Recommendations for the assay of modified FVIII and FIX products have been developed by ISTH/SSC and recently published [34]. Looking back over the last 50 years, considerable progress has been made in the standardization of laboratory tests and assays. Compared with the 10-fold range of potencies found for the FVIII concentrate in
the first international collaborative study, in recent studies all labs are within 20% of the mean. It is also gratifying that all manufacturers, both of concentrates and of diagnostic plasma standards use International Standards to calibrate their CX-4945 order products. The new products present challenges to standardization, but with the spirit of cooperation, which has developed over the years between manufacturers, regulatory agencies and clinical labs these can be overcome. The author stated that he had no interests which might be perceived
as posing a conflict or bias. “
“Summary. Studies of determinants of the development of inhibitory antibodies in patients with haemophilia indicate that this is a complex process involving several factors. The foundation is characterized by the T- and B-cell repertoire and the antigen presenting cells and to elicit an immune response to the deficient factor, a pre-disposing foundation is needed. Hence, in the absence of a certain set of circumstances, there will be no risk for development of inhibitors. Conversely, in patients fundamentally at risk, genetic and non-genetic factors might add to the risk. These factors may be additive or interactive, and ultimately promote or counteract the immune reaction by modifying immune regulators and the cytokine profile MK-8669 molecular weight in an individual. In some subjects, only minor MCE公司 inflammatory signals might be needed, whereas in others a more pronounced pro-inflammatory
state will be required. Regarding genetic markers other than the type of mutation and the HLA class II molecules, polymorphisms in various immune regulatory genes have been associated with inhibitor risk. These associations have not, however, been consistent across all patient groups. The reason for this is not clear, but could be related to study design or statistical power, family relationships among those studied, the complexity of interacting molecules and ethnic genomic variation. The Hemophilia Inhibitor Genetics Study (HIGS) has identified additional candidates within the intracellular pathways, all of which require additional evaluation to be fully appreciated. In the case of non-genetic factors, the overall view is that immune system challenges might add to the risk. HIGS data suggest that it will be possible to calculate a genetic score to identify patients at high risk for inhibitor development before the start of treatment. By doing so, it may hopefully be possible in the future to prevent the formation of inhibitors in these patients by offering therapeutic options other than the native factor VIII or IX molecule in an inflammatory setting.