Vigorous activity briefly raised bleeding risk in youth with hemophilia

William T. Gerson, MD

Broderick and colleagues’ study of the risk of bleeding resulting from increased levels of vigorous activity among children and adolescents with moderate to severe hemophilia (A and B) has several implications for general pediatricians. Their well-designed rigorous trial reveals an increased rate of bleeding requiring acute factor replacement immediately following at-risk activity, with an odds ratio of 2.7 for category 2 activities (eg, basketball) and 3.7 for category 3 activities (eg, wrestling) as compared with inactivity and category 1 activities ( eg, swimming). Most participants (89%) in this Australian trial were receiving standard prophylactic factor replacement therapy. In absolute terms, because high level activity is limited to several episodes per week, the contribution of vigorous activity to the overall number of bleeds is small. On an annual basis, it is estimated to account for one of the five average experienced bleeds per year requiring acute factor infusion in this population. Importantly, the authors also found that for every 1% increase in factor clotting level, bleeding incidence was lower by 2%.

Most of us in office practice do not see very many patients with hemophilia, if at all. However, the importance of an appropriately powered and insightful study to investigate a clinical assumption of unknown magnitude, in this case the risk of bleeding in hemophiliacs from sports participation, should not go unnoticed. Putting limits on an area of clear importance to the well-being of our patients without adequate data is, and always has been, troubling. Socially, emotionally and physically, exercise is an important aspect of a child’s life. For one who already has a chronic disease that in many small and not so small ways separates one from one’s peers, a “diffability” at the very least, even further ostracization is indeed harmful.  If we haven’t measured the true risk, we make poor judgments in their care.

How are we doing with guidance for exercise limitation for those with multiple concussions, loss of paired organs, enlarged hearts (or aortic roots) or, for that matter, driving and ADHD? I applaud the authors on their attempt to answer such an important question for our patients and their families. In so doing, their carefully acquired data also bring up the interesting potential of more frequent or targeted factor infusion programs to both decrease the incidence of bleeding episodes but to more safely allow vigorous participation in physical activities in the hemophilia population. There is no end to interesting questions in clinical pediatrics.

Katherine A. High, MD

This case-crossover study in 104 Australian children and adolescents with severe or moderately severe hemophilia — 85% of whom were on prophylaxis — found an increase in risk of bleeds in association with physical activity, with those activities characterized by a greater frequency and severity of collisions associated with greater risk. However, overall the increase in risk in this group of children was very modest. For a child with a moderate level of physical activity, it amounted to only one additional bleed per year. Though there were many limitations to the study, the data provide a useful baseline, particularly as new products — including long-acting factor and gene therapy approaches — enter the treatment landscape.

Nigel Key, MB, ChB, FRCP

This study is an important landmark in the evolving success story of hemophilia over the past 3 decades. The availability of prophylactic therapy — given on a regular basis two to three times per week — in these boys has led to a remarkable improvement in musculo-skeletal health. Indeed, some children with severe or moderate hemophilia do not even know what it is to experience a joint bleed. This success story has been accompanied by an increasing participation of hemophilic boys in sporting activities.

This study tells us that, given some tolerance for rare bleeds that may occur, these boys can safely participate in the majority of sports, even those that involve moderate contact. This study also reminds us that, in the upcoming era of long-acting bioengineered Factor VIII and Factor IX products, an “adequate” plasma level is a somewhat arbitrary concept that will need to be individualized, depending on the patient’s pharmacokinetic profile and desired activity level.