Summary
A patient was experiencing severe knee pain. Unfortunately, this wasn’t anything new. For decades, he’d been suffering from joint disease, caused by severe bleeding in his knees from a rare blood disorder — hemophilia A. The patient was born in the 1960s, a time when the life expectancy for patients with hemophilia was only 10 years. But as Dr. Annette von Drygalski, a board certified hematologist and the director of the Hemophilia and Thrombosis Treatment Centre at the University of California, San Diego, explains, advances in hemophilia treatment throughout this patient’s life allowed him — and many others like him — to live a longer, richer life.
Annette von Drygalski, MD, PharmD, RMSK
Professor of Clinical Medicine
Director, Hemophilia and Thrombosis Treatment Center
University of California
San Diego, CA
Annette von Drygalski is a Professor of Clinical Medicine in the Division of Hematology/Oncology, and Director of the Hemophilia and Thrombosis Treatment Center, Department of Medicine, at the University of California, San Diego.
Dr. von Drygalski earned her pharmaceutical and medical degrees from the Ludwig Maximilians University, Munich, Germany. She completed residency in Internal Medicine at the Medical College of Wisconsin, Milwaukee, and fellowship in Hematology and Oncology at the University of California, San Diego and The Scripps Research Institute.
Dr. von Drygalski is dedicated to the care of patients with hemophilia and other bleeding disorders addressing the evolving needs of aging patients with hemophilia, such as new therapies, cardiovascular disease and hypertension as well as the progression of hemophilic joint disease. In this role, Dr. von Drygalski investigates gene therapy and other novel molecules in clinical trials, and elucidates effects of new treatments on the pathobiology of joint health, both at the bench and in translational studies. Dr. von Drygalski has pioneered musculoskeletal ultrasound for rapid joint bleed detection and joint evaluation in hemophilia. She is certified in musculoskeletal ultrasound by the American Registry for Diagnostic Medical Sonography, and has developed the Joint Activity and Damage Exam (JADE), a validated ultrasound protocol to quantify synovial and osteochondral changes as well as inflammation in the hemophilic joint. She is also the Director of the CME-accredited course “Musculoskeletal Ultrasound in Hemophilia” at the University of California San Diego.
Dr. von Drygalski also developed a focus in international outreach to afford training for hematologists from developing countries and establish care for patients with hemophilia and bleeding disorders in Mozambique, as well as address mortality from post-partum bleeding.
Transcript
DDx SEASON 9, EPISODE 1
The Ups and Downs of Hemophilia Treatment
Dr. Raj Bhardwaj: This season of DDx is sponsored by Sanofi. The case study you’re about to hear is a real patient story.
In 2010, a man in his late 50s explained to his doctor that he was having severe knee pain.
Unfortunately, this wasn’t anything new for this patient.
For decades, he’d been suffering from joint disease caused by severe bleeding in his knees.
And that’s because he was born with a rare blood disorder — hemophilia. When he was a child in the 1960s …
Dr. Annette von Drygalski: … the average life expectancy of a child born with hemophilia was about 10 years. Children died of the disease because there was nothing available that could really save them from life threatening bleeding.
Dr. Bhardwaj: This is DDx, a podcast from Figure 1 about how doctors think.
I’m Dr. Raj Bhardwaj.
This season, we’re taking you inside the minds of doctors who specialize in the most common type of hemophilia, hemophilia A — an inherited bleeding disorder that prevents the blood from clotting properly.
Today’s case is from Dr. Annette von Drygalski. She’s a board certified hematologist and the director of the Hemophilia and Thrombosis Treatment Centre at the University of California, San Diego.
Dr. von Drygalski has been compensated by Sanofi for her participation in this episode.
CHAPTER 1 — CASE STUDY
Dr. Bhardwaj: Our understanding of hemophilia — and its treatment — has evolved dramatically over the last few decades.
And that’s had a life changing effect for many folks with this disorder.
But even when you’re headed in the right direction, there can still be unforeseen hiccups and complications.
In the 1960s and early 70s, treatment was very rudimentary.
Like most children with hemophilia at the time, Dr. von Drygalski’s patient had to be rushed to the hospital when he got a bleed.
Dr. von Drygalski: When this patient was really young, he had probably whole blood transfusions. There was nothing available that could really save them from life threatening bleeding.
Dr. Bhardwaj: Transfusions replaced the blood he lost and helped stop his bleed, but it didn’t protect against future bleeds.
In the 1970s and 80s, treatment began to improve.
Researchers discovered that people with hemophilia were missing something in their blood that helps it clot — proteins called factor VIII (8) or factor IX (9).
People with mild or moderate hemophilia have reduced levels of factor VIII or IX in their blood. Someone with severe hemophilia A, like Dr. von Drygalski’s patient, has extremely low levels of factor VIII activity, if any at all.
Dr. von Drygalski: It was then recognized that these missing clotting factors, factor VIII or IX, are contained in plasma, and so plasma infusions provided that clotting factors.
Dr. Bhardwaj: This discovery meant doctors could give plasma instead of a whole blood transfusion.
It was a breakthrough. But the emergence of a deadly new virus was about to cause a major setback in the management of hemophilia patients.
One day, shortly after receiving a plasma infusion, Dr. von Drygalski’s patient started to feel sick.
Dr. von Drygalski: Some of these plasma products, unfortunately, got contaminated with HIV and this patient, like so many others, found out about the HIV infection after they had been using these plasma preparations and they got sick, and then, did an HIV test when HIV testing became available and learned about their diagnoses.
Dr. Bhardwaj: Unfortunately, more than 4,000 people, roughly 40% of all people with hemophilia in the U.S. in the early 1980s, died from contaminated blood products that came from infected donors.
Dr. von Drygalski’s patient was one of the lucky ones. He received treatment and was able to maintain an undetectable viral load.
But even though he was able to manage his infection, years of bleeding into his knee left him with severe joint damage and chronic pain.
But in the early 1990s …
Dr. von Drygalski: He was on crutches, unable to move around a lot, the patient had difficulties motoring around being in their own home. If there are stairs involved or just getting out of bed in the morning, getting dressed, and getting to a job. It’s really hard to hold a regular job or work. Just leaving the house is problematic.
Dr. Bhardwaj: His options were limited. So, at just 30 years old, he was forced to get a knee replacement.
His mobility improved.
Soon after, another new therapy became available.
For the first time, Dr. von Drygalski’s patient had access to a lab-engineered, clotting factor.
This new treatment eliminated the risk of blood-borne infections like HIV and allowed him to infuse at home.
But even with this safer and more convenient treatment, he could still only treat a bleed after it occurred.
There was no preventative measure available so his joints were still at risk.
Before long, his knee was in trouble again.
Dr. von Drygalski: After joint replacement surgeries in patients with hemophilia, there is a higher infection risk. This patient was bogged down with infections. With a lot of blood showing up in the joint, you also have lots of maybe bacteria or other microorganisms that would usually maybe not reach the joint.
Dr. Bhardwaj: But another big turning point in hemophilia treatment was just around the corner.
By the mid-2000s, preventative, prophylactic treatment became available.
This was a game-changer. For the first time, this patient could prevent bleeds before they happened.
But prophylaxis couldn’t reverse the damage already done.
When Dr. von Drygalski met her patient; he had crippling arthropathy, or joint disease, in more places than just his knee.
Dr. von Drygalski: He had severe arthropathies in all six joints; ankles, elbows, and knees. But one of his knees had received two knee replacements and unfortunately, developed breakthrough bleeding in that affected knee.
Dr. Bhardwaj: Prophylactic treatment slowed the progression of his arthropathy. He was experiencing fewer joint bleeds than ever before.
But they still happened from time to time.
Dr. von Drygalski: This patient came in, he felt he has bleeding. The knee was very swollen. We saw it on the ultrasound like 100 ml or so, a lot of blood that we pulled out of those joints. Yeah, it’s very painful.
Dr. Bhardwaj: Another small evolution in hemophilia care came in the form of longer lasting treatments.
When Dr. von Drygalski’s patient first started on a prophylactic regimen, he had to infuse using an IV four or five times a week.
This newer treatment reduced that to two or three times a week.
Dr. von Drygalski: That may not sound huge, but for the patient that was huge because it gives them the freedom of more activity, of peace of mind, of having to worry one less day about infusion and giving them some peace of mind in terms of bleed protection.
Dr. Bhardwaj: That treatment worked great for a few years.
But the arthropathy in his elbows was getting worse, making it difficult to self-infuse, even at this reduced frequency.
Not only that, it also made it difficult to practice his passion.
Dr. von Drygalski: So this patient learned to play the guitar and, become a musician, but then he has elbow problems, and that became harder over time. It is terrible because it takes away things you really love to do.
Dr. Bhardwaj: To make matters worse, decades of bad bleeds made it challenging to find healthy veins for self-treatment.
So Dr. von Drygalski had to explore other, less than ideal, interventions.
Dr. von Drygalski: I think it became clearer and clearer that he simply couldn’t infuse as much anymore so we discussed PICC line insertion, which is IV access that goes close to the heart. But of course you always have a dangling line. It’s hard to shower, so you have to pack it up. It’s not a long-term solution that’s really feasible and also it’s prone to infection. So that wasn’t an ideal option.
Dr. Bhardwaj: Then, hemophilia treatment made another leap forward.
A weekly injection, administered like an insulin shot, became available that was much easier to self-administer than an IV infusion.
Also, at only one dose per week, this new treatment lasted considerably longer than previous prophylaxis with factor VIII therapies.
Dr. von Drygalski thought she’d found her magic bullet.
It worked perfectly for a time but the patient’s joint bleeds eventually returned.
Once again, they were stuck.
Dr. von Drygalski: But then, very happy to say, came the advent of a new clotting factor preparation and although IV, once weekly IV is doable, providing a high level of protection through most of the week for this patient. He sets himself up, takes a lot of time, takes the one vein that’s available. And it’s doable even with these bad elbows.
Dr. Bhardwaj: And it’s made all the difference for this patient.
Dr. von Drygalski: He is very happy because no more bleeding for the last I’d say six months since he switched. And that’s huge. So he’s very happy, at least in his daily activities, what he can do — getting out of bed and getting around in his apartment and going out shopping and doing relatively normal things without fear of bleeding again.
Dr. Bhardwaj: Working with people who suffer from hemophilia has been a source of inspiration for Dr. von Drygalski.
Dr. von Drygalski: They are always looking forward, trying to find a positive angle, take on the next thing, overcome hurdles, never sort of giving up. That’s a very rewarding aspect for myself.
CHAPTER 2 — LESSONS
Dr. Bhardwaj: 60 years ago, the majority of people with hemophilia died in childhood or early adulthood. Today, the life expectancy of someone with hemophilia is similar to the general population — they’re able to lead full and relatively normal lives.
There are more, and better, treatment options than ever before.
And that’s armed physicians and their patients with something very important — choice.
Dr. von Drygalski: Having now treatments available to pick from is huge because it allows to work with the patient on individual solutions and that has never been like that, this is just all coming to fruition.
Dr. Bhardwaj: Dr. von Drygalski says it’s important for doctors to know what resources they have at their disposal so they can provide customized solutions based on the unique needs of the folks they care for.
Dr. von Drygalski: Doctors should be aware if they encounter hemophilia patients that there are specialized federally funded centers. They should ensure that patients have access to these centers and at the same time, really liaising with that hematologist at that center to manage in a mindful way, the other comorbidities, which could be HIV or hepatitis infection, perhaps that is progressive arthropathy, so, paying attention to comorbidities because it requires an individualized approach.
Dr. Bhardwaj: Hemophilia treatment has come a long way since Dr. von Drygalski’s patient was born in the 1960s.
In the past, physicians had very limited treatment options for patients with hemophilia. Sometimes, they even had to forgo important care for other health issues if it could increase the risk of bleeding.
Today, doctors have more flexibility than ever before.
Dr. von Drygalski: And, one shouldn’t just consider, “Oh, the patient has hemophilia, so therefore, I can’t do all of these other treatments.” No. The landscape has really changed and we need to talk.
Dr. Bhardwaj: Thanks for speaking with us Dr. von Drygalski.
This is DDx, a podcast by Figure 1.
Figure 1 is an app that lets doctors share clinical images and knowledge about difficult to diagnose cases.
I’m Dr. Raj Bhardwaj, host and story editor of DDx.
Head over to figure1.com/ddx, where you can find full show notes, photos, and speaker bios.
This season of DDx is sponsored by Sanofi.
Sanofi is a global healthcare company that develops and delivers medicines and vaccines for millions of people around the world.
Thanks for listening!