What Causes Hemophilia?

Posted on August 13, 2018

The vast majority of hemophilia and other bleeding disorders are congenital – present at birth – and due to a defective gene. Even in milder cases where symptoms do not become apparent until later in childhood or even adulthood, most bleeding disorders are caused by a faulty gene that controls the production of a clotting factor. People with the defective gene may make too little of the key factor, or the factor may not work properly.

Among congenital disorders, most are inherited – passed down in a clear pattern in families. Less often, the genetic defect is a random mutation that happens only in the person affected and does not involve a family history of bleeding disorders or inheritance. Even more rarely, a bleeding disorder is not congenital and not genetic, but acquired later in life. If the cause of an acquired bleeding disorder is known at all, it is usually caused by another health condition or a medication.

Causes of bleeding disorders

Blood clots by a complex process called the coagulation cascade. The coagulation cascade involves many different proteins called factors. Each factor plays a vital role in blood clotting. If any one of these factors is deficient or ineffective, blood cannot clot correctly, and dangerous bleeds may result. In hemophilia and related bleeding disorders, the body either makes too little of a clotting factor or makes an abnormal, ineffective version of the factor.

Inherited genes

Hemophilia A and hemophilia B are well-known as inherited bleeding disorders. The genes for hemophilia A and hemophilia B are passed down on the X chromosome in a recessive pattern. Each person inherits an X chromosome from their mother and either an X or a Y chromosome from their father. Males have XY chromosomes, while females have XX chromosomes. If a boy receives an X with the gene for hemophilia, he develops hemophilia. If a girl receives one X chromosome with the hemophilia gene, her normal X chromosome usually cancels out the defective gene – she is unlikely to have any symptoms of hemophilia, and if she does, they will probably be mild. However, she will be a carrier for the hemophilia gene and may pass it on to her children.

Spontaneous mutations

About one-third of people with hemophilia have a defective gene for a clotting factor but no family history of bleeding disorders. In cases like these, the gene is believed to be the result of a sporadic mutation in that individual.

Acquired bleeding disorders

In rare cases, people are not born with hemophilia but develop it later in life as a result of another health condition or a medication. In acquired hemophilia, something triggers the immune system to misidentify a clotting factor as an invasive foreign substance and begin attacking and destroying it. The immune attack lowers the level of the misidentified clotting factor, resulting in a bleeding disorder. Acquired hemophilia can be caused by cancer, liver disease, vitamin K deficiency, rheumatoid arthritis, lupus, Sjögren’s syndrome, pregnancy, or infections. More than half of acquired hemophilia is unknown in cause, or idiopathic. Acquired hemophilia, which can be very severe, affects between 1 and 1.5 people per 1 million. Unlike most other types of bleeding disorders, acquired hemophilia can sometimes go away if the underlying problem – health condition or medication – is resolved.

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