When there is an injury to a part of the body, it is important that bleeding is stopped quickly to prevent too much blood from being lost. This is achieved through the formation of a blood clot. Factor XIII, also called fibrin stabilising factor, is a vital substance involved in the formation of blood clots in the body.¹ 

A deficiency in Factor XIII means that there is not enough of this substance present in the body. This leads to a clotting disorder as the body cannot properly form a blood clot.

Though rare, affecting only around 1 in 5 million people around the world, Factor XIII deficiency can have a serious impact on a person’s quality of life. This article will go into further detail on Factor XIII deficiency, describing the signs and symptoms of this condition, how it is tested for, and the treatment options available.

What is factor XIII?

When the body is trying to stop bleeding in a certain area, a process called haemostasis is triggered. Haemostasis is a complex reaction involving many proteins, with Factor XIII being one of them. Initially, platelets, which are a type of cell in the bloodstream, clump together to form a plug in the broken blood vessel. A series of chemical reactions then take place, which end in the formation of a mesh made out of a substance called fibrin. The fibrin mesh combines with the platelet plug to form a blood clot. Factor XIII is vital in this final step as it stabilises the fibrin mesh. This prevents the clot from being broken down rapidly by the body. Without a stable clot, bleeding can continue for prolonged periods of time and can become life-threatening.²

Causes of factor XIII deficiency

Factor XIII deficiency is usually inherited and congenital, meaning it is present at birth. It is an autosomal recessive disorder. This means that both parents must have the disease-causing mutation for it to get passed on to the baby. If a baby receives only one faulty copy of the gene, it will not be affected but will instead be a carrier of the condition. This means that Factor XIII deficiency is more commonly encountered in families that marry blood relatives.  

However, Factor XIII deficiency can also be acquired. This is when a condition is not present at birth but develops over time. It could occur due to certain autoimmune conditions, such as lupus and rheumatoid arthritis. It is also associated with inflammatory bowel disease, surgery, sepsis, leukaemia, liver disease and some medications.²  

Symptoms of factor XIII deficiency

Without the ability to form stable blood clots, people affected by Factor XIII deficiency typically have various symptoms associated with bleeding. This includes:² 

• Umbilical bleeding - This is the most common symptom of Factor XIII deficiency, with around 80% of affected babies experiencing umbilical cord stump bleeding. Those with a severe deficiency are more likely to have bleeding in the early weeks of life. 
• Prolonged wound healing 
• Heavy periods
• Recurrent spontaneous miscarriage
• Easy bruising
• Bleeding gums
• Muscle or joint bleeds
• Major postoperative bleeding 
• Intracranial bleeding - This is when there is bleeding within the skull. In people affected by Factor XIII deficiency, this can occur without prior trauma. It is the most severe manifestation of Factor XIII deficiency and can be life-threatening.

If you are having frequent or prolonged bleeding episodes, it is important to contact your healthcare provider as soon as possible.  

Diagnosis

Factor XIII can be diagnosed prenatally (before birth) if there is a suspicion of it being passed down to the baby from parents who are carriers or if there is a family history of the condition. The options for prenatal testing include chorionic villus sampling, where a sample of cells from the placenta is extracted and analysed, or amniocentesis, which involves testing a sample of cells collected from the amniotic fluid. 

There are multiple diagnostic tests that can be performed to diagnose Factor XIII deficiency. These include:² 

• Blood tests - These tests can measure the time it takes for a blood clot to form and analyse how stable the blood clot is
• Genetic testing - This type of testing can check if you have a gene mutation that is known to cause Factor XIII deficiency
• Quantitative assays - These tests can check the level of Factor XIII in your body
• Imaging - CT scans or an MRI can be used to check for bleeding in joints and other tissues of your body. 

Treatment

If your healthcare provider is concerned about low levels of Factor XIII, they may recommend prophylactic treatment. This is to prevent significant bleeding before it actually happens. Replacement Factor XIII is usually administered in the form of an injection of Factor XIII concentrate. 

If an affected person requires surgery for another health condition, additional injections or special medications may be required to prevent excessive post-operative bleeding.³ Your healthcare provider should inform you of the precautionary actions that need to be taken beforehand. 

Another instance where further dosages may be required is during pregnancy and before childbirth. This is done to prevent miscarriages and post-partum bleeding.³ It is important that the entire healthcare team is involved in managing this condition. 

The Haemophilia Society recommends regular checkups with a specialist to stay on top of your condition. In most cases, where adequate treatment is being administered, affected individuals should be able to carry out most normal daily activities.

It is also important to be aware of the signs of a bleed so that you can seek urgent medical attention when required. Wearing a medical identity bracelet is beneficial as it can help healthcare providers provide tailored emergency treatment without delays. 

It is also advised that certain activities, such as contact sports, are avoided as they may pose a risk of injury and subsequent life-threatening intracranial bleeding.³ 

Summary

Factor XIII deficiency is a rare blood clotting disorder. It is characterised by symptoms of excessive external and internal bleeding due to a fault in the blood clotting mechanism. Blood tests and genetic tests can be used to diagnose Factor XIII deficiency. If you are diagnosed with this condition, you will require lifelong treatment and monitoring to avoid life-threatening bleeding. The gold standard treatment of Factor XIII deficiency is prophylactic injections of Factor XIII concentrate to compensate for the low levels of the protein in your body. If you are worried that you are affected by this condition, you should discuss your concerns with your healthcare provider as soon as possible.