Hemophilia A

Description of the Disease

Hemophilia A is an inherited bleeding disorder (coagulopathy) caused by a deficiency of clotting factor VIII, which is essential for normal blood coagulation. Along with hemophilia B and C, it is one of the most common inherited bleeding disorders, accounting for approximately 70–80% of all hemophilia cases. The disorder is inherited in an X-linked recessive pattern. The factor VIII gene, one of the largest genes in the human genome, is located on the long arm of the X chromosome. In approximately half of affected males, mutations such as intrachromosomal recombination, deletions, point mutations, or inversion of intron 22 are identified. The type of mutation influences the severity of the disease. Intron 22 inversion is associated with a more severe form, whereas missense mutations are generally associated with a milder course.

Hemophilia A primarily affects males, while females are usually asymptomatic carriers. An affected male passes the mutated gene to all of his daughters, making them carriers, but none of his sons inherit the disorder. A female carrier has a 50% chance of having a son with hemophilia and a 50% chance of having a daughter who is also a carrier.

Symptoms

All forms of hemophilia are characterized by bleeding into the skin, joints, muscles, gums, nose, gastrointestinal tract, and genitourinary tract. Severe bleeding following trauma, major wounds, or intracranial hemorrhage may be life-threatening and requires immediate medical attention.

The severity of bleeding depends on the level of factor VIII activity in the blood. When factor VIII activity is less than 1%, the disease is classified as severe, and spontaneous bleeding is common. When factor VIII activity exceeds 5%, the disease is considered mild and typically presents with prolonged bleeding after minor injuries or surgical procedures.

In newborns, hemophilia may be suspected if cephalohematomas develop or if prolonged bleeding occurs from the umbilical stump or after intramuscular injections. Excessive bleeding during teething is uncommon, but bleeding caused by injuries to the oral mucosa is relatively frequent.

Symptoms often become more apparent when children begin walking, as falls and minor trauma may result in extensive bruising, particularly around the head, eyes, buttocks, and genital area. The knees, ankles, and elbows are the joints most commonly affected.

Joint involvement may present as:

• Acute hemarthrosis: Sudden severe joint pain accompanied by swelling, redness, warmth, and tense skin over the joint. Pain usually subsides rapidly after appropriate factor replacement therapy or joint aspiration when indicated.
• Chronic hemophilic arthropathy: Recurrent bleeding into the joints gradually damages the cartilage, causes synovial membrane thickening and fibrosis, and eventually leads to bone destruction.
• Secondary rheumatoid syndrome: Symmetrical inflammatory arthritis affecting joints that have not previously bled. These joints become painful, deformed, and are often associated with morning stiffness.

Diagnosis

Hemophilia A should be suspected in any boy with spontaneous or unexplained bleeding. Diagnosis includes a complete blood count, platelet count, coagulation studies, bleeding time, clotting time, thrombin and prothrombin tests, and measurement of factor VIII activity. In families with a history of hemophilia, female relatives may undergo DNA analysis and genetic testing to identify carrier status. Prenatal diagnosis can be performed by chorionic villus sampling at 10–12 weeks of pregnancy or by amniocentesis after 15 weeks of gestation.

Treatment

The main treatment for hemophilia A is replacement therapy with factor VIII concentrates. Preventive (prophylactic) treatment includes plasma-derived or recombinant factor VIII concentrates produced using genetic engineering. The dose is administered intravenously every 8–24 hours, depending on the severity of bleeding and clinical circumstances. During joint bleeding, the affected joint should be immobilized for 2–3 days or supported with a compression bandage. Ice packs may be applied for 3–5 minutes at a time, and the affected limb should be kept elevated during the first few days. In some cases, blood must be aspirated from the joint, followed by intra-articular hydrocortisone administration and intravenous factor VIII replacement therapy.

Source | Author Doctor Nikas Samuolis, reviewed by Prof. Virginijus Šapoka | Vilnius University | Faculty of Medicine | Head of the Department of Internal Medicine, Family Medicine, and Oncology