Can we not bleed?

Abstract

Few haematological conditions have captured the imagination in quite the same way as the bleeding disorder, haemophilia. Perhaps the connection of haemophilia with royalty has added an air of intrigue and mystique to the disease. Haemophilia has featured in a variety of popular culture throughout the ages from confounding the time of death in Dorothy L Sayers' mystery novel Have His Carcase to a cover for lycanthropy in Doctor Who to a young boy with the disease facing down Doctor Doom in Invincible Iron Man. While haemophilia might lend itself to stories, it is a very real disease that can be challenging to manage. Depending on the severity of the bleeding disorder, patients may have to undergo multiple infusions a week of recombinant clotting factors. These infusions take time, and patients risk developing inhibitors against the product used. However, research into recombinant clotting factors with longer half-lives is resulting in improvements in treatment schedules for patients. Efmoroctocog alfa is a recombinant factor VIII-Fc fusion protein and efrenonocog alfa is a recombinant factor IX-Fc fusion protein. These products have extended half-lives compared with conventional factor VIII and factor IX preparations, including recombinant products, and generally reduce prophylaxis infusions to once a week, or even once every 2 weeks, depending on the individual patient. Although there are no direct, head-to-head studies, the available clinical trial evidence indicates that these Fc fusion proteins provide an effective alternative to conventional preparations for the management of haemophilia A and B. Moreover, by reducing the frequency of injections required, these longer lasting clotting factors have the potential to reduce treatment burden, and hence improve adherence to prophylaxis. These two products have been approved for use by the US Food and Drug Administration since June, 2014, and by the European Medicines Agency since November, 2015. However, NHS England only confirmed reimbursement for the products on Sept 21, 2016, making them available across the UK. Cost is an issue which needs to be considered with such life long chronic treatments, and the financial burden can be significant if patients are not covered by insurance or health services. In the UK, the Prime Minister is considering setting up an independent panel to investigate historic use of contaminated blood, in which during the 1970s and 1980s about 5000 people in the UK were infected with hepatitis C and 1200 people with HIV during NHS treatment for haemophilia or blood transfusion. While victims in England have received discretionary payments from the government, no body or organisation has ever admitted liability or paid compensation over the affair. Although blood transfusion is no longer the standard of care in high-income countries, blood products are often still used in low-income countries, if available, and care must be taken to ensure that another such tragedy does not occur. It can be particularly difficult to treat paediatric patients with haemophilia. Frequent hospital visits and needle sticks for hundreds of infusions and other procedures can lead to anxiety about medical procedures, and long infusion times can result in children pulling at the infusion needles, by accident or boredom, leading to even longer procedures. A team at the Nationwide Children's Hospital in Columbus, OH, USA, has been developing a virtual reality game for paediatric patients to play during their infusions. The game, Voxel Bay, features an immersive world of penguins, pirates, and hermit crabs. The game runs off of a smart phone which sits in a lightweight cardboard headset—most importantly the game is controlled by head movements and breathing, leaving the hands and arms of the patient free for infusion, along with encouraging deep breaths which can help the children relax. The nurse can also see what the player sees in the game via a tablet and can therefore interact with the patient during the game and infusion. Although the project is in the early stages of development, the team hopes that it can be expanded to be used for patients receiving infusions at home to improve their experience. As treatment and therapy for haemophilia improves, the management of the disease can become an ever smaller part of a patient's life. New gene therapy trials are in progress, which may one day even lead to cure. Continued research into overcoming inhibitor development is a key challenge for patients in high-income countries, and for low and middle-income countries, work must be done to ensure patients are diagnosed properly and treated appropriately. Perhaps one day, haemophilia can be relegated to fiction, until then, we can work to ensure that people with bleeding disorders are as little affected by their condition as possible.