Embracing the Unique

Previously printed in PEN, May 2018

When children are diagnosed with hemophilia, they are each given an essential diagnostic label: for example, hemophilia A or hemophilia B, severe, moderate, or mild. These labels originate from a lab analysis of the child’s blood. The diagnosis determines what type of factor replacement therapy each child will get. Labels like these can help draw a picture of who your child is and what he or she needs. But when it comes to dosing and prophylaxis regimen, sport choices and bleeding patterns, and even pain management, your child with hemophilia is unique. Diagnostic labels don’t adequately explain a person’s individuality and needs.

We asked parents from Facebook about their children with hemophilia: Has anyone ever used the labels of hemophilia to categorize your child, which resulted in limiting treatment options, or limiting what people think your child can do? What is it about your child that is not “typical” for someone with hemophilia? The responses poured in. While a child’s uniqueness may be revealed in a preference for certain sports or a physiological reaction to a particular product, most of the parental responses we received were about each child’s unique half-life, and about subsequent bleeding patterns.

Half-life was barely mentioned when my son was born. In the late 1980s and early 1990s, we dosed his factor using a chart based on his weight; it was very mathematical. We took one-half of his weight in kilograms times the factor level we desired, and this equaled the number of units of factor VIII we needed to infuse. Over time, as parents, we developed intuition about how much or how little factor our son needed based on his response to factor and his bleeding patterns, and we could adjust his dosage ourselves.

Up until about the last 10 years, hemophilia treatment centers (HTCs) often prescribed factor dosages based on weight, and determined a prophylaxis regimen based on a strict protocol from clinical studies. We now know that every child needs to have a pharmacokinetic (PK) or recovery study done to determine his or her individual, unique half-life response to a specific factor VIII product. Determining the unique half-life can help hone the amount of factor a child should receive, or indicate the best prophy regimen. A short half-life may mean more frequent infusions, higher doses, or the use of extended half-life products.

If anyone knows about the uniqueness of factor half-lives in children with hemophilia, it’s June Reese, who has four sons with hemophilia. She says, “One son has always had a short half-life and has really struggled with bleeds. His teachers often compare him to his brothers, one of whom never bleeds.” And this was a problem for the Reese family: in categorizing two brothers with textbook half-lives as “normal” for hemophilia, teachers dismissed the third brother’s frequent bleeds—they thought he was being careless, or worse, that he was imagining the bleeds.

Crystal Eskine has two sons with severe hemophilia A, ages 9 and 10. “I expected two similar stories,” she laughs. Despite having the same diagnosis as his brother, Crystal’s 10-year-old bleeds spontaneously, “if you look at him too hard.” Her younger son “never needs factor,” and “he isn’t even on prophy he bleeds so little!” When Crystal’s doctor wanted her to adhere to a traditional dosage and infusion schedule with her older son, her gut instinct told her it wasn’t good enough. She knew her children’s unique responses to factor. “I started giving my older son double doses. I took notes, showed our doctor, but he still he thinks I’m worrying too much, while I still don’t think the dosing regimen is good enough.” Crystal continues, “I’ve asked for a PK test, with blood samples taken over a much longer time period, but he has said no.”

And then there is Jen Miller’s five-year-old with severe hemophilia A. Jen calls him a “typical boy” who enjoys video games, swimming, T-ball, and playing with his friends. His

factor half-life is very short, which is not typical, but this doesn’t seem to impact his bleeding patterns.

When a shorter half-life does impact bleeding patterns, and parents instinctively know something isn’t right, they need to alert their HTC staff, sometimes to prove that their child does not fit a category or label. In these cases, parents should request a PK study. Crystal laments, “My boys’ hematologist makes me feel like I’m doing something wrong, but refuses to do a PK study.” June adds, “For years, our medical staff acted as though we were to blame when he’d have bleeds—even though he was infusing regularly.”

Kate Stotz, who has a 22-month-old with severe hemophilia A, felt she had to fight against the standard prophy infusion schedule of three times a week. “This was not working for our son,” she explains. “He was having frequent bleeds on Sunday, the day he was unprotected. Trough levels indicated that in order to maintain a minimal 1% trough, we could not exceed 48 hours between infusions.” Though Kate wanted to infuse every other day to keep him protected, her son’s hematologist didn’t want to break from the traditional schedule the HTC normally prescribed. “It took a lot of advocating on our part and ultimately finding a new doctor at a different HTC.”

Sarah Hueston successfully advocated for a new prophy regimen for her 16-year-old son with severe hemophilia A, who plays two varsity sports. When they determined he had a short half-life, the HTC team, Sarah, and her son developed his treatment plan together. He now infuses standard factor daily. “It’s what works for us,” says Sarah, “and his doctors are so proud of him, as are we, his family! Never did we think he’d be doing the things he’s doing even 10 years ago!”

By logging her son’s bleeds, Stacey Mollinet was able to convince her HTC team to change the treatment schedule. When her son with severe hemophilia A was a young teenager, he didn’t bleed like a typical severe and was not very active by nature. “I had to push the HTC,” she recalls, “so he could treat only twice a week, instead of a standard prophy schedule.” Around age 14, he started to bleed more like a typical severe. So Stacey worked with the HTC to adjust her son’s dosing schedule, and ended up dosing every other day until he switched to extended half-life factor two years ago.

“There’s not a one-size solution for everyone,” Stacey has learned. “Keeping good infusion and bleed logs so you know what schedule works best to prevent bleeding is important.”

Crystal laughs, “I could probably write a book about all the ways my boys ‘differ’ from the typical definition of hemophilia.”

And in a community where boys “typically” have hemophilia while women are carriers, women are now advocating to redefine what it means to have hemophilia. Labels have their place, but when we define hemophilia and determine treatment plans, we sometimes need to look outside the box at hemophilia—and trust the parents and patients when they describe their own uniqueness and needs.

Did you miss our May issue of PEN? Download it on our website today!

Introducing the new faces of Just B from IXINITY®

Who better to represent what it means to “Just B” with hemophilia than the people who are defining it in their daily lives? That’s why today, I’m excited to be one of the first to feature some of the new faces from our community who are joining the promotional campaign from Aptevo, makers of the factor IX treatment, IXINITY® [coagulation factor IX (recombinant)].

See Joe share more of his story.

See Nathan share more of his story.
 

Reference: 1. IXINITY [coagulation factor IX (recombinant)] prescribing information. Berwyn, PA: Aptevo BioTherapeutics LLC; April 2018.

 

100 Years Ago: Prince with Hemophilia Dies

This week is a very special: it’s the 100th anniversary of the death of the last Russian royal family, the end of the Romanovs. Special because not only did it lead to a massive change in world history, but it was also the death of the little prince with hemophilia, Alexis.

Hemophilia appears to have played a vital role in the story of the Bolshevik takeover of Russia, and subsequent spread of Communism. In Nicolas and Alexandra by Robert K. Massie*  Tsar Nicholas II, though not a very clever leader to begin with, is so distracted by his son’s suffering that he unwisely allows the “mad monk” and faith healer Rasputin to gain access to the inner circles of the royal family, while at the same time ignoring and not heeding the needs of his people for food and better quality of life. Rasputin is able to influence the course of events as Russia is battling the first World War, and yet also appears to have a calming effect on Alexis during his terrible bleeds.

There are no spoilers: everyone knows how this story ends. The entire family—Nicolas, wife Alexandra, daughters Olga, Tatiana, Anastasia and Maria, and son Alexis—was cloistered in Ekaterinburg under house arrest while the Bolsheviks take over. Although they are promised safe passage to England, where Nicholas’s cousin and doppleganger George V is on the throne, the family was instead slaughtered in the early morning hours of July 17, 1918. It was a horrific scene; the princesses did not die at once as they had about 18 pounds of royal jewels sewn into their clothing, to take to England with them.

Their bodies were eventually tossed down a mine shaft, which was not discovered until 1979, and even then not revealed until 1989, when the Russian archives were officially opened.

On August 15, 2000, the Russian Orthodox Church announced the canonization of the royal family. Alexis, the prince with hemophilia, would now be known as Saint Alexis.

And DNA tests would later reveal that the royal family, all the way back Queen Victoria, Alexis’s great-grandmother, had factor IX deficiency.

You can read more about this fascinating story hat changed word history by reading Nicolas and Alexandra, or one of many other books and on-line resources. I am happy to say that we are currently revising our children’s storybook called Alexis: The Prince Who Had Hemophilia, with new illustrations, done by a Romanian with hemophilia!

If you have hemophilia, this is a story you must know.

*The author is father of Bob Massie, currently running for governor of Massachusetts, who was born with hemophilia!

Camp Yes I Can… and I Will!

Five years sure went by fast. That was the last time I attended the Dominican Republic hemophilia camp “Yo Sí Puedo!” (Yes, I Can!). I don’t understand how the time slipped by, especially when I have such a deep attachment to the DR, which is only a 4-hour plane ride away. The DR was the first developing country I ever worked with, back in 1998, when there was no camp, and no factor. While Project SHARE supplied factor when we could, together with the fledgling Fundación Apoyo al Hemoílico (FAHEM) we created the DR’s first hemophilia camp. We were all new at this, so the first camp was a bit wild… but magical. While the camp grounds were trashed by Hurricane Georges, no one much minded when Red Sox pitcher Pedro Martinez, Houston Astros Moises Alou and Toronto Blue Jay Tony Fernandez showed up to autograph baseballs and play ball with the kids!

Those children I first met at camp are grown now, and many are serving as camp counselors. In fact, the one who was the quietest at that first camp, Brahian Valdez, is now the most extroverted, and has become Camp Director!

It was a joyous reunion in the parking lot of the Robert Reid Cabral Hospital in Santo Domingo. The teens were men, the little boys were teens, and a new generation of youngsters with hemophilia were present, wondering who this “gringa” was.

And then it felt like no time had passed. This was my ninth camp, so I knew everyone pretty well, except for the smallest ones and of course the newcomers. One of the joys of camp is that you get to see children grow and hopefully flourish through the years. While we have lost some to bleeds through the years, the majority are here, and have become best friends.

The theme was “Super Heroes,” perfect for this group. I could easily see during the four days of camp in the Lomas Lindas area outside of Santo Domingo that the older guys hobbled about on stiffened ankles, arthritic knees, and misaligned hips. The younger ones had no joint problems and dashed about madly, enjoying the excitement of camp and the freedom from their parents. After working with developing countries for 20 years now, this amazed me. Children without joint problems. Here, in the Dominican Republic.

Camp is now a highly structured program that mixes plenty of activities with quiet time and lectures for the 60 campers with hemophilia. Each day starts around 7; by 7:30 everyone is on the grass doing exercises, led by Cuchito, the coach. Blowing his whistle, Cuchito has the children stretch, do light exercises and then march in ever tightening circles, which ends in a crush and everyone cheering. Breakfast follows, which is always delicious. The food in the DR is superb! Then activities: it might be swimming in the pool, arts and crafts, or a game of ball that serves as teambuilding.

The pool is the favorite unstructured activity. Though they live on an island in the Caribbean, most of the children never get to spend time in water. The surf near the beaches in the capital is too rough. And the children come from very humble homes, where there is no access to a pool. Camp gives them a chance to enjoy water, which almost every child loves.

Camp founder Haydée de Garcia, who has an adult son with hemophilia, realized this and arranged for top-notch, young swim instructors to visit, and they gave each child swim lessons which mostly consisted of overcoming a fear of putting your head under water. Once that fear was conquered, the children enjoyed practicing floating and strokes.

The favorite activity, judging by the cheers and participation level, is wiffle ball. You must know that baseball is almost a religion in the DR! The DR sends more ballplayers to the US than any their country, and about 25% of all ball players in the leagues are from the DR. While we don’t use baseballs or softballs for safety reasons at camp, the kids and adults attack the wiffle ball as if it were! The games are exciting, loud, fun, funny and tiring!

This year we even had a bonfire just outside the camp facility, where we roasted marshmallows and everyone participated in some singalongs that ranged from traditional Spanish songs to rap!

A great presentation was made by Fendi, who was at the original camp in 1999. Wearing a Spider-Man mask, he talked about how the boys may have developed hemophilia: inherited, like WonderWoman; a mutation, like Wolverine; or acquired, like Storm. Very clever! And he stressed the need for community, like the X-Men, and proposed a program called Hermanos X (Brothers X), to keep this community strong.

The beauty of camp is abundant factor. Prior to about 2016 camp might be touch and go; you cannot have a camp if there is no factor, and the DR has struggled to get factor. SHARE always tries to assist and we stockpile factor starting in January for camp. A medical ward is set up before camp ever begins where everyone gets factor. This year? Everyone got factor prophylactically. How does that happen?

Well, we had our own superhero at camp this year. Bioverativ CEO John Cox visited the camp with his wife Ivette (who is Dominican) and his four children, to experience hemophilia camp in a developing country, and to see the results of his visionary idea (along with other visionaries; read about it here) to donate one billion IU of factor to the World Federation of Hemophilia (WFH) over 10 years. With this strategy, knowing there will be a steady flow of factor that doctors can count on, hundreds of children around the world in developing counties are now on prophy for the first time ever. These include “my” boys, here in the DR, here in camp. As I watched the older boys still hobble about, I watched the younger ones race and jump and climb, without fear, without arthropathy. It seems like a miracle, but it is in reality this vision come true—that with proper treatment, children with hemophilia can live full and active lives, in our countries and theirs.

The World Federation of Hemophilia, at Bioverativ’s request, donated all the factor to camp this year. No child had to worry about running out, which allowed them to run about!

And for the first time, WFH attended camp. Miquel Izquierdo, WFH regional director, arrived from Mexico to enjoy the camp—he himself has hemophilia! He fit right in and was beloved by all. He witnessed the great results of the factor donation, and also of Save One Life as about 16 enrolled beneficiaries attended camp, all looking great and doing well!

See photo gallery here.

We all loved having outside visitors, and next year, for our 20th anniversary, I am hoping to entice more volunteers from the hemophilia community to attend, to see the needs, the progress, to make connections. Despite the overwhelming success of camp, we can do more. Yes, we can… and we will!

From John Cox:

“I want to thank you and Presidenta Haydée Benoit de Garcia for including my family in hemophilia camp in the Dominican Republic.  We were so impressed with the camp and honored to be there. The Dominican boys were learning to deal with hemophilia in a poor country, and they were having fun too (the lively whiffle ball game was our favorite activity).  It was clear that this camp was something these boys looked forward to all year.  What struck me most was that Haydée and her counselors were teaching the boys to live a values-driven life no matter their circumstances.  Haydee’s leadership and her love for these boys — as well as yours, Laurie — is clearly impacting generations of Dominicans living with hemophilia. My children walked away believing in the camp theme “Yes You Can!” (¡Yo Sí Puedo!). Thank you for all you do, Laurie, and for the role of Save One Life in impacting lives in the Dominican Republic and around the world.”

Thanks to John Cox and family for spending family and vacation time with us, to the WFH and Bioverativ for the factor donation, to uniQure for gifts for the children, to Haydée and team, for another great camp!

See more photos here.

Amusement Parks and Summer Safety

This article was originally published in PEN, August 2002, Vol. 12, issue 3

Summer is in full force and with it, trips to theme and amusement parks. I’m a huge lover of them, including the thrill rides, like roller coasters. In 2000-2002 there were many stories and studies in the news about the potential for brain bleeds, and these were about people without bleeding disorders. Last year came the first reported case of symptomatic bilateral subdural hematoma associated with riding a centrifugal motion simulator ride. 

What does this mean for our kids (and big kids–adults!) who love to ride roller coasters and simulator rides? Have you asked your hematologist for his or her opinion? I decided to rerun one of my favorite articles from PEN 2002 about risks for kids with hemophilia at theme parks, written by Dr. Richard Lipton.

Summer is here, and millions of families will seek adventure and thrills at theme parks like Six Flags, Disney World or Universal Studios. What a wonderful day a family can have at a theme park! Kids and parents love the rides, water slides, entertainment and general excitement. Are there any special safety concerns or precautions for families with a child with hemophilia? Yes!

Think of a theme park as a very big playground, but with an atmosphere favoring less parental control—a setting that can lead to impulsive behavior by children.

Imagine yourself at a typical theme park. You’ll have general health concerns. Parks can be crowded, hot and sunny—so apply sunblock and drink plenty of water.

Theme parks have paved surfaces, harder than public playgrounds, and filled with children running. Your child needs to wear appropriate footwear. Flip-flops or Tevas might be suitable for water activities, but sneakers are safer for walking and running.

You’ll also have concerns specific to the theme park you visit. “Mind Eraser,” “Shockwave,” and “Nitro”—what about these special high-end rollercoaster rides? Riders are frequently subjected to changing speeds that result in “G-forces” similar to those experienced by trained, appropriately suited and restrained combat fighter pilots. Your child becomes “Top Gun” in shorts and a T-shirt! Parents should remember that any person can experience head trauma on these specialized rides.

How is the head affected by a ride like the Mind Eraser? Recall that your brain is surrounded by fluid; it is floating inside your skull. This arrangement cushions the brain, and reduces movement, protecting your brain from direct trauma and sudden shifts in skull position. It works quite well in our daily activities, and in automobiles (as long as we’re wearing a seatbeat). Now imagine speeding over the crest in a roller coaster. All of a sudden you’re weight- less, like an astronaut—this is called a Negative G- force. (You’ll have no trouble recognizing this moment, because every- body screams!) Then, after the coaster speeds down and resumes its climb, you feel your backside being pushed into the seat. It feels like the force of gravity has suddenly increased. This is a Positive G- force. Although your body is restrained, high G-forces could exceed the protective cushioning of fluid surrounding the brain, and could cause injury.

Interestingly, this year New Jersey became the first state to seek legal restrictions on the maximum allowable G-forces on amusement park rides. The regulations result from concerns raised by physicians about the association between neurologic damage and high G-forces on these rides. Certainly, such injuries occur very infrequently, but serve as a cautionary note to all riders of high-end roller coasters—with hemophilia, or without.

My advice? Take some precautions. Level the playing field by giving your child a prophylactic infusion of factor the morning of your visit to a theme park. Yesterday’s dose is not sufficient! Don’t wait until your child reports the symptoms of a bleed—it may be too late. Besides, your child is not going to report the flop he took running to the haunted house until you’re stuck in traffic on the long, long ride home.

Infuse first, then have a great time!

Dr. Richard Lipton was the physician in charge of the hemophilia treatment center at the Long Island Jewish Medical Center. As a United States Air Force Physician (1966–1968), Dr. Lipton knew several fighter pilots, who took him on “joy rides” (with lots of G-forces) that more than fulfilled his childhood fantasies. He is now retired.