Many parents of children with severe hemophilia rely on a formula that works most of the time: prophylaxis + other preventive measures = peace of mind. That is, until the child’s first breakthrough bleed occurs.
“With prophylaxis, you feel safe,” says Rita Gonzales, mother of a daughter and three sons, two of whom have severe hemophilia A. She is a National Hemophilia Foundation (NHF) Board member and served as president of the Lone Star Chapter in Houston for five years. “But when a breakthrough bleed occurs, you feel very vulnerable. All of a sudden you’re asking yourself: ‘What happened?’”
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The Prophylaxis Regimen
For people with bleeding disorders, the term “prophylaxis” refers to regular infusions of factor product to replace the missing or malfunctioning clotting protein in the blood. Although prophylaxis treatment has been studied for decades, it wasn’t until 1994 and the advent of safer blood screening measures and safer factor products on the market, that it became the recommended treatment regimen for children with severe hemophilia.
There are two main types of prophylaxis: primary and secondary. Both involve the regular infusion of factor VIII or factor IX to prevent joint damage in people with factor VIII deficiency—hemophilia A—or factor IX deficiency—hemophilia B. Primary prophylaxis typically starts in young children with severe hemophilia before the age of two years, before or soon after their first bleed. It is a long-term treatment that can be continued into adulthood.
Secondary, or “on-demand,” prophylaxis is a treatment for children and adults used to stop repeated bleeding into the same joint—called a target joint. On-demand prophylaxis is typically used to treat a bleed when it occurs, such as a breakthrough bleed. A third type of prophylaxis—short-term prophylaxis—is used in isolated situations, such as before participating in sports, a school field trip or prior to a dental or medical procedure.
NHF’s Medical and Scientific Advisory Council (MASAC) has placed its stamp of approval on prophylaxis. MASAC Document #179, “Concerning Prophylaxis (Regular Administration of Clotting Factor Concentrate to Prevent Bleeding)” states, “In view of the demonstrated benefits of prophylaxis (regular administration of clotting factor to prevent bleeding) begun at a young age in people with hemophilia A and B, MASAC recommends that prophylaxis be considered optimal therapy for individuals with severe hemophilia A and B (factor VIII or factor IX <1%).”2 The quantity “<1%” refers to the clotting factor level in the blood. People with severe hemophilia are often classified as individuals with less than 1% of the normal factor protein in their blood.
But prophylaxis isn’t perfect. Breakthrough bleeding can still occur between doses. “Frequently, prophylactic treatment is given two to three times a week, but individual infusion regimens may vary from once a week to every day,” says Lisa Michaels, MD, director of pediatric hemostasis and thrombosis at the UMDNJ-Robert Wood Johnson Medical School in New Brunswick, New Jersey. “Although the goal of prophylaxis is to prevent joint bleeds, breakthrough bleeding may not be completely prevented. If joint and muscle bleeds do happen, it is often on the ‘off’ days. Still, although prophylactic infusion helps prevent bleeding in people with hemophilia, it will not prevent bleeds that result from injuries or trauma.”
Symptoms and Signs of Breakthrough Bleeds
“The first breakthrough bleed is hard to recognize,” says Gonzales. “A four- or five-year-old will rarely say, ‘Mom, my ankle’s stiff.’ When you can’t put an explanation to it, you start questioning everything, from your parenting to the product to the regimen to the child.”
That’s when it’s time to call your hemophilia treatment center (HTC). “Until families become comfortable identifying bleeds, I usually want to lay eyes on it,” says Michaels. She examines the child “from stem to stern” to decipher whether the complaint is a routine scrape, a sprain or something more serious.
Michaels empathizes with the families in her practice who are unsure about breakthrough bleeds. If the child has been on prophylactic infusion for years, it may be hard for the parents to differentiate a breakthrough bleed from the normal everyday bumps and bruises. “For the parents, this is part of the education process,” she says. “They fear that they’ll miss a bleed—and they may miss the early signs—but my advice to them is: ‘You’ll know.’” Later on, as patients and families become more familiar with the different types of bleeds and their causes, they may be able to make their own treatment decisions.
With a child who is not yet talking, sometimes actions—or inactions—speak louder than words. Michaels says that symptoms of breakthrough bleeds include refusing to stand or bear weight, resorting to crawling despite being able to walk, limping or dragging a foot, cradling an arm close to the body, or showing a hand preference. Often these signs will precede the finding of swelling or obvious pain in a joint.
Common locations for breakthrough bleeds include ankles, knees and elbows. Breakthrough bleeds also can occur in deep muscles.
Older children often describe a breakthrough bleed as producing a bubbly or tingly feeling, says Jill Abrams, RN, MEd, at St. Christopher’s Hospital for Children in Philadelphia. “They tell us the area feels ‘funny.’” Some kids say that it feels like a pulled muscle. Parents may notice that the joint feels warm or hot to the touch; if there is swelling, the area may feel spongy.
Abrams says that while there are breakthrough bleeds that are related to trauma, there can also be spontaneous bleeds with no apparent cause. “We have one boy in our practice who has had repeated bleeds into his elbow at night while he’s sleeping,” she says. If appropriate, she often recommends elbow pads, knee pads and even helmets for children who develop bleeds while sleeping.
Cause and Effect
Besides doing a thorough exam in the office, your hematologist will probably ask you a series of questions to get at the root cause: Have there been any lifestyle changes since your last visit? Has the child had a recent growth spurt? What’s different?
Gonzales recalls that Damian, who has been on prophylaxis since he was a toddler, had a breakthrough bleed in his left ankle when he was in kindergarten. That year there were many changes for him. “He was in a new school with new friends who liked to play soccer—not chess—and he had a growth spurt,” she says. “He had gained 10 pounds. One of the tip-offs was that he was eating us out of house and home.”
Sometimes, the prophylaxis treatment dose needs to be adjusted due to weight changes. Since factor dose is largely dependent on the individual’s weight and the percentage of correction that is needed, any weight gain or growth spurt will have an effect on it. As the child develops, it is a good idea to routinely check the current dose with your HTC physician, especially at key intervals such as puberty.
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Another possible cause of breakthrough bleeds is the development of an inhibitor—an antibody to factor product. “We have a couple of patients in our practice whose factor levels, after an infusion, have not increased to the levels we anticipated,” says Abrams. “So we get an inhibitor level and perform a recovery study. Depending on the results, we would change their dose by increasing the units per kilogram or switch the child to a different recombinant factor product. If an inhibitor has developed, we would begin immune tolerance. For various reasons, we find that one brand of factor doesn’t work for all patients.”
Breakthrough bleeds can also result from inconsistent dosing on the home front. Sticking to a routine is difficult for adults and children, so missing a treatment here and there can happen, setting up the child for breakthrough bleeds. The importance of adhering to the dosing regimen cannot be overemphasized. It is vital to maintaining the proper level of factor in the child’s blood and of ensuring peace of mind for the entire family, especially when the child is away from home.
The treatment for breakthrough bleeds is typically administering factor product, usually two or three doses during the first few days after the bleed, says Abrams. One of NHF’s “Do the 5” National Prevention Program messages is: “Treat bleeds early and adequately.” For instance, if it is a deep muscle bleed in the iliopsoas muscle that flexes the leg, it may require bed rest for a few days.
Logging Information in the Log
Treatment logs are an important part of the information chain, from children to parents to the nurses and physicians at HTCs. Many HTCs will review the patient’s treatment log before prescribing more factors. Some insurance companies now require patients to maintain these logs for reimbursement of factor product. If you do not have a log, ask your HTC to provide one. It may prove to be more than just another record-keeping device.
Breakthrough bleeds may appear to be sporadic, but on closer inspection parents and providers tend to see the development of predictable patterns in some children on prophylaxis. “We have kept a log since Caleb’s first infusion when he was 18 months old,” says Candi Nakatani, of Redondo Beach, California, who is Caleb’s mother and a member of NHF’s First Step Task Force. “Caleb was on a Monday/Wednesday/Friday regimen, but would consistently get bleeds in the gap—late Sunday or early Monday. It took us about a month to see a consistent pattern.” After that, they switched to an every-other-day routine, which has diminished the breakthrough bleeding. Caleb is now nine and self-infuses through a port.
“I see some kids every Monday like clockwork—the same kids,” says Michaels. For her, one of the benefits of the home infusion log is that it helps pinpoint patterns that assist parents in determining when a bleed happened and why. “Sometimes it’s related to the increased activity level of the family over the weekend,” she says. “When that’s the case, bleeding events may be prevented by infusing on Fridays.”
For others, the bleed occurs during the week, when children are more active at school. “The factor product levels peak at infusion and decrease with time because of the half-life. On a day when the percent of factor product in the blood is lower, the child has a higher risk of a hemophilic bleed,” says Michaels. “For instance, if the kid is on routine prophylaxis, like Monday and Thursday, but the treatment log shows that most breakthrough bleeds occur on Wednesdays after gym class, then we have identified a need to change the infusion schedule,” she says.
Gonzales’ boys are 18 and 11, old enough to write entries in the spiral notebook that serves as their infusion log. “They take off the label from the factor product, affix it to the paper, then write the information under the columns for the date, time and reason for infusion,” she says.
For Gonzales, the log has already produced invaluable information. “When Damian had three breakthrough bleeds in a three-month period, we used the log to backtrack. It can help you see a pattern. It is absolutely the key to knowing the information and telling where target joints are developing.” While prophylaxis doesn’t guarantee complete prevention of breakthrough bleeds or total peace of mind, it does improve the child’s quality of life and long-term prospects for healthier joints.
“With prophylaxis, parents need to commit to a relatively involved process,” says Michaels. “They are taking on a substantial time commitment. It is hard enough for some families to get out the door in the morning; prophylactic infusion adds yet another thing that has to be done at the start of the day. But it provides the benefit of greater flexibility in planning family activities and the confidence that daily activities need not be limited by the fear of needing to stop and treat a bleed.”