The quality of hemophilia clinical practice guidelines (CPGs) is not ideal, with varying recommendations on prophylaxis and a lack of justification for these endorsements, according to findings from a comprehensive review published in the journal Health Science Reports.

In patients with hemophilia, disease management is based on deficient clotting factor concentrates or bypass agents in the presence of inhibitors. In affected individuals, factor concentrate is indicated as a prophylactic initiative for the prevention of long-term complications, including arthropathy.

Although CPGs release recommendations about which patients should receive primary prophylaxis with clotting factor concentrates and the appropriate dose, these recommendations are heterogeneous across countries. The researchers of the current study sought to perform a scoping review of CPGs to address hemophilia management, evaluate their methodologic quality, and compare their recommendations for prophylaxis with clotting factor concentrate.

Continue Reading

Eleven hemophilia CPGs were selected that issued prophylaxis recommendations. They were published or updated between 2017 and 2021. Among the 11 CPGs included in the study, the following findings were reported:

  • 3 of the 11 CPGs involved patients or their representatives in the process of developing a particular CPG.
  • 6 of the 11 CPGs used the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to issue their recommendations.
  • 2 of the 11 CPGs included Summary of Findings tables.
  • 5 of the 11 CPGs were developed in upper-income or middle-income countries.

Read more about experimental therapies for patients with hemophilia

The Appraisal of Guidelines for Research & Evaluation Instrument-II (AGREE II) instrument was used to evaluate the methodologic quality of all CPGs included and to compare their recommendations for prophylaxis. In fact, the overall assessment score on AGREE II ranged from 14% to 83%, with 3 of the 11 CPGs having an overall assessment score of 60% or more.

The recommendations on prophylaxis initiation were heterogeneous, as follows:

  • 3 of the 11 CPGs recommended initiating prophylaxis in patients with moderate or severe hemophilia.
  • 4 of the 11 CPGs recommended initiating prophylaxis in patients with severe hemophilia.
  • 3 of the 11 CPGs did not mention whether disease severity is a criterion for initiation of prophylaxis.
  • 1 of the 11 CPGs did not issue any recommendation regarding prophylaxis initiation.

Taking into consideration the World Federation of Hemophilia International guideline classification of dosing in prophylaxis, the following recommendations were issued:

  • 4 of the 11 CPGs considered initiating prophylaxis at a low dose.
  • 6 of the 11 CPGs considered initiating prophylaxis at an intermediate or a high dose.
  • 1 of the 11 CPGs did not issue a recommendation regarding prophylactic dosing.

Despite these recommendations on initiation of prophylaxis and dosing in prophylaxis, only 2 of the 11 CPGs offered justification for their recommendations, with no economic assessments performed to support these recommendations.

“The quality of hemophilia CPGs is not optimal, with inconsistent recommendations for prophylaxis and a lack of justification for these recommendations,” the researchers emphasized. “To ensure evidence-based and trustworthy recommendations, there is a need for transparency and improvement in the decision-making process of hemophilia CPGs,” they concluded.


Delgado-Flores CJ, García-Gomero D, Pinedo-Castillo L, Taype-Rondan A. Methodological quality and recommendations of hemophilia clinical practice guidelines: a scoping review. Health Sci Rep. Published online July 13, 2023. doi:10.1002/hsr2.1326