The availability of a murine model for haemophilia A has allowed for pursuing novel
approaches for treatment and prevention Ruxolitinib in vitro of inhibitor development in haemophilia A. An interesting approach involves the use of transduced B cells expressing Ig-fusion proteins comprising A2 and C2 domain for prevention of inhibitor development in murine haemophilia A . Interestingly, a decline in pre-existing levels of FVIII inhibitors was also observed following transfer of B cells expressing these Ig-fusion proteins in haemophilia A mice with pre-existing inhibitors. B cell responses following infusion of FVIII in haemophilia A mice have been extensively characterized [10,53,55,56]. An important and challenging finding from these studies was the reported effect of high dosages of FVIII in prevention of the re-stimulation of memory B cells . This finding has stimulated efforts to analyse circulating FVIII-specific memory B cells in patients with haemophilia A [33,34]. From these studies it followed that the frequency of FVIII-specific memory B cells is similar to observed in the context of vaccination. Future studies are needed to study the dynamics of FVIII-specific memory B cells in haemophilia
A patients with inhibitors. Moreover, information on the presence and persistence of long-living plasma cells secreting anti-FVIII antibodies in bone marrow and spleen is needed to be able to design novel therapies for treatment Palbociclib datasheet of haemophilia A patients with inhibitors. The authors stated that they had no interests which might be perceived as posing a conflict or bias. “
“Summary. In this paper, the recent developments in the diagnosis and laboratory issues of von Willebrand’s MCE disease (VWD) are presented. Dr. Castaman reviews the functional tests available for the diagnosis of VWD and their pathophysiological significance, focusing on which tests are best used in the diagnosis and classification of VWD. Dr Montgomery reviews an emerging issue that is accelerated clearance of von Willebrand
factor (VWF) occurring in some variants of VWD. This phenotype can be suspected by the presence of an increased ratio between the VWF propeptide and the VWF antigen. These patients have typically a robust, but short-lived increase of FVIII and VWF after desmopressin. Dr Meschengieser reviews the determinants of bleeding after surgery in patients with VWD, emphasizing the role of bleeding history in predicting this risk. von Willebrand factor (VWF) is a multimeric glycoprotein synthesized by endothelial cells and megakaryocytes and plays two major functions in haemostasis . First, it is essential for platelet adhesion to the subendothelium and platelet-to-platelet interactions as well as platelet aggregation in vessels in which rapid blood flow results in elevated shear stress.