Haemophilia. A word recognised by most people but understood by few: “the one that means you bleed a lot”. But for people with haemophilia (PwH), it is anything but that simple.
For people with haemophilia, the diagnosis is life-changing. They must administer complex medication regimes and manage symptoms of chronic and acute pain. They can’t play contact sports, such as rugby, due to the increased risk of bleeding and must ensure they are medicating appropriately, as even common pain medications further exacerbate their symptoms. Going to the dentist or needing simple surgeries becomes a complex task, with entire teams of haemophilia specialists being required to manage the associated bleeds. Nearly half of all young adults with haemophilia report anxiety or depression, while a third report that their haemophilia has affected their ability to develop close relationships.1 This cohort also reported that haemophilia had a negative impact on their employment, with these factors undoubtedly impacting negatively on patients’ quality of life.
Haemophilia is caused by a genetic mutation on one of two genes found on the X chromosome: F8 or F9. Depending which gene carries the mutation, you will either have haemophilia A (F8) or haemophilia B (F9), and the type of mutation (and how this affects the levels of the gene product) will dictate how severe your disease is. These genes encode clotting factors, factor VIII (FVIII) and factor IX (FIX) respectively, which form part of an activating cascade to coagulate blood and form clots in response to damage; a process known as haemostasis. Without sufficient levels of either one of these factors, your ability to clot blood is affected, and this can lead to an array of problems, ranging from sudden nosebleeds and internal bleeding into joints to, in severe cases, brain haemorrhage.2
But is there anything we can do to help? Strategies for treating haemophilia have undeniably improved in recent decades. Where previous plasma-derived clotting factor concentrates commonly resulted in transmission of blood-borne pathogens such as HIV and Hepatitis C, development of recombinant clotting factors avoid this issue.3 Where haemophilia was associated with a decreased life expectancy, PwH can now expect to match the life expectancy of the general population. Patients now have the choice between on-demand and preventative (also known as prophylactic) treatments and can self-administer infusions at home. Comprehensive care centres for treating haemophilia are now widely available and there is a large amount of disease education available to patients.
However, there are still problems. Of patients who take blood clotting factor concentrates, ~30% of people with haemophilia A and ~10% of people with haemophilia B will produce antibodies against these, called inhibitors.4 These will bind to and destroy the clotting factor concentrates being added and therefore is a huge issue. Inhibitors can be treated with immune tolerance induction (ITI), where frequent injections of clotting factors over months, or sometimes years, will force the immune system to recognise them as safe. Bypass therapy and immunosuppressants can also aid in overcoming inhibitors, but are associated with another complement of risks and side effects, as well as increased cost. In low-resource settings progress is slow, and globally most PwH do not have access to appropriate treatment.5
But there is still hope. New therapies are continually in development and hold promise for PwH. Clotting factor concentrates are being developed that have longer half-lives, reducing the patient burden for medicating.6 Recent gene therapy trials have provided promising results for long-term treatment of haemophilia, with adeno-associated virus (AAV)-based vectors eradicating both the incidence of bleeding episodes and the need for clotting factor replacement therapy in some cases.7–9 While further research is needed to fully understand the biology of AAV vector delivery, these approaches provide promise.
This Sunday, 17th April, marks World Haemophilia Day 2022. It is important to reflect on the problems still faced daily by PwH and remember those that are tirelessly acting to improve diagnosis, outcome and treatment access for all.