Practical Advances in the Diagnosis of Haemophilia and von Willebrand Disease Including Monitoring of Non-Factor Replacement Therapies.

Traditional haemophilia therapies act to replace the relevant missing clotting factor, are not interchangeable between haemophilia A and B and cannot be used in patients with high titre inhibitors. Novel non-replacement factor therapies (NFT) target other endogenous coagulation proteins or anticoagulants such as antithrombin (AT) and tissue factor pathway inhibitor (TFPI) to rebalance haemostasis. As such, pharmaceutical clinical trials of these molecules have enrolled patients with haemophilia A or B, with and without inhibitors. The requirement for monitoring the efficacy of NFTs is greatly reduced compared to replacement therapy and global assays such as thrombin generation assay (TGA) have been used extensively in clinical trials to indicate improvement to haemostasis. Comprehensive haemophilia care, including access to and laboratory monitoring of replacement and NFTs, is well established in high income countries, but there are profound global inequities in the diagnosis and treatment of haemophilia which still need to be remedied. The authors examine the challenges of haemophilia and von Willebrand diagnosis and monitoring of NFTs using conventional and global assays of haemostasis.