Clinical phenotype of severe and moderate haemophilia: Who should receive prophylaxis and what is the target trough level?

Introduction: One of the most often stated tenets of haemophilia care is that prophylaxis converts a person from a severe to a moderate phenotype. In this review, we argue that this is not an accurate assumption and that people on prophylaxis predominantly have factor VIII/IX levels in the mild range.

Moderate Haemophilia And Prophylaxis: People with moderate haemophilia, who are treating with on-demand regimens, experience joint bleeds and often develop significant arthropathy.

The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles.

Tissue factor (TF) is critical for the activation of blood coagulation. TF function is regulated by the amount of externalised phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the surface of the cell in which it is expressed. We investigated the role PS and PE in fibroblast TF function.

Phenotype description and response to thrombopoietin receptor agonist in -related disorder.

-related disorder has a bilineage hematological phenotype of macrothrombocytopenia and neutropenia associated with hearing loss. Eltrombopag increased proplatelet formation from cultured -related disorder megakaryocytes and improved platelet counts in vivo.

Mutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia.

Platelets are anuclear cells that are essential for blood clotting. They are produced by large polyploid precursor cells called megakaryocytes. Previous genome-wide association studies in nearly 70,000 individuals indicated that single nucleotide variants (SNVs) in the gene encoding the actin cytoskeletal regulator tropomyosin 4 (TPM4) exert an effect on the count and volume of platelets.

Role of enhanced half-life factor VIII and IX in the treatment of haemophilia.

Treatment of congenital haemophilia with factor VIII and IX concentrates often requires frequent infusions. This has obvious implications in establishing effective administration strategies and, in turn, adherence. To overcome these issues, three main technologies--polyethylene-glycol, Fc-neonatal IgG1 and albumin fusion products--have emerged into various stages of clinical development.

Isolated folate deficiency causing profound pancytopenia in pregnancy.

New-onset pancytopenia in pregnancy is challenging in the clinical setting particularly as the management and outcome of pregnancy are entirely dependent on the underlying aetiology. In the absence of increased peripheral destruction, for example, hypersplenism, bone marrow (BM) failure should be considered as the cause of pancytopenia. Profound folate or B12 deficiency may result in BM failure and are relatively easy to diagnose and manage.

Chiari network: a protective filter against pulmonary embolism in a case of polycythaemia.

The Chiari network, a net-like structure within the right atrium, has been described as an embryonic remnant of no clinical significance. Its role in facilitating paradoxical arterial embolic events and as a potential site for thrombus formation however, has been reported in the literature. This case illustrates the protective filter-effect of the Chiari network in a 79-year-old Caucasian man with an unknown diagnosis of polycythaemia rubra vera who presented with clinical signs and symptoms of deep vein thrombosis.