Monitoring inhibitor patients with the right assays.
The inhibitor titer is the most important clinical measurement in inhibitor patients, and the Nijmegen method is preferable to the original and well-established Bethesda assay for this purpose; however, both methods have high inter-laboratory variability. Monitoring inhibitor patients after treatment with bypassing agents is difficult. Treatment with recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) can be monitored with assays for FVII clotting activity or with a specific assay for FVIIa; while the latter is more reproducible, its relevance to the clinical response of individual patients remains unclear. Recent years have also witnessed a revival of global assays, which contribute useful additional information and which may be more relevant to the hemostatic state of individual inhibitor patients. One such assay currently undergoing a renaissance is the thrombin generation test (TGT). The TGT has many methodological variations--several of which have been studied in our laboratory--and shows the most promise for use in treatment monitoring. This article reviews the assays most appropriate for monitoring inhibitor patients and discusses some of the most recent developments in the use of global assays in this indication.
Barrowcliffe
Trevor W
TW
National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, UK. twbarrowcliffe@yahoo.co.uk
D019774:Blood Coagulation Factor Inhibitors / Q000097:blood* / Q000502:physiology; D001779:Blood Coagulation Factors / Q000276:immunology / Q000627:therapeutic use; D001780:Blood Coagulation Tests / Q000379:methods*; D005169:Factor VIII / Q000276:immunology; D015942:Factor VIIa / Q000627:therapeutic use; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D011994:Recombinant Proteins / Q000627:therapeutic use
D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII; C103587:recombinant FVIIa; D015942:Factor VIIa