Last Updated: June 06, 2018

Hemophilia

Overview

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:

DNA health testing allows us to check for genetic risk of Hemophilia C.

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 inheritance

Hemophilia 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:

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:

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

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Authored by: Tina Shahian, PhD