Hemophilia

What is hemophilia?

From: MedlinePlus, National Library of Medicine

Hemophilia is a rare bleeding disorder in which the blood does not clot properly. This can lead to problems with bleeding too much after an injury or surgery. You can also have sudden bleeding inside your body, such as in your joints, muscles, and organs.

Your blood contains many proteins called clotting factors that can help form clots to stop bleeding. People with hemophilia have low levels of one of these factors, usually either factor VIII (8) or factor IX (9). How severe the hemophilia is depends on the amount of factor in the blood. The lower the amount of the factor, the more likely it is that bleeding could happen and might lead to serious health problems.

What are the types of hemophilia?

From: MedlinePlus, National Library of Medicine

There are several different types of hemophilia. The most common are:

• Hemophilia A (classic hemophilia), which is caused by a lack or decrease of clotting factor VIII (8)
• Hemophilia B (Christmas disease), which is caused by a lack or decrease of clotting factor IX (9)

What causes hemophilia?

From: MedlinePlus, National Library of Medicine

Most types of hemophilia are inherited. They are caused by change in one of the genes (also called a mutation) that provides instructions for making the clotting factor proteins. The change may mean that the clotting proteins don't work properly or that they are missing altogether.

These genes are on the X chromosome. You may have one or two X chromosomes:

• People who are born male have one X chromosome (from the mother) and one Y chromosome (from the father). They can get hemophilia if their one X chromosome has the gene change.
• People who are born female have two X chromosomes, one from the father and one from the mother. They usually only get hemophilia if: Both X chromosomes have the gene change OR One X chromosome has the gene change and the other X chromosome is missing or inactive. People who are born female who have the gene change on one X chromosome are a "carrier" of hemophilia. Sometimes they may have some symptoms of hemophilia. They can pass the gene change on to their children.

Hemophilia that is not inherited is called acquired hemophilia. It is rare. It happens when your body makes specialized proteins called autoantibodies that attack and disable a clotting factor. This can happen because of pregnancy, immune system disorders, cancer, or allergic reactions to certain medicines. Sometimes the cause is unknown.

Who is at risk for hemophilia?

From: MedlinePlus, National Library of Medicine

Hemophilia is much more common in people who were born male since they can get it with a change to the gene on one X chromosome. People who have a family history of hemophilia are also at higher risk.

What are the symptoms of hemophilia?

From: MedlinePlus, National Library of Medicine

The signs and symptoms of hemophilia are:

• Bleeding into the joints. This can cause swelling and pain or tightness in the joints. It often affects the knees, elbows, and ankles.
• Bleeding into the skin (which is bruising).
• Bleeding into the muscle and soft tissue, which can cause a build-up of blood in the area (called a hematoma).
• Bleeding of the mouth and gums, including bleeding that is hard to stop after you lose a tooth.
• Bleeding after circumcision.
• Bleeding after having shots, such as vaccinations.
• Bleeding in the head of an infant after a difficult delivery.
• Blood in the urine or stool.
• Frequent and hard-to-stop nosebleeds.

In some cases, severe hemophilia may cause bleeding in the brain. This may cause brain damage and can be life-threatening.

How is hemophilia diagnosed?

From: MedlinePlus, National Library of Medicine

To find out if you have hemophilia, your health care provider will:

There is genetic testing for the factor VIII (8) and factor IX (9) genes. This testing may be used in people who have a family history of hemophilia to:

• Ask about your medical history, including your symptoms and other health conditions you may have.
• Ask about your family history, to find out if you have relatives who have or had hemophilia.
• Do a physical exam to look for signs of hemophilia, such as bruising.
• Do certain blood tests to show if your blood is clotting properly. If it does not, then you will have clotting factor tests to diagnose the cause of the bleeding disorder. These blood tests would show the type of hemophilia and the severity.
• Identify people who are carriers before they make decisions about pregnancy
• Test a fetus for hemophilia during pregnancy
• Test a newborn for hemophilia

What are the treatments for hemophilia?

From: MedlinePlus, National Library of Medicine

The best way to treat hemophilia is to replace the missing clotting factor so that your blood can clot properly. This is usually done by injecting replacement clotting factor into a vein. The replacement clotting factor may be made from donated human blood. Or it may be made in a lab; this kind is called a recombinant clotting factor.

Replacement clotting factor can help treat a bleeding episode. In more severe cases of hemophilia, you might get the factor on a regular basis to prevent bleeding. You can learn how to inject the factor so that you can do it yourself at home.

There are other medicines to treat hemophilia. They may work by releasing factor VIII (8) from where it is stored in the body tissues, replacing the function of factor VIII (8), or preventing clots from breaking down.

If bleeding has damaged your joints, physical therapy may help them function better.

Good quality medical care from healthcare professionals who know a lot about the disorder can help prevent some serious problems. Often the best choice for care is to visit a hemophilia treatment center (HTC).

Genetic causes described in the linked summary

From: MedlinePlus Genetics

Variants in the F8 gene cause hemophilia A, while variants in the F9 gene cause hemophilia B. The F8 gene provides instructions for making a protein called coagulation factor VIII. A related protein, coagulation factor IX, is produced from the F9 gene. Coagulation factors are proteins that work together in the blood clotting process. After an injury, blood clots protect the body by sealing off damaged blood vessels and preventing excessive blood loss.

Variants in the F8 or F9 gene lead to the production of an abnormal version of coagulation factor VIII or coagulation factor IX, or reduce the amount of one of these proteins. The altered or missing protein cannot participate effectively in the blood clotting process. As a result, blood clots cannot form properly in response to injury. These problems with blood clotting lead to continuous bleeding that can be difficult to control. The variants that cause severe hemophilia almost completely eliminate the activity of coagulation factor VIII or coagulation factor IX. The variants involved in mild and moderate hemophilia reduce but do not eliminate the activity of one of these proteins.

Another form of the disorder, known as acquired hemophilia, is not caused by inherited gene variants. This rare condition is characterized by abnormal bleeding into the skin, muscles, or other soft tissues, usually beginning in adulthood. Acquired hemophilia results when the body makes specialized proteins called autoantibodies that attack and disable coagulation factor VIII. The production of autoantibodies is sometimes associated with pregnancy, immune system disorders, cancer, or allergic reactions to certain drugs. In about half of cases, the cause of acquired hemophilia is unknown.

Inheritance described in the linked summary

From: MedlinePlus Genetics

Hemophilia A and hemophilia B are inherited in an X-linked recessive pattern. The genes associated with these conditions are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In females (who have two X chromosomes), a variant would usually have to occur in both copies of the gene to cause the disorder. However, in some instances, one altered copy of the F8 or F9 gene is sufficient, because the X chromosome with the normal copy of the gene is turned off through a process called X-inactivation. X-inactivation occurs early in embryonic development in females. Through this process, one of the two X chromosomes is permanently turned off (inactivated) in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell.

Usually X-inactivation occurs randomly, such that each X chromosome is active in about half of the body cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation.

In many females with a variant in one copy of the F8 or F9 gene, X-inactivation is random and the chromosome with the normal copy of the gene is turned off in about half of cells. These individuals have about half the usual amount of coagulation factor VIII or coagulation factor IX, which is generally enough for normal clotting. However, in some females with an F8 or F9 gene variant, X-inactivation is skewed, and the chromosome with the normal copy of the gene is turned off in more than half of cells. These individuals can have less coagulation factor VIII or coagulation factor IX than usual and are at risk of abnormal bleeding.

Which doctor should you see?

The suggested department for discussing Hemophilia is Haematology, with a haematologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which blood-cell, marrow, bleeding or clotting finding matters most?
• Does the diagnosis need confirmation or a more precise subtype?
• Which symptoms or laboratory changes should trigger earlier review?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.