Preventive treatment cuts bleeding rates in children with hemophilia A
Some youngsters may have a more severe bleeding tendency, study suggests
Written by |
- The researchers say their study was the first to assess starting preventive treatment before versus after joint bleeds in children with hemophilia A.
- The findings show prophylaxis reduces bleeding rates regardless of when treatment is started.
- Also, joint outcomes among all the children in the small study were mostly mild.
Routine preventive, or prophylactic, treatment reduces bleeding rates in children with severe hemophilia A, regardless of whether prophylaxis is started before or after significant joint bleeds occur, a small Brazilian study found.
Data showed that children in the South American nation who started preventive therapy earlier had fewer joint bleeds before treatment began, but higher overall bleeding rates. According to the researchers, this finding suggests these youngsters may have had a more severe bleeding tendency that led to earlier diagnosis and treatment.
Importantly, those who started preventive therapy later — undergoing so-called secondary versus primary prophylaxis — experienced more substantial declines in bleeding after treatment initiation, the researchers noted.
The team said their study “compared, for the first time, bleeding outcomes in [primary] vs [secondary prophylaxis] prior to and after starting” treatment.
Overall, “joint outcomes were mostly mild, with bone damage occurring only in [children with hemophilia A] under secondary prophylaxis,” the researchers wrote.
The study, titled “Outcomes of haemophilia A in children under primary and secondary prophylaxis: results from the HEMFIL Cohort Study,” was published in the journal Research and Practice in Thrombosis and Haemostasis.
Hemophilia A is caused by mutations in the F8 gene that result in a lack of functional factor VIII (FVIII), a protein needed for blood clotting. People with severe hemophilia A have an increased risk of recurrent and prolonged bleeding episodes, particularly into large joints such as the knees, ankles, and elbows. Repeated joint bleeding can damage the joints, leading to pain and movement problems.
Routine prophylaxis to prevent bleeds is generally recommended for people of all ages with severe hemophilia A. This is commonly done with factor replacement therapy, which provides a working version of FVIII.
Starting preventive treatment before the first or second joint bleed occurs — called primary prophylaxis — has been associated with better long-term joint health than beginning therapy after at least two joint bleeds have happened, which is known as secondary prophylaxis. However, few studies have compared bleeding and joint health outcomes between these two treatment approaches, the researchers noted.
Comparing primary vs. secondary prophylaxis
To learn more, a team in Brazil compared bleeding and joint health outcomes in 43 children with hemophilia A, all but one of whom had severe disease. Among them, 23 youngsters received earlier preventive treatment, while 20 were treated later. The data came from a subset of children included in a larger Brazilian research initiative called the HEMFIL Study.
Children receiving primary prophylaxis were diagnosed, on average, earlier than those receiving secondary prophylaxis. They also experienced their first bleed and started prophylaxis at younger ages, the team noted. High levels of inhibitors, a type of antibody that can interfere with replacement therapy, were more common in the primary prophylaxis group, the data showed.
Before starting preventive treatment, children in the primary prophylaxis group had a lower average number of joint bleeds per year than those in the secondary prophylaxis group (0.6 versus 2.0). However, their overall annual bleeding rate was higher (8.5 vs. 5.3), largely attributable to bleeds occurring outside the joints.
The researchers believe the data suggest that children who ultimately receive primary preventive treatment have more severe overall bleeding patterns, prompting “earlier diagnosis and prophylaxis initiation.” Still, that theory will require confirmation in future studies, the team noted.
Higher bleed rates seen among children diagnosed younger
After preventive treatment was started, bleeding rates declined in both groups. However, the primary prophylaxis group still had a significantly higher annual bleeding rate than the secondary prophylaxis group (7.3 vs. 4.5), the data showed.
Major bleeding rates declined in both groups, while children receiving secondary prophylaxis also had significant reductions in bleeds affecting the joints, skin, and mucous membranes. These children also had milder muscle bleeding.
Regardless of the treatment approach, bleeding rates declined over the course of the study, between 2013 and 2024. Both overall and joint bleeding became less frequent over time, reaching their lowest between 2022 and 2024. According to the team, this may reflect improvements in clinical management and greater awareness of the importance of prophylaxis in recent years.
Further analysis demonstrated that children diagnosed with hemophilia at a younger age had higher overall bleeding rates, while those who experienced their first joint bleed at a younger age also had higher joint bleeding rates.
[Preventive treatment] reduced the [annual bleeding rate] in both groups, with a more pronounced effect in the [secondary prophylaxis] group.
Joint health was similar between the two groups, as assessed using the Hemophilia Joint Health Score (HJHS), which looks for physical signs of joint damage, as well as musculoskeletal ultrasound, an imaging test that can detect structural changes that may not yet cause symptoms.
According to the HJHS, the ankles were the joints most frequently affected, followed by the knees and elbows. Crepitus, or a crackling or grinding sensation during joint movement, was the most common abnormal finding, the data showed.
Bone damage was detected in two children receiving secondary prophylaxis. However, because the scans were performed only once, when the children were approximately 8 years old, the researchers could not determine whether these changes developed before or after prophylaxis was started.
Overall, “this is the first data on outcomes of bleeding in [children with hemophilia A] under prophylaxis in Brazil, a middle-income country with the fourth largest population of people with [hemophilia A],” the researchers wrote.
The team found that preventive treatment “reduced the [annual bleeding rate] in both groups, with a more pronounced effect in the [secondary prophylaxis] group.”
The researchers noted, however, that because the study was small and involved patients from only a single center in Brazil, the findings may not be generalizable to a broader population.
Leave a comment
Fill in the required fields to post. Your email address will not be published.