The monarchies of of Europe may have been some of the most powerful families in the world, but little did they know that a genetic mutation would wreak havoc in their royal blue bloodlines. Starting from what is now thought to be a spontaneous mutation in one of Queen Victoria’s X chromosomes, haemophilia cast its deadly net far and wide, spreading into the royal families of Russia, Spain, and parts of Europe. Not only did it cause multiple ‘mysterious deaths’ after minor falls and stumbles, but it also left its deadly imprint on the historical trajectories of many of these empires.
Haemophilia, further classified into subtypes A, B, and C, is a group of genetic disorders in which a genetic mutation leads to under-expression of the clotting factors essential for fibrin clot formation. According to a global survey conducted by the World Federation for Hemophilia, India has the second-highest load of patients with hemophilia A in the world, and is the only developing country amongst the top five countries.
Understanding the mechanism of blood clotting
A fibrin clot weaves through the platelet plug, forming a stable clot that stops bleeding following an injury. In the absence of these clotting factors, the coagulation cascade —that involves a set of 13 factors—remains incomplete, leaving the platelet plug friable and prone to rupture, causing re-bleeding.
While a skin scratch bleeds more than expected, it is the profuse bleeding in joints, muscles, soft tissues, and visceral organs that raise an alarm. An injury on the chest wall can cause hemoperitoneum, while a fall on the head can become as severe as a haemorrhagic stroke. Joint bleeds remain common, causing a patient excruciating pain and difficulty in walking. Chronic bleeding can eventually lead to the development of deformities and contractures.
While prenatal testing is available in developed countries, in developing countries any episode of unwarranted bleeding usually causes suspicion of the disease. Excessive bleeding during normal physiological processes like menstruation or surgical procedures such as circumcision and tooth extraction might cause a doctor to suspect a clotting disorder. In fact, the Talmud, the Jewish religious text from 200 B.C.E., prohibits circumcision for the third son if two other sons have died of excessive bleeding. But the problem with such incidental diagnosis is that the only bleeding episode might be life-threatening. I remember a patient, unaware of his diagnosis, being wheeled into my emergency room with a pulmonary haemorrhage. Dissecting the lung was the only option left with us at that time.
Underdiagnosis, a problem
Underdiagnosis due to inadequate screening and coagulation facilities, and lack of awareness remain a serious problem in India. To understand this gross underdiagnosis, one can compare the prevalence rates, which are 8-11 times lower in India when compared to other developed countries. Almost 80% of patients remain undiagnosed in India.
We have come a long way in the treatment of hemophilia from the time when excruciatingly tight bandages were used to keep children still. Queen Victoria refers to her eighth son, Prince Leopold, who suffered from haemophilia, as a ‘prisoner in his own nursery’ who was ‘banned from any active amusement while the other children had a run of Osborne House.’ CFC (clotting factor concentrates) has been a wonder treatment that has given patients with haemophilia a new lease of life. However, advanced technology and high costs make availability of factors difficult for all patients. As per a WFH survey, while 43% of the world’s haemophilia population lives in India, Bangladesh, Indonesia, and China, only 2% of the world’s total factor is being utilised. The per capita use of clotting factor VIII concentrate in India was 0.271 IU in 2020, significantly lower than the average limit of 1 IU decided by WFH.
In remote areas, whole blood is still used whenever available. Most poor patients have to content themselves with popping painkillers, supportive therapy such as the RICE (Rest, Ice, Compression, Elevation) regimen, and, if lucky, a shot of tranexamic acid. Usage of factors comes with a host of problems. Transfusion-related infections have been on the rise, with almost 20% of Indian haemophiliacs infected with the Hepatitis C virus (HCV) and other malignancies. Moreover, the presence of inhibitors, antibodies against the clotting factors, causes the haemostatic properties of the factors to go for a toss. Substantial morbidity and mortality are recorded, while the cost of treatment exponentially increases.
Lack of prophylaxis regimens
One of the central problems in India with regard to haemophilia remains the lack of prophylaxis regimens. The factor replacement happens after an episode of bleeding has already happened. While this episodic use might reduce pain and prevent debilitating disability, it doesn’t significantly alter the bleeding profile or change the natural history of the disease.
In India, prophylaxis adoption is estimated at around 4 %. In contrast, in most other developing countries, it is over 20 %, and in developed countries, 80-90 % of patients are on prevention, states Naresh Gupta, chairperson of HHCN (Hemophilia and Health Collective of North), in a report released last year.
The physical, emotional, and psychological toll on PwH (Persons with Hemophilia) is immense. Patients with hemophilia have to tread in public spaces with extreme caution. It causes school dropouts, frequent absenteeism, scholastic backwardness, lower social competencies, downward social mobility in careers, and mental health issues.
A March 2024 research study in the journal Heliyon estimates the per-patient cost of treating a hemophiliac in India to be $300,000 (or ₹2.54 crore) over a 10-year period. This cost is likely to be increased by comorbidities such as arthropathy, debilitating pain, temporary or permanent disability, transfusion-related infections, and other age-related disorders. Moreover, with patients requiring frequent visits to healthcare facilities and prolonged periods of rest, abstinence from work for the patient as well as the caregiver can ramp up indirect costs.
The inclusion of PwH within the ambit of the Rights of Persons with Disabilities (RPWD) Act, 2016, is a welcome step that might help in mainstreaming the rights of persons with haemophilia, but its translation into ground-level improvement remains abysmal. Studies have shown that the transition from on-demand factor replacement to prophylactic would not pose a substantial economic burden while also promising a far better clinical profile for the patient.
On the other hand, there have been reports of healthcare workers indulging in the ethically wrong practice of injecting small quantities of factors. Drug stockouts remain a serious problem and need to be smoothed out. Last year, a budget cut caused patients from Maharashtra to move to Gujarat to get treatment.
Advances in treatment and the path forward
The treatment armamentarium for haemophilia should expand to include diverse options. Last year, a novel gene therapy developed by scientists at Christian Medical College, Vellore and tested on five patients showed promise. Prophylaxis drugs such as Hemlibra (Emicizumab) have outstanding results in patients with inhibitor hemophilia. Public-private partnerships, NGOs, and CSR (corporate social responsibility) funds might be explored to operationalise such highly advanced and expensive treatment protocols.
Enhancing the skills of frontline workers and establishing diagnostic and treatment facilities at the district level are crucial steps toward improving care.
Integrating prenatal diagnostic tests into routine antenatal check-ups can aid in early detection. Most Haemophilia Day Care Centres (HDCCs) only replenish the factor without taking a holistic, multidisciplinary approach. HDCCs should expand, to bring together physiotherapy, pain management, and rehabilitative services under one roof.
Research also suggests that home-based treatment can significantly lower both disability rates and healthcare costs, as public infrastructure is not conducive to the needs of such patients.
A large section of India’s haemophilia population continues to suffer without recognition. The time has come to break this silence and respond with urgency and empathy.
(Kinshuk Gupta is a public health researcher and author of Yeh Dil Hai Ki Chordarwaja. [email protected])
Published – April 17, 2025 12:00 pm IST