Hemophilia

How hemophilia affects clotting

Clotting depends on a chain of proteins called clotting factors. Factors VIII and IX are essential links in that chain. Without enough of either, the body forms a weak clot slowly, so bleeding continues longer. People with hemophilia do not bleed faster, but they bleed for longer and can re-bleed.

Severity

Types of hemophilia

• Hemophilia A: factor VIII deficiency; about 80 to 85% of cases.
• Hemophilia B: factor IX deficiency, also called Christmas disease after the first patient described.
• Acquired hemophilia: a rare, non-inherited condition in which the immune system makes antibodies against factor VIII, usually in older adults or after childbirth.

Von Willebrand disease is a different, more common inherited bleeding disorder that affects males and females equally.

Inheritance

The genes for factors VIII and IX are on the X chromosome.

• A father with hemophilia passes the gene to all his daughters (who become carriers) and none of his sons.
• A carrier mother has a 50% chance with each son of passing on hemophilia and a 50% chance with each daughter of passing on carrier status.
• About one third of cases occur in families with no previous history, from a new gene change.

Many carriers have lower-than-normal factor levels, and some have mild hemophilia, with heavy periods and bleeding after childbirth or surgery. Carrier testing is recommended for female relatives.

Symptoms

• easy bruising, with large, raised bruises
• joint bleeds (hemarthrosis): knees, elbows and ankles most often; early tingling or warmth, then pain, swelling and stiffness
• muscle bleeds: painful swelling in the calf, thigh, forearm or groin
• prolonged bleeding from cuts, tooth loss, dental work or surgery
• bleeding after circumcision, or after vaccinations or heel-prick tests in babies
• nosebleeds and bleeding gums
• blood in urine or stool
• intracranial bleeding: the most dangerous; can follow minor head injuries

Diagnosis

• Family history often prompts testing at or before birth.
• Clotting tests: a prolonged activated partial thromboplastin time (aPTT) with a normal prothrombin time (PT) and platelet count.
• Factor VIII and IX levels confirm the type and severity.
• Genetic testing identifies the specific gene change, helping with carrier testing and family planning.
• Inhibitor testing: checks for antibodies against infused factor.

Prenatal testing and newborn cord blood testing are available for families with known hemophilia.

Treatment

Care is best coordinated through a hemophilia treatment center, where hematologists, nurses, physical therapists and others work together.

Preventive treatment (prophylaxis)

Regular treatment to keep clotting ability high enough to prevent bleeds is standard for severe hemophilia:

• Factor replacement: intravenous factor VIII or IX concentrate, given at home several times a week, or less often with extended half-life products. Families and patients learn to self-infuse.
• Emicizumab: a weekly to monthly injection under the skin for hemophilia A that mimics factor VIII activity, with or without inhibitors.
• Other non-factor therapies: newer medicines that rebalance clotting, given by injection under the skin.
• Gene therapy: one-time treatments approved for some adults with hemophilia A or B, which allow the liver to make the missing factor.

Treating bleeds

• Give factor or other prescribed treatment early, ideally at the first sign of a joint bleed.
• Rest, ice, compression and elevation for joint and muscle bleeds.
• Desmopressin can raise factor VIII levels in mild hemophilia A.
• Antifibrinolytics (tranexamic acid) help with mouth and nose bleeds and dental procedures.

Inhibitors

About 1 in 4 to 1 in 3 people with severe hemophilia A develop antibodies (inhibitors) that neutralize infused factor. Options include bypassing agents, emicizumab and immune tolerance induction.

Everyday precautions

• Avoid aspirin and NSAIDs such as ibuprofen, which impair platelets. Acetaminophen (paracetamol) is usually safe for pain.
• Get vaccines under the skin rather than into muscle when possible, or with pressure afterward.
• Regular dental care to prevent gum bleeding and extractions.
• Stay active with low-contact sports such as swimming and cycling; physical therapy protects joints.
• Wear medical ID.

Complications

• Hemophilic arthropathy: repeated joint bleeds damage cartilage, causing chronic pain and stiffness.
• Intracranial bleeding.
• Inhibitor development.
• Infections from older blood products: many people treated before the late 1980s acquired HIV or hepatitis C; modern products are virus-inactivated or recombinant.

Outlook

With modern prophylaxis, life expectancy for people with hemophilia in countries with good access to care is close to normal, and most children grow up without significant joint damage. Access to treatment remains the major determinant of outcome worldwide.

Frequently asked questions

What is the difference between hemophilia A and B?

Hemophilia A is caused by a lack of clotting factor VIII, and hemophilia B by a lack of factor IX. Their symptoms are the same. Hemophilia A is about 4 times more common. They are treated with different factor products, and some newer treatments work only for one type.

Can women have hemophilia?

Yes. Women who carry the gene can have low factor levels and mild hemophilia, with heavy periods and bleeding after childbirth, surgery or dental work. Rarely, women have moderate or severe hemophilia. Female relatives of people with hemophilia should be tested.

What are the first signs of hemophilia in a baby?

Signs include prolonged bleeding after circumcision, large bruises when starting to crawl or walk, swelling after vaccinations, and bleeding from the mouth after minor injuries. Babies with a family history are usually tested at birth.

Can hemophilia be cured?

There is no routine cure, but gene therapies approved for some adults can raise factor levels for years, greatly reducing or eliminating bleeds. For most people, preventive treatment with factor or non-factor therapies controls bleeding effectively.