Early detection of the appearance of inhibitors is a key element in enabling their timely eradication. The Bethesda test is a simple and reliable way to detect the presence of inhibitors; however, in order for it to prove a truly effective weapon in the battle against inhibitors, it must be carried out at specific time-points during replacement therapy, when the risk of their appearance is particularly high.

In PUPs (Previously Untreated Patients), for example, the first 75 days of treatment are those in which there is the highest risk of inhibitors occurring, and consequently the test should be performed with the following frequency:

  • every 3 days, during the first 20 days of therapy;
  • every 10 days between 21 and 50 days of therapy;
  • beyond the first 50 days, the test should be repeated at least twice a year, up to 150 days of therapy.

Once the first 150 days have passed, the risk of developing inhibitors becomes extremely low, so it is sufficient to run the test just once a year as preventive screening. However, the test should also be carried out before undergoing any surgical procedure, if the product used for replacement therapy is changed, and whenever a decrease in the effectiveness of the therapy is observed.


  • Giangrande P. L. F. et al. European principles of inhibitor management in patients with haemophilia. Orphanet Journal of Rare Diseases, 2018. 13(1):66
  • Marijke van den Berg H. et al. Timing of inhibitor development in more than 1000 previously untreated patients with severe hemophilia A. Blood, 2019. 134:317-320
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Learn more about the meaning of the words you read on this page and learn about the entire glossary on hemophilia.

Acronym for “Previously Untreated Patients”, i.e. patients who have never been treated with replacement factor VIII.

Therapy for the treatment of haemophilia A, consisting in the intravenous administration of the lacking factor VIII, thereby restoring a correct blood-clotting process and preventing bleeds.

Replacement therapy can be administered in accordance with two treatment regimens: as on-demand or prophylactic therapy.