Hemophilia

Overview

By Tina Shahian, PhD

The blood clotting process is critical for preventing excessive blood loss when the body is injured. Hemophilia is a genetic disorder where protein factors that help blood clot are missing, or not fully functional. As a result, those with hemophilia experience prolonged bleeding following injury, surgery or even minor trauma. Severe forms of the disease may cause spontaneous bleeding in the absence of any trauma to the body. Bleeding internally into the joints, brain or other organs can lead to serious complications when left untreated.

There are three main types of hemophilia (A, B and C) depending on which clotting factor is affected:

  • Hemophilia A: deficiency in clotting factor VIII
  • Hemophilia B: deficiency in clotting factor IX
  • Hemophilia C: deficiency in clotting factor XI.

These clotting proteins act in concert as part of an extensive coagulation pathway that plugs the damaged site by activating platelets and fibrin proteins. Clotting efficiency is determined by the amount of functional clotting factors available. Hemophilia A and B are the most common disease types and have a higher incidence in males. Worldwide, roughly 1 out of 5,000 males have hemophilia A, while 1 out of 20,000 males have hemophilia B, at birth. The risk of developing hemophilia is the same across different ethnicities.

Causes and Risk Factors

US government diagram explaining x-linked recessive inheritanceHemophilia is an inherited disorder, which means the underlying genetic abnormalities are passed down from parents to their offspring. Hemophilia is the result of mutations (errors) in the genes that encode clotting factors VIII, IX and XI. These mutations lead to less effective versions of the clotting proteins, or their complete absence. When the critical concentration of clotting factors is not present in the body, clots form slower and bleeding is hard to control.

The mutations that are linked to hemophilia are on the X chromosome. Females receive two copies of the X chromosome (one from each parent), so gene products from one normal X chromosome often make up for any deficiencies present on the second X chromosome. Since inheriting two defective copies of the same gene is rare, the majority of females are carriers; they carry one hemophilia gene and can clot blood normally.

Males have a much higher chance of developing hemophilia because they only receive one copy of the X chromosome (from their mother). Instead of a second X chromosome, they inherit a Y chromosome (from their father), which does not duplicate the gene content of the X chromosome. Therefore, one defective X chromosome is sufficient for developing hemophilia. Hemophilia is called an X-linked trait because only mothers can pass it down to their sons.

A rare form of hemophilia known as “acquired hemophilia” is not due to inheritance, but instead happens when the body launches an immune attack against clotting factor VIII. This form of hemophilia begins in adulthood and leads to spontaneous internal bleeding into the joints, muscles and other tissue. Acquired hemophilia is not fully understood, but is linked to cancer, immune disease, allergies and pregnancy.

Hemophilia Symptoms

All symptom of hemophilia are related to uncontrolled or unexpected bleeding, either externally (e.g. skin cut, nosebleed) or internally (e.g. knee, muscle, brain). The extent of bleeding depends on the amount of functional clotting factors present in the body; when the amount of clotting factor is low, bleeding symptoms become more severe. Internal bleeding into the joints, muscle and brain is serious and requires immediate medical attention. The following bleeding symptoms are associated with hemophilia:

  • Excessive bleeding following minor injuries (e.g. skin cut)
  • Large skin bruises from bleeding within the skin
  • Uncontrolled bleeding after receiving a shot or pulling a tooth
  • Frequent nosebleeds that are hard to stop
  • Blood in the urine or stool
  • Pain and swelling in the joints due to internal bleeding
  • Infantile bleeding after birth or circumcision
  • Headaches and difficulties with vision.

Diagnosis and Treatment

Hemophilia is diagnosed using blood tests that assess clotting efficiency and measure for specific clotting proteins. People with hemophilia or with a family history of hemophilia can inquire about testing for themselves or their children. Prenatal tests for hemophilia are available, but they pose some risk to the fetus. Hemophilia is usually diagnosed between the age of 9 months and 2 years. Sometimes the disorder remains undetected until excessive bleeding following a surgery or injury.

There is no cure for hemophilia so treatment is achieved by replacing the missing clotting factors that allow blood to clot. The clotting proteins are generated recombinantly in the laboratory, purified from human blood or provided as part of whole plasma, and administered by infusion. With proper care, most people with hemophilia can live normal lives. The treatment choices include:

  • Infusions: Injections with the hormone desmopressin (DDAVP) helps stimulate the body to produce more clotting factor. This therapy is used to stop bleeding in patients with mild hemophilia A. One-time or repeated infusions of human-derived clotting factors or whole donated blood are used to stop bleeding in hemophilia A and B patients with moderate to severe disease. In the United States, hemophilia C patients are treated with plasma infusions. Routine at-home DDAVP and clotting factor infusions may be required.
  • Other medications: Topically applied fibrin sealants promote clotting and are helpful during dental procedures. Antifibrinolytic drugs help preserve a clot once it is formed.
  • First aid: Applied pressure, bandage and ice are helpful ways to prevent excessive blood loss from minor topical injuries.
  • At home: Hemophilia patients should avoid blood-thinning or other medications that slow the blood clotting process. Wearing protective equipment will help avoid injuries to the body.

Prevention

Hemophilia is an inherited disorder that cannot be prevented. Those with a family history of the disease can ask their doctors about diagnostic testing for themselves and their children.

Sources

  • “Hemophilia". National Hemophilia Foundation. Retrieved May 28, 2015. https://www.hemophilia.org/.
  • “Hemophilia". Mayo Clinic Foundation. Retrieved May 28, 2015. http://www.mayoclinic.org/diseases-conditions/hemophilia/basics/definition/con-20029824.
  • “Hemophilia”. Centers for Disease Control and Prevention (CDC). Retrieved May 28, 2015. http://www.cdc.gov/ncbddd/hemophilia/facts.html.