Current Expert Consensus on Prophylaxis of Individuals with Mild and Moderate Hemophilia A: These Patients Also Deserve Better Care

An Underestimated Group of Hemophiliacs...

Hemophilia A is a congenital bleeding disorder caused by a deficiency of clotting factor VIII (FVIII). For individuals with the severe form of hemophilia, prophylaxis, i.e., the preventive administration of FVIII concentrate, is now the standard of care. Introducing prophylaxis into the care of hemophiliacs with significant bleeding tendencies has reduced the number of bleeding episodes and consequently improved the reported quality of life. On the other hand, prophylaxis remains a less likely part of the treatment strategy for moderate and especially mild hemophilia A. Nevertheless, it is evident that a significant portion of the so-called non-severe hemophiliac population shows signs of joint damage in adulthood.

The fact is that even in routine clinical practice, the possibility of joint damage in mild and moderate hemophiliacs is often overlooked. The DYNAMO study showed that the median age of the first joint bleed was 7 years (interquartile range [IQR] 4−15) in 70 hemophiliacs with moderate hemophilia and 13 years (IQR 7−20) in 234 mild hemophiliacs. This is similar to some previously reported observations.

...and Who Can Benefit Most from Prophylaxis?

Based on these studies and their own clinical practice, Italian experts in the cited consensus state that roughly 30% of moderate hemophiliacs and a small percentage of mild hemophiliacs would be suitable candidates for prophylactic treatment. Parameters that might help identify those hemophiliacs who would also benefit from prophylactic treatment similarly to severe hemophiliacs could include:

• Assessment of the first occurrence of spontaneous bleeding − considering age.
• Occurrence of spontaneous bleeding in critical areas (e.g., muscle, intracranial, large subcutaneous bleeding).
• Bleeding phenotype and number of bleeds per year – for patients not treated with prophylaxis, for example, more than 10 bleeds per year or even 5 bleeds per year (including traumatic ones) should lead doctors to consider prophylaxis. In the case of more than 2 spontaneous bleeds per year, the initiation of prophylaxis should again be considered.
• Early joint degenerative signs (i.e., presence of synovitis) according to ultrasound examination.
• Presence of risk factors (obesity, reduced physical activity, physical employment, etc.)
• Presence of comorbidities (e.g., oncological disease, cardiovascular disease, HIV/HCV positivity).
• Patient expectations (depending on lifestyle and daily activities).

Generally, the Italian experts agreed that initiating prophylaxis only after proving degenerative joint changes is too late. Hence, this criterion is considered inappropriate.

Conclusion

The criteria mentioned are primarily applicable to patients with moderate hemophilia but certainly also to a smaller portion of those with a mild form of hemophilia. The issue is even more relevant as modern treatment offers a slightly less burdensome need for injections within long-term prophylaxis. Therefore, it would be appropriate to verify the feasibility and benefits of longer-term prophylactic treatment in this population of hemophiliacs in controlled studies.

(eza)

Source: Castaman G., Peyvandi F., De Cristofaro R. et al. Mild and moderate hemophilia A: neglected conditions, still with unmet needs. J Clin Med 2023 Feb 8; 12 (4): 1368, doi: 10.3390/jcm12041368.