OVERVIEW

What is hemophilia?

Hemophilia is a blood disorder caused by genetic defects that result in a deficiency of clotting factors, leading to a prolonged state of easy bleeding. In healthy individuals, a series of clotting factors work together to seal damaged blood vessels when an injury occurs.

However, people with hemophilia cannot complete this clotting function, and even minor injuries can cause prolonged bleeding.

How common is hemophilia?

• The incidence of Hemophilia A is 1 in 5,000 male infants, with two-thirds being severe cases.
• The incidence of Hemophilia B is 1 in 30,000 male infants, with half being severe cases.

Due to genetic inheritance patterns, both Hemophilia A and B primarily affect males, especially severe cases, which are almost exclusively male.

• Hemophilia C affects both sexes equally. It is extremely rare in non-Jewish populations, with an incidence of approximately 1 in 1,000,000.

What are the types of hemophilia?

Hemophilia is classified into three types:

• Hemophilia A (also called Classic Hemophilia): The most common type, an X-linked recessive disorder caused by a deficiency of Factor VIII.
• Hemophilia B (also called Christmas Disease): Also X-linked, caused by a deficiency of Factor IX.
• Hemophilia C (also called Rosenthal Syndrome): An autosomal recessive disorder caused by a deficiency of Factor XI.

Patients with these three types are further classified as mild, moderate, or severe based on the level of clotting factor deficiency. Mild hemophilia has 5%–40% of normal clotting factor levels, moderate hemophilia has 1%–5%, and severe hemophilia has less than 1%.

Is hemophilia hereditary?

Hemophilia is a genetic disorder.

A key feature is that Hemophilia A and B are X-linked, meaning the defective gene is on the X chromosome, leading to different manifestations in males and females. The disease primarily affects males.

If a child is born with hemophilia to unaffected parents, the child will always be male, and the mother is the carrier of the defective gene. Since males have only one X chromosome, inheriting the defective gene will always result in the disease, not a carrier state.

Females, having two X chromosomes, can still maintain over 50% clotting factor activity when carrying one defective gene, so they typically show no symptoms. Rare symptomatic females usually have only mild hemophilia. For female carriers, the main concern is that any male child has a 50% chance of inheriting hemophilia.

Hemophilia C is an autosomal disorder, affecting males and females equally with no gender bias.

SYMPTOMS

What are the main manifestations of hemophilia?

The primary manifestation of hemophilia is bleeding, especially after trauma, surgery, or minor injuries, where bleeding often does not stop. However, in many cases, bleeding may occur spontaneously without any apparent cause, such as gum oozing or joint swelling.

Patients with mild hemophilia may experience symptoms later in life, sometimes even delayed until adulthood. The severity and frequency of bleeding depend on the patient's clotting factor levels.

If these symptoms occur, it is important to seek medical attention from a hematology department rather than just visiting a specialist for the bleeding site.

What are the characteristics of hemophilia-related bleeding?

• Platelet counts are normal, but bleeding cannot be stopped.
• The condition is congenital and lifelong, though umbilical cord bleeding at birth is extremely rare.
• Weight-bearing joints like the knees and ankles often bleed repeatedly, potentially leading to joint deformities.
• Muscle bleeding is common, mainly presenting as hematomas at the bleeding site.

Do hemophilia patients always experience bleeding?

Whether hemophilia causes clinical symptoms or bleeding depends mainly on the level of normal clotting factors.

• When clotting factor activity is 5%–40% of normal (mild hemophilia), spontaneous bleeding does not occur, but abnormal bleeding may happen during surgery or trauma.
• When clotting factor activity is 1%–5% of normal (moderate hemophilia), occasional spontaneous bleeding may occur, and severe bleeding can happen during surgery or trauma.
• When clotting factor activity is less than 1% of normal (severe hemophilia), typical spontaneous muscle or joint bleeding may occur.
• For clotting factor activity at 25%–45% (subclinical hemophilia), the condition may only be discovered after severe trauma or major surgery due to prolonged bleeding, making it easily missed. Some female carriers of the hemophilia gene may also exhibit bleeding symptoms similar to mild male hemophilia patients due to comparable clotting factor levels.

What other diseases can hemophilia cause?

Complications of hemophilia mainly result from long-term chronic bleeding. For example, joint bleeding can lead to deformities, retroperitoneal bleeding may cause paralytic ileus, anemia, or shock, lower abdominal bleeding can block the ureter and lead to kidney dysfunction or failure, bleeding near nerves may cause nerve damage, and neck bleeding can compress the airway, leading to suffocation.

The most common sites of hemophilia-related bleeding are the skin and muscles, followed by joint cavities. Internal organ bleeding is rare but severe, while intracranial bleeding can be life-threatening.

CAUSES

What substance is the deficient clotting factor in hemophilia?

Clotting factors are substances that promote blood coagulation during the clotting process. Only with the presence of clotting factors can platelets adhere together and ultimately achieve hemostasis.

What is X-linked recessive inheritance in hemophilia?

The sex chromosome karyotype of males is XY, while that of females is XX. X-linked recessive inheritance means the disease-causing gene is located on the X chromosome and is only transmitted through the X chromosome.

Therefore, when a male carries this disease-causing gene, he will definitely develop the disease. However, when a female carries only one copy of this gene, she will not develop the disease and is merely a "carrier." She will only develop the disease if both X chromosomes carry the disease-causing gene.

Will the children of a hemophiliac male and a healthy female have hemophilia?

Based on the chromosome karyotype mentioned earlier, their sons will not inherit hemophilia and will be healthy. Their daughters will 100% be carriers of the hemophilia gene (carrying the gene without developing symptoms) but will not exhibit clinical manifestations of hemophilia.

Will the children of a female carrier of the hemophilia gene and a healthy male have hemophilia?

Their sons have a 50% chance of having hemophilia. If they have a daughter, she will 100% not develop the disease, but there is a 50% chance she will be a carrier of the hemophilia gene.

Will the children of a hemophiliac male and a female carrier of the hemophilia gene have hemophilia?

In this case, if the child is a boy, there is a 50% chance of having hemophilia. If the child is a girl, there is a 50% chance of either developing the disease or being a carrier. Regardless of gender, there is also a 50% chance of being completely normal.

Will the children of a hemophiliac male and a hemophiliac female have hemophilia?

In this scenario, regardless of gender, the children will 100% have hemophilia.

If both parents are healthy, does that mean their children will definitely not have hemophilia?

Not necessarily. Hemophilia is primarily inherited from parents, but gene mutations in the child can also cause the disease.

In such cases, even if both parents are healthy, the child may still develop hemophilia due to a gene mutation, and this hemophilia gene can be passed on to the next generation.

DIAGNOSIS

Which department should hemophilia patients visit?

Hematology Department, Pediatric Hematology Department.

What tests should be done to diagnose hemophilia?

Suspected hemophilia mainly requires the following laboratory tests:

• Coagulation function test: Mainly measures activated partial thromboplastin time (APTT), which is significantly prolonged in hemophilia patients;
• Coagulation factor activity test: Directly measures the activity of coagulation factors 8, 9, or 11; vWF:Ag and ristocetin cofactor activity tests (normal in hemophilia patients) should also be performed to differentiate from von Willebrand disease;
• Genetic diagnosis: Directly detects abnormal hemophilia genes.
  (Note: The terms factors 8, 9, and 11 are used for reader understanding; the standard medical terms are factors VIII, IX, and XI.)

What is the difference between hemophilia and leukemia?

There are significant differences between the two, mainly in the following aspects:

• Different causes

  • Hemophilia: A congenital recessive genetic disorder caused by genes on the X chromosome, so patients are almost exclusively male. Deficiency of coagulation factors Ⅷ and Ⅸ leads to hemophilia A and B, respectively.
  • Leukemia: An acquired disease, a malignant tumor of the blood system. The onset may be partially related to genetics but is mainly influenced by various factors such as living environment, exposure to radiation, or harmful substances. Children of cured leukemia patients do not inherit the disease.

• Different clinical manifestations

  • Hemophilia: Only related to coagulation, with the most notable clinical symptoms being spontaneous bleeding or excessive bleeding after minor trauma. Common manifestations include gum and skin bleeding, hematuria, joint bleeding, and hematomas; symptoms often appear from childhood, with bleeding severity proportional to disease severity.
  • Leukemia: Common symptoms include fever, anemia, bleeding, hepatosplenomegaly, and bone pain, often with acute onset. Blood tests show thrombocytopenia, while coagulation factor levels are usually normal.

• Different treatments

  • Hemophilia: The cause is clear, and the most effective measure is replacement therapy to supplement the missing coagulation factors.
  • Leukemia: As a malignant tumor, the main treatment is chemotherapy, along with other options like differentiation induction, targeted drugs, and bone marrow transplantation.

• Different prognoses

  • Hemophilia: Early detection, diagnosis, and replacement therapy, along with avoiding activities that may cause bleeding, do not affect long-term survival.
  • Leukemia: Like other malignant tumors, it severely threatens life. For example, untreated acute leukemia has a natural course of only 3–6 months, and even with aggressive treatment, the five-year survival rate is less than 50%.

What are the methods for early detection of hemophilia?

The main current method is prenatal genetic testing.

• Prenatal diagnosis of hemophilia can be performed at 8–10 weeks of pregnancy via chorionic villus sampling to determine fetal sex and detect pathogenic genes;
• Amniocentesis for genetic diagnosis can be done at 15 weeks of pregnancy;
• At 18–20 weeks of pregnancy, fetoscopy can be used to obtain umbilical vein blood for chromosomal analysis, gene polymorphism analysis, and fetal coagulation factor activity level testing.

TREATMENT

How is hemophilia treated?

Treatment measures for hemophilia include the following aspects:

• Replacement therapy (supplementing what is deficient): Since hemophilia is caused by abnormal clotting factors leading to bleeding, the primary treatment currently involves supplementing the deficient clotting factors. This can be done by directly infusing artificially gene-recombinant clotting factors or administering fresh frozen plasma or cryoprecipitate containing clotting factors.
• Medication: For superficial abrasions, cuts, or nosebleeds, topical hemostatic agents such as thrombin, gelatin sponge, or epinephrine can be used for compression. Replacement therapy is usually unnecessary, but desmopressin, danazol, or hormones may be applied if needed.
• Surgical treatment: Mainly addresses joint deformities and dysfunction caused by long-term recurrent joint bleeding.
• Prevention: Since hemophilia cannot be cured, preventive measures are crucial, such as avoiding bumps, injuries, and strenuous exercise.

What are the basic principles of hemophilia treatment?

• Strengthen self-protection to prevent traumatic bleeding and avoid intramuscular injections.
• Address bleeding as early as possible.
• Avoid taking aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or medications that interfere with platelet aggregation, such as dipyridamole.
• Schedule regular follow-ups.

How can hemophilia patients manage home treatment?

Home treatment refers to patients or their family members self-administering clotting factor replacement products at home or work. As hemophilia is a chronic, lifelong condition, home treatment is extremely important. It generally includes emergency first aid for critical situations and preventive therapy.

Emergency first aid involves immediate self-injection for bleeding in critical areas, followed by seeking professional help. Preventive therapy refers to self-injection before anticipated bleeding or strenuous activity.

Note that home treatment should not be performed under the following circumstances:

• Unstable condition.
• Children under 3 years old.
• Patients with inhibitory antibodies.

What should be noted during replacement therapy for hemophilia?

Since replacement therapy mainly involves infusing deficient clotting factors (mostly blood products), potential risks include transfusion-related viral infections, immune suppression, and allergic reactions.

What are the adverse effects of replacement therapy for hemophilia?

Possible adverse effects include:

• Transfusion-related viral infections (e.g., hepatitis, HIV).
• Immune suppression (e.g., inhibited lymphocyte proliferation and cytokine production, reduced resistance).
• Allergic reactions (e.g., fever, rash).

What is the current status of recombinant clotting factors in hemophilia treatment?

Recombinant clotting factors are the most effective treatment for hemophilia. Available products include recombinant factor VIII, factor IX, and activated factor VII, all of which are commercially available through specialized channels.

Can hemophilia patients undergo surgery?

Yes, depending on the condition.

For surgery, sufficient blood supply and clotting factor preparations must be secured. Major surgeries (e.g., heart, lung, or brain) require clotting factor levels of 50%–80% one hour pre-operation and maintenance at 30%–50% for 7–10 days post-operation. If complications like infection occur, clotting factor infusion should be prolonged.

Can hemophilia be cured?

Currently, there is no cure for hemophilia. It is a lifelong condition requiring ongoing treatment.

How should life-threatening bleeding in hemophilia patients be managed?

The most effective method is prompt, adequate clotting factor replacement therapy to rapidly elevate levels to 50%–80% for 1–2 weeks.

What is the RICE principle for acute joint or muscle injuries in hemophilia patients?

RICE stands for Rest, Ice, Compression, Elevation:

• Rest: Stop activity immediately to prevent further injury.
• Ice: Apply ice to reduce inflammation, pain, and swelling (15–20 minutes per session, with breaks). Use a towel for children to avoid frostbite.
• Compression: Bandage the injured area to minimize swelling.
• Elevation: Raise the injured limb to reduce bleeding and swelling.

DIET & LIFESTYLE

Can children with hemophilia get vaccinated?

Yes, individuals with hemophilia can and should receive vaccinations. Children with hemophilia should get the hepatitis B vaccine as early as possible. When vaccinating, avoid intramuscular injections—opt for intradermal injections instead, using the smallest needle possible. After injection, apply pressure and ice. Oral polio vaccines (sugar pills) should not be used; inactivated polio vaccines are recommended instead.

What precautions should hemophilia patients take in daily life?

• Dental care:

  • Begin dental cleanings in infancy, practice proper brushing techniques, and use fluoride toothpaste. Fluoride varnish can be considered for baby teeth. Maintaining oral hygiene helps prevent cavities and gum diseases, as traumatic dental procedures should be minimized for hemophilia patients.

• Avoid injuries, collisions, and unnecessary needle sticks:

  • Seek immediate medical attention for head injuries, even if asymptomatic, to receive clotting factor replacement. Spontaneous intracranial bleeding is a severe complication. For joint bleeds, absolute rest and immobilization are necessary. Inform all healthcare providers about the hemophilia diagnosis. Avoid medications like aspirin, ibuprofen, and naproxen. Use acetaminophen for fever relief. For children with hemophilia, ensure all caregivers, teachers, and school staff are aware of the condition and prepared for emergency injury management.

• Prevent obesity and excess weight:

  • Engage in low-impact or static activities while avoiding high-impact sports. Reduced physical activity leading to obesity can also harm health. Seek professional guidance for optimal exercise routines.

• Dietary considerations:

  • Avoid hard, spiky, or extremely hot foods. Keep sharp objects away from young children. Maintain a balanced and varied diet for proper nutrition.

Can hemophilia patients have healthy children?

Male hemophilia patients do not pass the defective gene on their Y chromosome, so their sons will not inherit the disease, but their daughters will always be carriers. Female carriers have a 50% chance of passing the gene to their daughters (who become carriers) and a 50% chance of having sons with hemophilia.

PREVENTION

Can Hemophilia Be Prevented?

Since it is caused by genetic defects, prevention mainly involves prenatal genetic counseling, where parents and doctors jointly select an appropriate pregnancy plan.

If there is a history of hemophilia in the family, it is advisable to conduct genetic testing before conception to determine whether the parents carry the hemophilia gene.

If the gene is indeed present, fetal gender can be assessed during pregnancy, as male fetuses of female carriers have a 50% chance of inheriting the disease. In such cases, invasive procedures on the fetus should be avoided to prevent bleeding complications.

After birth, interventions such as forceps delivery or vacuum extraction should also be avoided. If fetal malposition or difficult vaginal delivery occurs, an elective cesarean section may be considered.