Assays of haemostasis in the diagnosis and monitoring of haemophilia

Abstract

Optimal management of factor replacement therapies for persons with haemophilia requires accurate measurements of post-infusion factor levels to support dosing regimens that minimise the risks of bleeding events from underdosing, while preventing overdosing of expensive product. In the past 10 years there have been major additions to therapeutic options for haemophilia, including the development of extended half-life (EHL) factor replacement products and non-factor replacement therapies including bi-specific antibodies. The main aims of the current work are to evaluate and validate some of the newer methods for product measurement, supported by field studies of measurement by Australian specialist haemostasis laboratories. Emphasis has been placed on validating newer assays including the chromogenic FIX assays and emicizumab assays and exploring the suitability of current clotting and chromogenic assays for the measurement of new products. The main replacement products studied were those currently licensed for use in Australia by the National Blood Authority, and which therefore have the most relevance for specialist haemostasis testing laboratories nationwide. Recombinant factor replacement products, non-factor replacement products and gene therapies for the treatment of HA and HB continue to be developed. Each of these will need assessment in terms of best methods of laboratory measurement and their impact on other coagulation assays if or when they are funded for use in Australia.