Haemophilia treatment breakthroughs: Pros, cons and future directions

Haemophilia is a hereditary disorder that affects the ability of the body to form blood clots because of deficiency of factor VIII or IX but people with haemophilia can have active, meaningful lives provided they receive a regimen of factor replacement along with a well-organised exercise regimen to strengthen the muscle groups around major joints. With the development of medicine and technology, along with cooperative efforts between patient groups, physicians and the government for improved access to factors, management of this bleeding problem has improved in the last few decades.
In an interview with HT lifestyle, Dr Kannan Subramanian, Consultant Hematologist at Sahyadri Speciality Hospital in Pune’s Deccan Gymkhana, highlighted the primary risks connected to hemophilia treatment –
This is one of the most challenging complications in hemophilia treatment. Around 25 to 30% patients develop inhibitors against the clotting factors used in their treatment, particularly those with hemophilia A. These inhibitors can make the standard treatments less effective, necessitating alternative strategies and sometimes more intensive treatments.
While much safer today due to rigorous screening and the use of synthetic products, there remains but a small risk of viral transmission with plasma-derived treatments. It’s a reminder of the importance of ongoing vigilance in product safety.
Frequent bleeding into joints, a common issue for those with severe hemophilia, can lead to long-term joint damage and pain. This is why preventing bleeds with regular treatment is so crucial, though sometimes damage accumulates subtly over time.
Some patients might experience allergic reactions to their clotting factor treatments, which can range from mild to severe. This risk is particularly noted with certain factor IX products used in hemophilia B.
As treatments improve and patients live longer, other health risks like cardiovascular disease become more prominent. It’s important for treatment plans to consider overall health, including heart health, especially since traditional risk factors like reduced activity from joint problems can contribute.
New treatments, such as gene therapy, offer potential long-term solutions but come with their own set of uncertainties and risks, like potential immune reactions or long-term effects that are still being studied.
Regular infusions can be demanding and affect quality of life, especially for those without access to the latest extended half-life treatments. Managing these can be a logistical and emotional challenge for many.
Dr Kannan Subramanian shared, “Managing haemophilia effectively requires a thoughtful, patient-centered approach that balances these risks with the benefits of treatment, aiming to provide the best possible quality of life. It’s a collaborative effort between patients, families and healthcare providers to navigate these complexities together.”
Bringing his expertise to the same, Dr Santanu Sen, Consultant – Paediatrics, Paediatric Hematology, Oncology and Stem Cell Transplantation at Kokilaben Dhirubhai Ambani Hospital in Mumbai, said, “Haemophilia, a genetic disorder that impairs clotting, poses significant risks and challenges for those affected by the disease. While advancements in medical treatments have vastly improved the quality of life for haemophiliacs, the treatment of the disease is not without risks.”
He revealed, “The main defect in haemophilia is the absence of clotting factors which makes the sufferers have life-threatening bleeding, at times with even trivial injuries. Dental procedures such as teeth extraction can lead to non-stop bleeding and surgical procedures without replacement of clotting factors can lead to severe bleeding and even death. Minor falls can lead to bleeding in joints which can lead to lifelong disability due to joint destruction.”
According to Dr Santanu Sen, the main treatment for haemophilia remains clotting replacement therapy, whereby these factor concentrates are directly injected into the bloodstream. He said, “However, even this essential treatment carries a risk of developing inhibitors, which are antibodies that attack the infused clotting factors. Inhibitors can occur in up to 30% of patients with severe haemophilia. They can significantly complicate the management of the disorder, leading to more frequent bleeding episodes and reduced efficacy of treatments. Patients with high levels of inhibitors can become resistant to therapy and treatment can become tough.”
Another major concern is the risk of infections. Dr Santanu Sen said, “In the past, a significant proportion of haemophilia patients had been accidentally infected with HIV, Hepatitis C and Hepatitis B through the use of contaminated clotting factors. Though modern blood screening techniques have greatly reduced the transmission of these infectious diseases, there remains some risk, particularly if stringent screening protocols are not followed. This highlights the importance of rigorous standards and consistent monitoring needed to ensure the safety of blood products used in treatment. In a country like ours, the cost of haemophilia treatment is often a significant burden to patients. Though blood-derived clotting factors are available at a nominal cost to patients in government hospitals, modern and safer replacement therapies are quite expensive, leading to severe financial burdens or even putting them beyond the reach of many patients. For many patients in our country, the disparity in income levels means that these modern therapies remain an unmet need forever.”
Dr Santanu Sen pointed out, “Gene therapy, the most promising development in haemophilia treatment, aims to provide a long-term solution by introducing correct versions of defective genes to the patient. This possibly is the best and only cure for the disease. It remains prohibitively expensive and possibly would remain beyond the paying capacity of the majority of patients in our country for many years to come but even this state-of-the-art therapy is not without risks. Gene therapy carries unknown long-term risks including abnormal immune responses to the therapy itself or unforeseen genetic complications. The uncertainty surrounding these outcomes necessitates continued and ongoing research. While advances in treatments offer hope to haemophilia patients, the associated risks must be carefully managed. Continuous research, improved safety measures, and equitable access to modern treatment are crucial to ensure the best possible outcome for all patients.”
Dr Farah Jijina, Consultant – Clinical Hematology at PD Hinduja Hospital and MRC in Khar, concluded, “Patients of haemophilia who are treated with factor concentrates also can develop problems. One of the major problems which occurs is, the development of inhibitors due to which treatment with the factor becomes ineffective. The treatment of haemophilia inhibitors is extremely expensive, and many of our patients are not able to afford it. Besides this, patients can have what we call breakthrough bleeds and they can continue to have further joint damage and develop progressive joint disease. In children, prophylactic factor regimes, lead to problems of IV access and infections.”