Living with Hemophilia: Expert Insights on Management and Treatment

Hemophilia is a rare, inherited blood disorder that causes one’s blood to clot less, which results in an increased risk of bleeding or bruising. Hemophilia happens because one’s body doesn’t make enough protein (clotting factors) to help blood form clots. Clotting factors are proteins in one’s blood. They work with platelets to form blood clots that control bleeding. Low clotting factor levels increase bleeding risk. There are several types of Hemophilia. Hemophilia may be severe, moderate or mild based on the amount of clotting factor in your blood. Conventionally, the healthcare providers managed this condition by replacing the missing clotting factor (Replacement therapy/Prophylaxis). However, now with the non-factor prophylactic treatment made available, this provides superior and durable bleed protection than conventional therapies.

There are three types of hemophilia:

• Hemophilia A: This is the most common type of hemophilia. It happens when you don’t have enough clotting factor 8 (factor VIII). The CDC estimates about 10 in 100,000 people have hemophilia A.

• Hemophilia B: Hemophilia B happens when you don’t have enough clotting factor 9 (factor IX.) The CDC estimates about 3 in 100,000 people in the U.S. have hemophilia B.

• Hemophilia C: Hemophilia C is also known as factor 11 (factor XI) deficiency. This hemophilia type is very rare, affecting 1 in 100,000 people.

The most significant symptom is unusual or excessive bleeding or bruising. People with hemophilia may develop large bruises after minor injuries. This is a sign of bleeding under their skin. They may bleed for an unusually long time, whether that’s bleeding after surgery, bleeding after dental treatment or simply bleeding from a cut finger. They may start bleeding for no apparent reason, such as sudden bloody noses. How much bruising or bleeding people have depends on whether they have severe, moderate or mild hemophilia: People with severe hemophilia often have spontaneous bleeding or bleeding for no apparent reason. People with moderate hemophilia who have serious injuries may bleed for an unusually long time. People with mild hemophilia may have unusual bleeding, but only after major surgery or injury. Other symptoms may include:

• Joint pain from internal bleeding: Joints in your ankles, knees, hips, and shoulders may ache, swell, or feel hot to the touch.

• Bleeding in the brain; People with severe hemophilia very rarely develop life-threatening bleeding in their brains. Brain bleeds may cause persistent headaches, double vision or make you feel very sleepy.

There are two main modes of replacement therapy for hemophilia patients: either to stop bleeding (on-demand) or regular infusions of clotting factor to prevent bleeds (prophylaxis). Current treatment options include:

• Plasma-derived clotting factors

• Recombinant Factor Concentrates

• Extended Half-life Factor Products

• Non-factor therapy: Emicizumab (only approved drug in India)

Unlike other replacement therapies which require infusion via IV route up to 2-3 weeks, non-factor therapies offer a convenient subcutaneous form of treatment with a maintenance dosing frequency of once a month.

All forms of prophylaxis (with Clotting Factor Concentrates or prophylaxis with non-factor replacement agents,e.g. emicizumab) provide superior benefits over episodic/On demand therapy. Conventional prophylaxis, initiated early in life, has been associated with over 90% reduction in joint bleeding rates, annualized joint bleeding rates (AJBRs) below 3 per year, and a significant reduction in joint deterioration and degenerative joint disease.

• Prophylaxis also provides protection from other types of hemorrhages in hemophilia, including preventing or substantially reducing the risk of intracranial hemorrhage.

• Longer-term benefits include reduction of chronic musculoskeletal pain, functional limitations, and disability, need for orthopedic surgery, hospitalization, emergency room visits, and reduced length of hospital stays; all of this leads to greater participation (i.e., regular attendance) in educational, recreational, and professional activities, with improved quality of life.

• Because of these benefits, the World Health Organization (WHO), the World Federation of Hemophilia (WFH), and many national and international hemophilia organizations have endorsed early prophylaxis as the standard of care for children with a severe phenotype hemophilia and recommend that prophylaxis be continued lifelong.

Additionally, adults with severe phenotype hemophilia (if not already on prophylaxis) should initiate prophylaxis as well.

• Lack of awareness of disease among healthcare workers and patients.

• Lack of diagnostic facilities

• Lack of continuous supply of clotting factor concentrates

• Lack of uniform protocols for the management of hemophilia across the country

• Due to lack of access there will be a delay in the diagnosis of new cases

• Existing cases of hemophilia if they suffer any new bleed they have to travel long distances to receive factor concentrate. This is very important especially when they get life-threatening bleeds like an intracranial bleed

• Delay in diagnosis of hemophilia patients with inhibitors

We had 17-year-old twins who were suffering from hemophilia A. I saw them for the first time in March of 2021 march. At that time their mother used to bring both of them from a distance of 80km to Hyderabad. Most of the time they are not used to walking due to bleeding in the psoas muscle or bleeding in knee joints and used to have a lot of pain. They were depressed and not used to attending college regularly. It's not only the patients, the entire family used to suffer.

We have screened them for inhibitors and one of them was positive for inhibitors. We have started one child on factor 8 prophylaxis and another on emicizumab prophylaxis.

Both of them are not having any spontaneous bleeding. Now they are attending college regularly. They come to take factors without their parents' help now. They are doing regular physiotherapy and have a better quality of life.

Challenges with existing treatments are they have to be given intravenous route, more frequent administration, and risk of inhibitor development.

Newer therapies like extended half-life factors can be given less frequently

Drugs like Emicizumab can be given subcutaneous route, once a month and do not affect inhibitor formation

More exciting therapies like gene therapy which offer cures are still under clinical trials

Due to recurrent spontaneous bleeds many patients if not treated properly develop target joints and joint deformities. This will eventually lead to disability which causes school or work absenteeism and lead to depression and poor quality of life

Early diagnosis and treatment of hemophilia is important because it can:

• Prevent tissue damage: Treating bleeding with factor replacement therapy as soon as possible can stop bleeding before tissue is damaged.

• Reduce the need for factor concentrates: Early treatment can reduce the amount of factor concentrates needed and help patients recover more quickly.

• Prevent hemophilic arthropathy: Early treatment with clotting factor concentrates can prevent hemophilic arthropathy.

• Improve long-term prognosis: Early detection, follow-up, and treatment can improve patients’ long-term prognosis.

• Reduce mortality: Prompt diagnosis and treatment can reduce mortality.

• Prevent neurological sequelae: Prompt diagnosis and treatment can prevent neurological sequelae.

Physical therapy is essential for reducing disability and improving the quality of life. Individualized rehabilitation programs could have a positive impact on the management of pain, joint health, and disability improvement. Joint mobilization and muscle stretching techniques have been reported as effective methods for improving joint health, range of motion, and joint pain.

The goal of the treatment of a child with hemophilia is to enable the patient and their families to manage the illness as independently as possible and therefore lead more normal, healthy lives. It is important to provide primary prophylaxis to children to avoid target joints and subsequent disabilities.

For adults with hemophilia, it is important to reduce bleeding and severity of bleeding episodes. This can help prevent permanent joint damage and even death. Improving quality of life and life expectancy for people with hemophilia.

Despite different goals of therapy, the treatment modalities are common across age groups.