Overview

Published: LifeLines for Health, vol. 3 (Summer 2014)

Today, nearly 40 years after effective treatments for hemophilia A became widely available, there are many of us living with an inhibitor that causes uncontrolled bleeding episodes, increased disability and decreased quality of life. For some of us, these effects can be compared to those individuals who lived with hemophilia prior to factor replacement. In approximately 30% of all individuals with severe hemophilia A, inhibitors form in response to FVIII therapy, rendering any routine treatment ineffective.

Due to the history of pathogen transmission in the 70’s and mid 80’s from human-source FVIII, recombinant

FVIII is often the only treatment option patients are given. As many of us have discovered, however, not all FVIII products work the same for each of us. Some of us have found that after years of unsuccessfully trying to treat with different recombinant products, bleeding episodes can be managed better with human-source FVIII.

Due to the changes and advances in plasma collection, manufacturing and production over the past 20 years, perhaps it is reasonable to consider human- source FVIII as an option for patients with difficult to treat symptoms of hemophilia A.

History of Factor VIII

Human-source FVIII became widely available in the 1970’s, allowing hemophilia A patients, for the first time, to treat bleeding episodes at home, to travel and to have surgery1. These products created a significant improvement in the quality of life for individuals with hemophilia. Lengthy hospital stays and lengthy treatments became a thing of the past. The lifespan of an individual with hemophilia A could now be increased dramatically. It wasn’t long after their introduction however, that it was discovered the use of human-source FVIII carried a risk of pathogen transmission. Many of us had family members who became infected in the 1970’s and 1980’s. It was by far the most tragic era in the history of hemophilia treatment.

Recombinant versions of FVIII, first introduced in the early 1990’s,1 were not just hailed as welcome additions to the hemophilia A treatment toolbox, but signified a complete change in the way we treat hemophilia A to this day. Along with increased product choice and supply of available treatments, the risk of pathogen transmission was significantly decreased. Prophylaxis treatment became the standard of care, drastically reducing the number and severity of bleeds and the subsequent joint damage they cause. For many of us, prophylaxis meant the ability to live an otherwise “normal” life with the opportunities to participate in sports and other activities that would have been considered too risky, dangerous or impossible.

Inhibitor Development Necessitates a New Outlook

Managing a chronic neutralizing inhibitor is a daunting challenge. Its’ impact on the individual and the family’s overall quality of life is debilitating.Many of us have spent precious years and resources attempting immune tolerance induction (ITI) with large, frequent infusions of recombinant FVIII,or large, frequent volumes of bypassing agents with little to no success. The options for treatment are extremely limited, while the bleeds andcomplications are abundant. Reconsidering human-source FVIII – not an easy choice given our community’s history, as a way to manage bleeding episodes soon became the only choice for many of us. Faced with a diminished quality of life, many of us consulted with our medical teams or began researching the safety of human- source plasma on our own as a possible treatment option. What was found was that our bleeding episodes could again be managed. For many, immune tolerance was successfully completed with human-source product.

It is highly doubtful that there is a single medication, prescription or otherwise that does not carry the risk of side effects, some more harmful than others. As stewards of our own (or our child’s) health, it is imperative to know the risks, consequences and benefits of any medication we use. Our community should never forget the devastating effects of products that were not stringently screened, tested and manufactured.

The biggest challenge in the hemophilia community today is inhibitors. Although no one can say with certainty what causes them, we do know that at least 30% of the severe hemophilia A population will develop one. We as custodians of our own (or child’s) health in conjunction with our health care team need to know all of the options for treatment available to us, along with their possible consequences. This knowledge for those of us living with an inhibitor could make a drastic difference in bleed management, joint health and overall quality of life.

Final Thought

We do not all have the same response to FVIII products. There are those of us who develop inhibitors or are poor half-life responders. We have learned that some of us do respond successfully to human-source FVIII products.

No one knows for sure why, but after years of uncontrolled bleeding, many of us wish we had considered human-source products long ago. We would like to encourage physicians, nurses, and caregivers that it is okay to bring up the topic of human-source FVIII products in the discussion with patients and parents, and vice-versa.

Authored by:

Jake Rollins - Adult with severe hemophilia A. Human-source FVIII successfully tolerized his inhibitor.

Janet Brewer - Mother of 2 sons with severe hemophilia A. One of her sons developed an inhibitor which was partially tolerized after switching to human-source FVIII.

Eric Lowe - Adult with severe hemophilia A. Human-source FVIII successfully tolerized his inhibitor.

References

1. Lusher JM. Development and introduction of recombinant factor VIII - a children’s experience. Haemophilia. 2012;18:483-86

2. Viel KR, Afshin A, Abshire TC, lyer, RV et.al. Inhibitors of Factor VIII in black patients with hemophilia. N Engl J Med. 2009;360:1618-27.

3. www.pptaglobal.org Plasma Protein Therapeutics Association (PPTA)

4. Klamroth R et al. Pathogen inactivation and remocal methods for plasma-derived clotting factor concentrates. Transfusion. 2013:9.