October 11, 2012
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Vigorous activity briefly raised bleeding risk in youth with hemophilia

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In children and adolescents with hemophilia, energetic physical activity was briefly associated with a moderate relative increase in risk for bleeding, according to study results in the Oct. 10 issue of The Journal of the American Medical Association.

However, because the increased RR is temporary, the absolute increase in risk for bleeding associated with physical activity is expected to be minute.

In previous studies, prophylactic injections of recombinant Factor VIII have been shown to reduce the risk for bleeds in children with hemophilia, but the clinical effects of lower doses have not been strictly tested.

“The reduction in risk of bleeds conferred by prophylaxis may be such that the benefits of physical activity outweigh the risk of bleeds,” Carolyn R. Broderick, MBBS, of the University of Sydney, Australia, and colleagues wrote. “However, the degree to which risk of bleeds is elevated by physical activity has not been determined. Information about risks associated with physical activity is needed to inform decisions about participation in physical activity and to optimize prophylactic schedules.”

To calculate the temporary increase in risk of bleeding associated with vigorous physical activity in children with hemophilia, Broderick and colleagues conducted a study of 104 children and adolescent boys aged 4 to 18 years, with moderate or severe hemophilia A or B who were monitored for bleeds for up to 1 year.

After each bleed, the child or parent was interviewed to establish exposures to physical activity before the bleed. Physical activity was classified according to expected frequency and severity of collisions.

The risk for bleeds connected with physical activity was calculated by contrasting exposure to physical activity in the 8 hours preceding the bleed with exposures in two 8-hour control (non-bleed) windows, controlling for levels of clotting factor in the blood.

During the study, there were 436 reported bleeds, 336 of which were study bleeds, such as bleeding episodes without another bleeding episode in the preceding 2 weeks. Eighty-eight participants (84%) reported at least one bleed, with the most frequent sites of bleeding located on the knee (15%), ankle (14%) and elbow (10%).

According to study results, compared with inactivity and activities with a low risk for collision, activities with an increased risk for collision were associated with a brief increase in the risk for bleeding (30.6% of bleed windows vs. 24.8% of first control windows; OR, 2.7; 95% CI, 1.7-4.8). In addition, close contact and collision-prone activities were associated with a greater transient increase in risk (7% of bleed windows vs. 3.4% of first control windows; OR, 3.7; 95% CI, 2.3-7.3).

To illustrate absolute risk increase, for a child who bleeds five times annually and is exposed on average to category 2 activities (eg, basketball) twice weekly and to category 3 activities (eg, wrestling) once weekly, exposure to these activities was associated with only one of the five annual bleeds. For every 1% increase in clotting factor level, bleeding incidence was lower by 2% (P=.004).

“The risk of bleeding is mitigated by prophylaxis to the extent that clotting factor levels of around 50% reduce risk of bleeds to below the risk experienced during periods of inactivity with no exogenous clotting factor,” Broderick and colleagues wrote. “With typical prophylaxis regimens, peak factor concentrations of 70% to 100% are achieved which, given a factor VIII half-life of 10.7 hours, is sufficient to maintain levels greater than 50% for between approximately 6 and 12 hours.

“In contrast, factor supplementation reduces risk for long periods yielding sustained reductions in relative risk,” the researchers wrote. “Consequently prophylactic clotting factor is likely to have a larger absolute effect on bleeding risk than physical activity.”

Disclosure: The researchers reported receipts of research grants, speaker fees, consulting fees, travel support and honorarium from Baxter Health Care, Bayer, CSL-Behring, Novo Nordisk and Pfizer.