Hemophilia

What is Hemophilia

Hemophilia is a bleeding disorder where sufferers tend to bleed for a longer time than non-sufferers. In simple words, Hemophilia is a condition in which the patient does not have a specific protein called ‘clotting factors’ or ‘Coagulation Factor Concentrates’ (CFC). This keeps their blood from clotting normally in the event of cuts.

The deficiency or absence of clotting factors happens due to a genetic change or mutation. This mutation prevents instructions about the formation of clotting factor proteins from being provided. As a result, the patient lacks the necessary amount of clotting factors in the blood, leading to uncontrolled bleeding in the patient.

There are two common types of Hemophilia. The more commonly found form is called Hemophilia A, caused by a deficiency in factor VIII or AHF. Hemophilia B is a much rarer form, caused by a factor IX deficiency. This form of Hemophilia was only discovered in 1952, and is also called the ‘Christmas disease’ after the surname of the first child with its diagnosis.
Hemophilia is not a killing disease and does not by itself impact the patient’s lifespan. It is not a curable condition; however, with proper physician-directed treatment and management, an active and fulfilling life is entirely possible for the PwH.

History

The history of Hemophilia goes back to ancient Egyptian texts which record people experiencing irregular bleeds, a symptom of bleeding disorders including Hemophilia. Mentions of the condition have been found in Jewish texts from the second century AD, and in the writings of an Arab physician in the 11th-12th century.

Hemophilia was first described in the modern world by a Philadelphian physician named Dr. John Conrad Otto. The word ‘Hemophilia’ was first used to describe a bleeding disorder at the University of Zurich by a student named Friedrich Hopff.

The Royal Disease

Hemophilia has the dubious honor of being called the ‘royal disease’. This is because of its impact on several European royal families in the 19th and 20th centuries. Queen Victoria of England was a carrier of the disease. It is believed that she came to be a carrier of the condition through a spontaneous genetic mutation. She passed it on to two of her daughters and her son Leopold. Tragically, Leopold became a premature victim of the condition when he passed away at the age of 31 after suffering a fall. Queen Victoria’s daughters Alice and Beatrice, also carriers, passed it to their children. The condition spread to the royal families of Russia, Spain and Germany through marriages. The eldest son of Tsar Nicholas II of Russia, Tsarevich Alexis, has the most scandalous story associated with Hemophilia in history. It has been speculated that his condition led to severe strain within the royal family, facilitating the rise of Rasputin’s influence and the eventual downfall of the dynasty.

Symptoms and Diagnosis

Hemophilia often remains undiagnosed until the occurrence of medical mishaps such as a fall that leads to excessive bleeding, or during surgery. Some symptoms to look out for may include:

• Unusual and excessive bruising
• Frequent and hard-to-stop nosebleeds
• Bleeding after vaccinations or other injection shots
• Bleeding after tooth-loss, or bleeding of the gums and mouth
• Joint pain from internal bleeding into joints or muscles

Signs to look out for in females:

• Heavy and painful menstrual bleeds and mid-period pain
• Bleeding during vaginal sex or intercourse
• Bleeding during gynecological conditions
• Excessive bleeds during regular gynecological procedures and childbirth

Signs suggestive of Hemophilia in babies and toddlers are:

• Bleeding after minor injuries such as bumping into toys
• Swollen lumps on heads
• Hematomas – a mass of congealed blood under the skin, often after receiving an injection shot

Hemophilia is usually inherited. It is considered a rare disorder, with 1 in every 5000 males being born with it. Hemophilia cannot be transmitted – people cannot catch Hemophilia from one another, unlike infectious diseases like the flu.

India has over 1.4 lakh cases of patients living with Hemophilia, making it home to the second largest population of PwH in the world.

Diagnosis is done through application of screening coagulation tests and includes:

• Screening tests to ascertain appropriate clotting of blood
• Clotting factor tests (or factor assays)

Genetic Inheritance

Hemophilia is usually an inherited disease. It is passed down from parents to children over generations through their genes. The genes that control the production of factors VIII and IX are located on the X chromosome; therefore Hemophilia is called an X-linked disorder.
Males have XY chromosomes while females have XX chromosomes . The chances of children inheriting the condition from parents can be observed in the following chart

• All female children will inherit the affected X chromosome from the father and become carriers of Hemophilia.
• No male children will be affected since they will inherit only the Y chromosome from the father and the X chromosome from their mother.

For a non-affected father and a mother with one affected gene:

• For each child of both male and female gender, there will be a 50% chance of inheriting the affected X chromosome from the mother. In the case of a son inheriting the affected chromosome, he will have Hemophilia. In the case of a daughter inheriting the affected chromosome, she will become a carrier for the Hemophilia gene.

For a father with Hemophilia and a mother with a carrier gene for Hemophilia:

• All male children will have a 50% chance of having Hemophilia by inheriting the affected gene from the mother.
• For all female children the daughter will either be a carrier of the Hemophilia gene or or be a Hemophilia patient herself.
• It is uncommon for children to have both parents with altered X chromosomes, and so women rarely inherit this disease.

Occasionally Hemophilia can occur from spontaneous mutations in a person’s own genes. In these cases there is no known family history of the condition.

Genetic Counseling

Genetic counseling assists individuals in fully understanding and adapting to the medical, psychological, and familial impacts of genetic factors in diseases.

There are several key elements to genetic counseling:

• Assessing family and medical histories to determine likelihood of disease
• Educating the family about inheritance of diseases
• Testing for various genetic conditions
• Recommending resources for management of genetic conditions
• Guidance for lifestyle adaptation to various diseases
• Enabling informed decision-making for during family planning

The objective of genetic counseling is to empower patients to make well-informed health decisions using genetic insights. Genetic counseling encompasses information sharing and evaluating its impact on patients and families. It holds significance for both inherited and sporadic genetic conditions, profoundly influencing individuals and families.
Genetic counselors are specialized healthcare practitioners with the skills to engage in conversations about risk evaluation, genetic testing, disease control, and prevention. They play key roles as advocates, communicators, and educators, effectively explaining the pros and cons of various options available to families and caregivers of patients, as well as couples in the process of family planning.
In conditions like hemophilia, genetic counseling aids understanding and adjusting to the diagnosis, especially for reproductive decisions. It offers insights into reproductive choices, both natural and assisted, facilitating family planning preparation. Genetic counseling is crucial in addressing the potential of having a child with hemophilia. In conjunction with genetic test results, genetic counselors provide an enhanced evaluation of risks and the array of choices that confront those affected by hemophilia.

Women and Girls with Hemophilia

For a long time it was assumed that females could only be carriers of Hemophilia and not patients themselves. However recent advances in medical understanding have dispelled this as a myth.

As many as one-third of all women with the altered genes display symptoms of Hemophilia. This usually happens when a female individual has inherited two affected X chromosomes from a Hemophiliac father and a carrier or Hemophiliac mother. While this is a rare occurrence, the possibility of female Hemophilia patients cannot be negated altogether.

Many women often spend a significant portion of their lives with symptoms of Hemophilia without suspecting a bleeding disorder being suspected or diagnosed.

Apart from the regular symptoms of Hemophilia, the most obvious symptom for females is unusually heavy and prolonged bleeding during menstruation.

Some other symptoms to look out for are:

• Pain in the middle of menstrual cycle. This pain occurs secondary to bleeding from the ovary at the time of egg release into
  the peritoneal cavity (the space within the abdomen that contains the abdominal and pelvic organs) which irritates the peritoneum
  (the membrane that connects and supports the internal organs in the pelvis and abdomen).
• Vaginal bleeding during sex, unscheduled bleeding while taking hormonal therapy, and postmenopausal bleeding.
• Bleeding and/or pain with common gynecological conditions, such as uterine fibroids and endometriosis.
• Excessive or prolonged bleeding following a gynecological procedure or surgery.

Treatment and Management

While there is no known cure for Hemophilia, there are effective methods of management.
For mild to moderate bleeds, the patient’s factor levels can be supplemented through CFC.
In the absence of CFC, Fresh frozen plasma (FFP) and Cryoprecipitate are used. FFP has 2X times CFC as fresh blood; Cryoprecipitate has 2X time CFC as FFP.
Advancement of prophylactic treatments in recent years has improved the prognosis for PwH. Treatment through bispecific antibodies and factor mimetic agents injected under the skin once a week to once a month, depending on the severity of the condition, can significantly reduce pain and disability in PwH.
Regular check-ups are vital for Hemophilia management. Physiotherapy also plays a very important role in pain management and mobility for PwH.
In India, on demand therapy of injecting factors post-bleed is frequently used. However, the risks of joint and muscular damage are fairly high for this method.
A particularly effective physiotherapy protocol named POLICE can be used in the case of bleeds. This stands for Protection, Rest, Optimal Loading, Ice, Compression and Elevation – and this protocol can be used at home.

Prohibitive costs and inadequate resources

Unfortunately, treatment for Hemophilia remains beyond reach for the vast majority of Indian patients. Human blood products like pure CFC tend to be extremely expensive at almost Rs 12 per unit. In India, a single CFC injection can cost up to Rs 10,000, and with individual bleeds sometimes needing 2 or 3 injections, the treatment becomes unattainable.
Additionally, many hospitals and medical colleges lack screening facilities for clotting factors. This impacts the diagnosis of new cases. There is significant lack of awareness about the disease amongst primary care physicians and even specialists, leading to frequent misdiagnosis.