hemophilia

Failure to Plan is a Plan to Fail

Michael Joshua

I’m so excited that the time has finally come for me to be in college, on my own, making my own decisions without direct input from my mom. However, I can still hear her advice even when she is not around. 

  1. Contact campus emergency, not 911.  The officer on duty was able to access my emergency plan.  She called an ambulance and provided me with a taxi voucher to return to campus once I was discharged from the hospital.  I left the campus via ambulance at 1:00 am.
  2. My hematologist spoke directly to hospital personnel in the emergency room and they were expecting my arrival. Unfortunately, the medical staff was not very familiar with hemophilia.  However, I remembered my mom always stressed the importance of me being knowledgeable enough about my diagnosis to be an advocate for myself. I was able to instruct the nurse on how to mix and infuse the factor.  The nurse had orders for an x-ray and to draw factor levels.  I remember a situation when I was younger that the ER staff wanted to draw factor levels and my mom refused.  I agreed to the x-ray.  I expressed to the nurse that I infused on a prophylactic schedule and checking levels immediately following that type of trauma was not necessary.  They also wanted to keep me overnight for observation.  I did not want to stay overnight at a hospital for a toe injury so I told the nurse that 24-hour observation was not necessary and I would be willing to sign anything she needed refusing their recommended treatment.  It felt so empowering to make a decision alone about my treatment.
  3. I was discharged from the ER and returned back to campus at 3:08 am.  When I called my mom couldn’t believe that I had been transported to the ER via ambulance, treated and returned back to campus in two hours.  Modified attendance is part of my academic accommodation so before I went to sleep, I emailed my instructors to inform them that I would not be in class the next week.  The office of accessibility was also contacted because my injury resulted in difficulty walking and my dorm room is located on the 9th floor.  When I woke up it was 1:30 pm.  I was contacted by the director of food service about my meals and my meals were delivered to my room.
  4. Not only did my accessibility counselor follow up with me, but my mom informed me that because she has permission to discuss my records, she was also contacted and informed of the incident.  My counselor asked if there was anything else that could be done to assist me.

Well, I had a bleed at school that required emergency treatment.  Not only was it a school holiday but it was in the middle of the night, 12:50 am to be exact.  As I was doing some strength training in my room, I injured my toe.  The entire foot was swollen in a matter of minutes, I was in extreme pain and could hardly stand.  Of course, my first reaction was to infuse but I wasn’t able to administer hardly any of the dose (my veins kept blowing).  As I sat on my bed, I decided to call my mom.  Not for her assistance but just to let her know what was going on.  She has always said that she prefers to be in peace, not pieces.  In other words, try not to make her worry any more than she already does.  After speaking to her, I called my hematologist.  We decided that going to the emergency room was necessary.  I called my mom back and informed her of the next steps.  She reminded me of the emergency plan that was put in place during orientation with the office of accessibility.  There was nothing for me to figure out.  I just followed the plan. 

Planning ahead and having a documented emergency plan in place was well worth the effort.  The plan was followed as written and most of all, the plan worked.  This incident confirms, “I have hemophilia; hemophilia does not have me”!

Michael Joshua, age 19, is from Baton Rouge, Louisiana. He attends Loyola University of New Orleans. My major is political science; he intends to become a successful lawyer.

Lights, Camera…

It’s our 30th anniversary! And since I am stuck at home like 90% of America, I’ve had few distractions and plenty of time to review tons of media from the past 30 years. My book “Raising a Child with Hemophilia” was published in 1990, when I was 33 years old. Armour Pharmaceutical Company wished to promote the book, and I found myself suddenly on TV and doing radio interviews, sometimes scheduled at midnight. The company hired a PR firm to work with me. We traveled to Cleveland, Dallas and Philly to make videos and promote the book. And some hemophilia nonprofits also included me in their promotional videos about hemophilia. It was a whirlwind time! I had two small children at the time, more books to create in the pipeline and a newsletter to produce, all done from home.

Guess what I found? Copies of the interviews and tapes. If you’d like to see them, go to our home page, click on “See” which will take you to our gallery, and click on “Videos.” You’ll see videos from the 1990s!

I did learn a few things: I never really liked giving interviews. Maybe it was just that I was always distracted with raising children and work (now I don’t mind at all). And when the PR firm thought it was a good idea to plug the product my son was using, I ended the corporate-sponsored interviews. It was interesting, to say the least! But I never went back on my personal policy of never personally endorsing a product. Enjoy the shows!

Hemophilia B: Her Voice, Her Life

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This is a paid public announcement from Pfizer and does not constitute an endorsement of products or services. When you click on the links in this blog entry, you will be direct to a Pfizer website LA Kelley Communications always advises you to be a savvy consumer when contacting any company; do not reveal identifying information against your will.


Prepare for Big Changes

When we use the word “transitions” in hemophilia, we normally think about our child’s life cycle (or our own) and how it impacts healthcare: Children transitioning into adulthood at age 18 need to see an adult hematologist, not a pediatric hematologist. Adults finishing college or trade school need to transition into the workforce. Adults at age 26 need to transition off their parents’ health insurance. We may have joint issues as we age.

But we can also view transitions as something happening to hemophilia treatment, because that has a life cycle too. And right now, hemophilia treatment is undergoing massive, rapid change. New products, novel therapies, and gene therapy…can the US market of roughly 20,000 with hemophilia support all the products? Will insurance cover them all?

A Look Back: Our Infancy

If we accept that hemophilia treatment has a life cycle, let’s look back at its infancy and development. Early treatment for hemophilia involved whole blood transfusion and later, human plasma. Fresh frozen plasma (FFP) allowed treatment to be stored and then thawed when needed. Whole blood and FFP were both only marginally effective at controlling a bleed, due to the low level of factor VIII and large volumes that needed to be infused. Then, in the mid-1960s, came cryoprecipitate: rich in factor VIII, and created from thawed human plasma. Its higher factor VIII level in a smaller volume made administration easier, faster, and more effective.

A breakthrough came with commercial clotting factor concentrate in 1968, made from donated human blood or blood plasma. This new plasma-derived concentrate was freeze-dried and reconstituted with water when needed. Factor in a bottle! Now treatment could be done at home or away, freeing patients to travel and live more normal lives. Infusion time was tremendously shortened, meaning treatment could stop bleeding faster, reducing pain and helping to prevent joint disease. But these early factor concentrates were not treated to inactivate viruses. Tragically, in the late 1970s and early 1980s, contamination of the nation’s blood supply from donors infected with HIV, hepatitis C, and other viruses meant that clotting factor was also contaminated. Thousands of people who had hemophilia and used factor concentrates were infected and died.

In the mid-1980s, a new stage in the life cycle of hemophilia treatment emerged: the creation of factor that was virally inactivated. Viral inactivation processes, such as heat or solvent/detergent wash, could destroy the fragile HIV. Today, all clotting factor is considered safe.

The deaths of so many led to another groundbreaking stage in the life cycle of hemophilia treatment: recombinant clotting factor. Recombinant factor is produced in a lab, using human genes that are inserted into genetically altered mammalian cells. In 1992, the first recombinant factor VIII clotting factor product (Recombinate, manufactured by Baxter) was approved by the FDA. In 1997, the first recombinant factor IX product (BeneFix®, manufactured by Genetics Institute) entered the market. And now? There are now about 20 recombinant factor products on the market to treat hemophilia. We’ve come a long way.

The Family Expands: Crying for Attention

Why so many products? There are some things to know about the factor market. First, the US is the largest market. Not in population—that would be China. But in dollars. Estimates are $4.6 billion annually.1 This lucrative market attracts competitors. But factor products are protected by patents. So to avoid patent infringement, changes or improvements are made to products, making them slightly different. Some of these changes have involved production processes; and the quest to remove unnecessary human and animal proteins gave us “generations” of recombinant factor products.

Now we have three recognized generations of factor products: First-generation products use animal blood proteins in the cell culture medium, and add human albumin, a blood protein, to the final formulation to stabilize the factor. Second-generation products stabilize the factor with sucrose, not albumin. Third-generation products use no added animal or human proteins, either during processing or in the final formulation.2 Today, all factor products except for Recombinate and Kogenate® FS are third generation. A special shout-out to Octapharma’s Nuwiq®, a recombinant factor VIII product that uses a human cell line instead of an animal cell line in its production process.

Recombinant products, by reducing the potential for viral transmission, are an improvement over past products. And yet first-generation products remain in use, as do plasma-derived products. So far, there seems to be a purpose and a place for all products.

Growth Spurt!

But consumers want more. Researchers found ways to keep infused factor circulating in the body longer, by extending its half-life—meaning fewer infusions and less burdensome treatment. Eventually, extended half-life (EHL) factor was created. After a relatively calm 10 years in the marketplace with what is now called “standard half-life” or just “standard” factor, EHL factor came along, resulting in a big growth spurt in the life cycle of hemophilia treatment. Hailed as the next best thing, EHL factor was and still is heavily promoted. Biogen created the first two EHL products, which were soon followed by EHL products from Baxter (now Takeda), Novo Nordisk, Bayer, and CSL Behring.

  The creation of EHL products seemed like the exciting, wild teen years for our community. Children with hemophilia lived even more normal lives, without infusing so often. Freedom!

Family Feud

In the midst of this growth spurt and innovation, some major shifts were taking place in the hemophilia marketplace. Companies were separating, divorcing, getting married, taking on lovers, adopting other products. Baxter split off its biological division (which made its factor products) to become Baxalta. Genetics Institute was bought by Wyeth, which was then bought by Pfizer. In the early 2000s, Bayer had divested its plasma division, which became Talecris. Then Grifols bought Talecris (you can still see the primary color bar on the Koate®-DVI box, the same bar that appears on Kogenate FS). Biogen, soon after launching its groundbreaking EHL products, suddenly divested its hemophilia group, which became Bioverativ. Soon after the new sign was up at Bioverativ’s headquarters, it was bought by Sanofi Genzyme. Baxalta must have been a very attractive mate, because soon after it was spun off by Baxter, it was snatched up by Shire, an Irish pharmaceutical company. Just when everyone was getting used to Irish brogues, Shire was purchased by the Japanese company Takeda, a pharma titan.

 Perhaps no products have changed hands more than those of CSL Behring, starting in the 1980s, when it was Armour Pharmacuetical. And although CSL Behring has remained the parent company since 2007, it has recently abandoned some hemophilia products: Helixate® FS and Monoclate-P®. Its focus is now on EHL products only for hemophilia.

And this is the concern for the future life cycle of hemophilia treatment: Can the market sustain 20 recombinant products? Which products will be removed next from the marketplace? Will product change come from the consolidation of companies buying each other and reducing overlapping product lines? Will it come from flagging sales, if one product dominates the market? Or will product change come from a novel treatment—using no factor at all?

Newest Child

One product getting a lot of attention these days is the newest addition to the family—Hemlibra®, a nonfactor antibody product that mimics the action of factor VIII in the body. It’s used for prophylaxis in people with hemophilia A and inhibitors, and in those without inhibitors. The product’s clinical success has many patients cheering on Facebook, some advocates cautioning consumers to wait and see, and some doctors already prescribing it for newborns. Hemlibra is called a “market disruptor” for a reason. It’s created a whole new way to treat hemophilia: with weekly to monthly subcutaneous injections. And people with inhibitors are reporting no bleeds for weeks, even months in some cases. Will factor concentrate still be needed? Read Wendy Owens’s feature article in this issue to learn the answer!

The life cycle of hemophilia treatment has entered a new phase, perhaps similar to young adulthood, where there are many options, and our community has been educated and prepared. We’re ready for greater independence from this disorder, and ready to live life more on our own terms.

But like all young adults, we still need advice from our elders, from our blood brothers, from our physicians. And we need to do our own homework. We need to read about current products and new ones that will enter the marketplace. Do you feel informed enough to choose? Will your insurance cover all the new products? Will you switch to another product, if one day your insurance company no longer covers yours?

 Stay in touch with the life cycle of hemophilia treatment: name changes of the corporate players, which products belong to whom, and especially, the manufacturer of the product you use. Decisions at the top—by government, by corporations, and by insurance companies—may eventually impact your choice of treatment.

We have more freedom and more choices than ever before, but we need to exercise responsibility, by learning all we can. Because one thing is for certain: we are only in the young adult stage of hemophilia therapy. Prepare for more growth and more change.  It’s coming.

  1. Mark Terry, “A Look at Hemophilia Drug Prices and the Market,” biospace.com, July 3, 2018 (accessed June 2, 2019).
  2. Recombinate is a first-generation recombinant product. Kogenate FS is a second-generation product. Advate, Adynovate, Afstyla, Alprolix, BeneFix, Eloctate, Idelvion, Ixinity, Jivi, Kovaltry, Novoeight, Nuwiq, Rebinyn, Rixubis, Vonvendi, and Xyntha are third-generation products.

Bubba’s Outcome

Part 3

Bubba did start to wake up, and that made us very happy. He opened his eyes and was almost immediately able to focus on Ashley. That made us happy too. Then he made a very unhappy face, an incredibly unhappy face.

He started sniffling. Then he started crying.

We were a bit concerned.

The crying got louder. The crying began to include screaming.

We didn’t have the slightest clue what was going on. What was wrong? Did his chest hurt from the surgery? Was he scared because he woke up somewhere new?

Let’s take a break for a learning experience. You may or may not be aware that some small children have an adverse reaction to anesthesia. The reaction does not occur when they are initially anesthetized; it happens when they wake up. It’s called emergence delirium.

The attending nurse reassured us that this was not uncommon. She did acknowledge that it was difficult. I’m sure she’d seen more than enough parents come through and experience angry kid syndrome upon waking. We were also told that they could give medicine prior to surgery that would decrease the severity of this reaction.

The whole process lasted about 15 minutes. Bubba slowly calmed down and began to resemble the child we sent into surgery, not the angry little monster that had emerged into the recovery room. He was obviously exhausted. All of us were ready for it to be over. We were cleared to head back to his room.

Bubba had made it through the surgery and we were good to go. The reaction to coming out of anesthesia was actually minor in the grand scheme of things. Ashley and I were on our way to becoming more active in the role of Bubba’s care. With the port in place we’d be trained how to infuse him at home. All of the stress that we were currently experiencing would be more than worth our troubles in the end.

The true test would come when it came time to test the port. Being a medical newbie, I had no idea how complicated or how simple this process would be. Bubba would be given sufficient time to rest, but we all knew that a functional port was the only path to us getting home.

Later, I joined three nurses in an exam room located right down the hall from our hospital room. It might have been a procedure room. The combination of fluorescent lighting and white overload made the room incredibly uncomfortable.

The goal was to ensure that Bubba’s port would function properly so we could determine how much time he’d need to remain in the hospital. The nurses were upfront and honest about the fact that he would not react favorably to this process.

My job would be to help hold Bubba still and do my best to calm him. I wanted to do my best on both fronts. He remained accessed because the surgery site would be far too sensitive to access with a new needle. Our goal was simply to connect a line in and make sure that everything could be pushed with no problem.

Bubba is accessed, so the nurse is now ready to push saline as soon as she gets blood return.

No blood return. That’s fine. Ports can be finicky. She tries again. No blood return. Not a problem, we’ll just put his arms above his head and that’ll open things up. A pattern began to emerge. The nurse could not get blood return.

Bubba was rolled onto his side.

Bubba was allowed to sit up.

We maneuvered and finagled him around trying to get blood return. Each time the nurse drew back the plunger nothing happened.

Bubba was getting angry. He got even angrier as the nurses tried to adjust the needle that was used to access the port. Any form of sedation or local anesthetic had worn off quite some time ago. He was now a one-year-old with a needle being moved around in his chest.

The noises started as intermittent crying. The intermittent crying became more constant. The crying was then joined with some attempts to get out of our grip. My willingness to keep him on the table was beginning to fade. I just wanted to pick him up and get him out of the room. Bubba soon began screaming at the top of his little lungs. His face was soaked with tears and bright red in color.

The issue with the port simply added to our emotional ups and downs. We began as parents frightened because their small child needed surgery. The emotional upswing came when we thought about more effectively managing his condition. We were scared to death when he went back for surgery and elated when he came out. My spirits hit rock bottom again when I went back to the room to tell Ashley that the port was not functioning.

It was not long into the day when a physician approached us.

A gaggle of short white-jacketed medical students were in tow. To be completely honest my first thought was, “Ugh.” The last thing I needed was the medical neophytes peering over us as the actual doctor spoke.

The physician explained to us that it was clear the port was not functioning.

The x-rays that they’d taken showed the line from the port was pushed up against the wall of the vein. This meant that there wouldn’t be any blood return. The opening on the end of the line was simply sucked up against the wall of the vein.

The med students continued to hover. I began to fume.

We were informed that the line would need to be moved in order to make the port functional.

“So, will he need to have another surgery?” I asked in a noticeable irritated voice.

The physician answered yes.

“So, the first surgery was done incorrectly and now he has to go in again?”

This is the type of time that my wife would often describe as “Derek acting like an ass.”

I should have been more aware that there was no reason to be angry with the surgeons. They were trying to thread a line into the body of a baby. That cannot be an easy task.

The physician calmly indicated that the line placement was not optimal and that Bubba would need to have another procedure. They wanted to schedule surgery as soon as possible. The surgeons would be able to use the existing incision.

We ran into one major issue: clotting factor.

There was none. You can’t operate on a hemophilia patient unless they’re factored up. Without available factor, there would be no surgery.

We were fortunate to have an incredible point of contact for our specialty pharmacy. Her name was Julie and she was aware that we were headed to St. Louis for Bubba’s surgery. In fact, she had given me her personal cell phone number in case anything happened. It didn’t really register at the time that the number might come in useful.

Our nurse told us that it could be a few days before they could be restocked.

I was not ashamed to call Julie. As expected, I didn’t get her at first. She probably saw a weird number come up on her cell and didn’t feel like hearing about her car’s expired warranty.

… and then Julie called back.

I explained what was going on and how we were certain she was a factor wizard who could make our necessary medication appear with the wave of a wand. Problem number one was that the pharmacy could not ship to the hospital. We found out that insurance would cover having Bubba’s factor shipped to us in St. Louis. We’d just take possession and then hand it over to the physician.

Julie was awesome and, I imagine, is still awesome. I doubt she’ll every read this article. If she does, Julie you are a superhero in the eyes of the Markley family.

We made one major change. Bubba was given medication prior to surgery that would help us avoid him turning into a screaming little devil spawn when the anesthesia wore off. We had faced enough challenges in a short time and there was no reason not to stack the deck in our favor in any way we could.

The outcome this time was far better. Surgery went quickly, Bubba did not awake yelling and crying, and we were able to ensure that the port was functional. Our emotional rollercoaster had finally come to a gentle stop instead of catching fire, going off the rails, and slamming into an animal shelteer filled with kittens. Things were much better the second time around.

Now the work would begin. Ashley and I would be trained to administer factor twice per week via Bubba’s new port. A new chapter in our life had begun!

Derek Marley lives in Saltillo, Mississippi with his wife Ashley and their children Abbey and Bubba. He is the executive director of two University of Mississippi regional campuses and an assistant professor in the school of education. Ashley is a fourth grade teacher in the Tupelo Public School District. Derek is author of The Bubba Factor, which can be ordered on Amazon.com.

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