibitors neutralize FVIII activity.

Inhibitor recurrence after immune tolerance induction: a multicenter retrospective cohort study.

Background: Immune tolerance induction (ITI) in patients with congenital hemophilia A is successful in up to 70%. Although there is growing understanding of predictors of response to ITI, the probability and predictors of inhibitor recurrence after successful ITI are not well understood.

Objectives: To determine the association of clinical characteristics, particularly adherence to factor VIII (FVIII) prophylaxis after ITI, with inhibitor recurrence in patients with hemophilia A who were considered tolerant after ITI.

Does deficiency of von Willebrand factor protect against cardiovascular disease? Analysis of a national discharge register.

Introduction: von Willebrand factor (VWF) plays a critical role in platelet adhesion and aggregation after vascular injury and at sites of high shear rate. Elevated VWF levels are associated with an increased risk of ischemic cardiovascular events; however, it is unclear whether VWF deficiency is protective against atherosclerosis. We aimed to compare the prevalence of cardiovascular disease (CVD) among patients with and without von Willebrand disease (VWD).

New and Emerging Agents for the Treatment of Hemophilia: Focus on Extended Half-Life Recombinant Clotting Proteins.

Hemophilia A and B are X-linked disorders caused by deficient or defective clotting factor VIII (FVIII) or IX factor (FIX) proteins, and characterized by spontaneous or traumatic bleeding into joints and muscles. Previous use of plasma and plasma-derived clotting factors that lacked appropriate viral inactivation steps in manufacturing led to significant morbidity associated with transfusion-transmitted HIV and hepatitis C virus (HCV). The development of recombinant proteins revolutionized their treatment, and, with no new HIV or HCV infection via clotting proteins for nearly 30 years, greatly improved their lifespan, which now approaches that of the general population, and with the same risks for aging complications.

Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease.

This phase 3 trial evaluated the safety and hemostatic efficacy of a recombinant von Willebrand factor (rVWF) for treatment of bleeds in severe von Willebrand disease (VWD). rVWF was initially administered together with recombinant factor VIII (rFVIII) and subsequently alone, as long as hemostatic factor VIII activity (FVIII : C) levels were maintained. Pharmacokinetics (PK) were evaluated in a randomized cross-over design (rVWF vs rVWF:rFVIII at 50 IU VWF:ristocetin cofactor activity [RCo]/kg).

Hepatic stellate cell-conditioned myeloid cells provide a novel therapy for prevention of factor VIII antibody formation in mice.

A major complication of factor VIII (F.VIII) infusion therapies for the treatment of hemophilia A is the formation of antibodies (inhibitors) against F.VIII, a T-cell-dependent, B-cell-mediated process.

Venous thromboembolism in pregnant women with sickle cell disease: a retrospective database analysis.

Introduction: The risk of venous thromboembolism (VTE) is higher during pregnancy, with an incidence between 0.05 and 0.2%, and among persons with sickle cell disease (SCD), yet the rates and risk factors, such as pneumonia, vasooclusive crisis (VOC), and acute chest syndrome (ACS), associated with pregnancy-related VTE are not firmly established in SCD.

Pharmacokinetic analysis of anti-hemophilic factor in the obese patient.

Standard dosing for individuals with hemophilia A is based on body weight such that 50 IU kg(-1) is defined as a 100% dose, or one attaining 1.00 IU mL(-1) factor VIII (FVIII) clotting activity. No guidelines exist, however, for individuals with hemophilia who are obese, body mass index (BMI) ≥ 30, who may actually be 'over'-treated based on higher in vivo recovery based on higher weight.

Rationale for a randomized controlled trial comparing two prophylaxis regimens in adults with severe hemophilia A: the Hemophilia Adult Prophylaxis Trial.

A major goal of comprehensive hemophilia care is to prevent occurrence of bleeds by prophylaxis or regular preventive factor, one or more times weekly. Although prophylaxis is effective in reducing bleeding and joint damage in children, whether it is necessary to continue into adulthood is not known. The purpose of this article is to describe a Phase III randomized controlled trial to evaluate prophylaxis comparing two dose regimens in adults with severe hemophilia A.

Viral pathogens.

Despite continuous improvement in safety and purity of blood products for individuals with haemophilia, transmissible agents continue to affect individuals with haemophilia. This chapter addresses three viral pathogens with significant clinical impact: HIV, hepatitis C and parvovirus B19. Hepatitis C is the leading cause of chronic hepatitis and the major co-morbid complication of haemophilia treatment.

Clinical manifestations and management of labor and delivery in women with factor IX deficiency.

Haemophilia is uncommon in females and little is known about the clinical manifestations and postpartum management of women with this disorder. Clinical characteristics of postpartum bleeding were evaluated in women with factor IX deficiency (FIX:C < 0.20 U mL(-1)), including two with haemophilia B and three carriers of haemophilia B, undergoing labour and delivery.

Bleeding manifestations in males with von Willebrand disease.

von Willebrand disease (vWD) is the most common congenital bleeding disorder in the USA, affecting 1-3% of the population. Previously characterizing the bleeding symptoms in females with type 1 vWD, we evaluated 42 males with type 1 vWD, mean age 16 years (1-64), of whom 24 (57%) presented with bleeding symptoms. The most common initial symptom was postoperative bleeding (26%).

Safety of the new generation recombinant factor concentrates.

Haemophilia A and B are X-linked disorders resulting from deficiency of Factor VIII and IX, respectively. Clinical sequellae of Factor VIII or IX deficiency include spontaneous and traumatic haemorrhages into joints, soft tissues, and muscles. The cornerstone of therapy has been replacement of the deficient factor, historically with pooled-plasma derivatives.

Use of recombinant factor IX in subjects with haemophilia B undergoing surgery.

Recombinant human FIX (rFIX) was evaluated in 28 subjects, including 26 with mild, moderate, or severe haemophilia B and two haemophilia B carriers undergoing 36 surgical procedures. Preoperative rFIX dose was highly correlated with postinfusion FIX activity, r=0.61, P=0.