Factor XIII deficiency - F13A1 and F13B genes

Factor XIII deficiency, also known as fibrin stabilizing factor deficiency or Laki-Lorand factor deficiency, is a rare blood clotting disorder. Has been identified a hereditary form, and another form that is acquired during the life of a person and that manifests itself with less intensity.

The signs and symptoms of this process begin shortly after birth, usually with abnormal bleeding from the umbilical cord. If the disease is not treated, affected individuals may have episodes of excessive and prolonged bleeding that can be potentially fatal after minor surgery or trauma. Factor XIII deficiency can also lead to spontaneous bleeding in the joints or muscles, which causes pain and disability. Affected women tend to manifest menorrhagia and may have spontaneous abortions. Other signs and symptoms of inherited factor XIII deficiency include nosebleeds, bleeding gums, tendency to bruise, difficulties in wound healing and abnormal healing. This disease also increases the risk of intracranial hemorrhage, which is the leading cause of death in people with this disorder.  

The non-inherited form of the disease, known as acquired factor XIII deficiency, becomes evident later in life. People with the acquired form are less likely to manifest serious or potentially fatal episodes of abnormal bleeding than those with the hereditary form.  

This process is due to mutations in the F13A1 gene (coagulation factor XIII A chain), located on the short arm of chromosome 6 (6p25.1), and to a lesser extent to mutations in the F13B gene (coagulation factor XIII B chain), located on the long arm of chromosome 1 (1q31.3). These genes encode subunits (subunit A and subunit B, respectively) of the protein factor XIII of the coagulation system. This protein plays a fundamental role in the coagulation process in response to an injury. Factor XIII acts at the end of the process to strengthen and stabilize the newly formed clots, preventing additional blood loss.

At least 140 mutations in the F13A1 gene and 17 mutations in the F13B gene that result in the development of hereditary factor XIII deficiency have been described. Mutations in both genes severely reduce the amount or activity of subunit A and B of factor XIII. In most people with mutations in the F13A1 gene, the level of functional factor XIII in the bloodstream is less than 5 percent of normal. This loss of factor XIII activity weakens the new blood clots and prevents them from stopping blood loss effectively.

The acquired form of factor XIII deficiency appears when the production of factor XIII is reduced or when the body uses factor XIII faster than cells can replace it, and may result from hepatitis, cirrhosis, inflammatory bowel disease, sepsis and various types of cancer. Acquired factor XIII deficiency is generally mild, because factor XIII concentrations in the bloodstream are 20% to 70% of normal. Concentrations above 10% of normal are usually adequate to prevent episodes of spontaneous bleeding. In addition, this form can manifest itself due to the generation of autoantibodies by the immune system that attack and deactivate factor XIII. The production of autoantibodies against factor XIII is sometimes associated with diseases of the immune system, such as systemic lupus erythematosus and rheumatoid arthritis. In other cases, the trigger for the production of autoantibodies is unknown.

This disease is inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease. Some people, including the parents of people with factor XIII deficiency, have a single mutated copy of the F13A1 or F13B gene in each cell. These carriers of mutations have a reduced amount of factor XIII in their bloodstream (20% to 60% of normal), and may have abnormal bleeding after surgery, dental interventions or major trauma. However, most people who have a mutated copy of the F13A1 or F13B gene don’t have episodes of abnormal bleeding under normal circumstances, so they never get medical attention. On the other hand, the acquired form of factor XIII deficiency is not inherited and does not occur in families.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with factor XIII deficiency, by means of the complete PCR amplification of the exons of the F13A1 and F13B genes, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leukocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).