Pitfalls in the diagnosis of hemophilia severity: What to do?

Abstract

Measurements of factor VIII coagulation activity (FVIII:C) may vary and result in misclassification of hemophilia A with delay in initiation of prophylactic treatment. We describe two young brothers who were diagnosed as moderate hemophilia patients and therefore not prophylactically treated with factor VIII concentrate despite frequent bleeding events. These findings emphasize the importance of (i) multiple measurements of FVIII:C by certified laboratories, (ii) adjustment of treatment when test results do not correspond to clinical symptoms, (iii) relevance of additional DNA mutation analysis in patients with hemophilia A, and (iv) treatment in centers with expertise.

Analytical variation in factor VIII one‐stage and chromogenic assays: Experiences from the ECAT external quality assessment programme

“…Statistical significance is indicated as *P < 0.05, **P < 0.01, *** P < 0.001 which may also have influenced the FVIII activity levels found in this study 12. High between-laboratory CVs may influence diagnoses of haemophilia A patients between hospitals as reported previously 4. Already, small absolute differences in FVIII activity may result in mis-classification and suboptimal treatment.…”

“…High between‐laboratory CVs may influence diagnoses of haemophilia A patients between hospitals as reported previously . Already, small absolute differences in FVIII activity may result in misclassification and suboptimal treatment.…”

“…We recently showed that despite excellent performance in the ECAT external quality assessment programme, between-laboratory variation may result in different FVIII levels, and consequently, in misclassification of haemophilia severity. 4 Limited between-laboratory variation in FVIII activity levels is also of importance for the monitoring of treatment in patients with haemophilia A, as specific target FVIII activity levels should be maintained around surgery and bleeding episodes. 1,2,5 Two assays are widely used to measure FVIII activity: the onestage assay (OSA) and the two-stage chromogenic substrate assay (CSA).…”

“…Measuring FVIII activity levels accurately and reproducibly in different laboratories is therefore essential. We recently showed that despite excellent performance in the ECAT external quality assessment programme, between‐laboratory variation may result in different FVIII levels, and consequently, in misclassification of haemophilia severity . Limited between‐laboratory variation in FVIII activity levels is also of importance for the monitoring of treatment in patients with haemophilia A, as specific target FVIII activity levels should be maintained around surgery and bleeding episodes …”