Haemophilia C (factor XI deficiency): inheritance, bleeding symptoms and care

Blood clotting needs a series of proteins called clotting factors to work in sequence. Haemophilia in the usual sense, as the NHS describes, is caused by a lack of clotting factor VIII (haemophilia A) or factor IX (haemophilia B). Haemophilia C is the older name for a different disorder, a deficiency of clotting factor XI.

The National Bleeding Disorders Foundation, a US organisation, explains that factor XI deficiency is also called haemophilia C, plasma thromboplastin antecedent deficiency and Rosenthal syndrome, that it was first recognised in 1953 in patients who bled severely after dental extractions, and that factor XI helps generate more thrombin, which leads to a firm clot.

The Haemophilia Society notes that around one in 2,000 people in the UK have a diagnosed bleeding disorder, that most are inherited, and that many people are undiagnosed or diagnosed late because of a lack of understanding of these rare conditions.

The Haemophilia Society explains that bleeding disorders are generally inherited, passed from parent to child in their genes, so you would have the condition from birth. It lists the situations that can arise when parents pass on a clotting factor gene fault: one parent a carrier and the other with normal genes, both parents carriers, one parent with the condition and one with normal genes, and so on.

For factor XI deficiency in particular, the US source says severe deficiency is inherited in an autosomal recessive pattern, meaning both parents must carry the changed gene. In some cases it can also be inherited in an autosomal dominant pattern, meaning a child with only one affected parent may inherit the condition, although people with only one copy rarely have severe symptoms.

Because it is not on the X chromosome, men and women are affected equally. The Haemophilia Society adds that as many as a third of bleeding disorder diagnoses have no known family history and can be the result of a random gene change, so a diagnosis can arrive out of the blue.

The Haemophilia Society lists symptoms common to bleeding disorders: easy bruising and heavy, painful periods lasting longer than a week. Others occur in most but not all, such as bleeding into joints or muscles, or for longer than normal after minor or major surgery or after dental work.

The US source gives a more specific picture for factor XI deficiency. Levels do not necessarily correlate with bleeding symptoms, so people with low levels may bleed less than those with higher levels. Some people have frequent nosebleeds or soft tissue bleeds, while others first bleed only after tooth extraction, surgery or injury, and the bleeding may be delayed. Women may not know until they have heavy periods or bleeding after childbirth, and joint and muscle bleeds are uncommon.

This unpredictability is why a history of bleeding, and not just a laboratory result, guides decisions about care.

The Haemophilia Society says that depending on the type of bleeding disorder and family history, people may know from birth, or be diagnosed as a young child, or only as an adult after heavy bleeding with a tooth removal or an operation. Blood tests before surgery may pick up a problem.

It adds that blood tests are needed for a firm diagnosis, that these are not generally routine tests and may have to be carried out in a specialist centre, and that a genetic test may be needed to find the exact change in the genes.

The US source says diagnosis involves screening clotting tests including the prothrombin time and the activated partial thromboplastin time (aPTT), with a factor XI assay to confirm. Anyone who bleeds unusually after a procedure, or has heavy periods and a family history, should ask their GP about referral to a haematology service.

The Haemophilia Society describes treatment options for rare bleeding disorders as a group. Factor concentrates replace the missing factor and are the ideal treatment where available, but they are not available for all disorders. Fresh frozen plasma is used where no concentrate is available, and tranexamic acid helps stop clots breaking down and is useful before a tooth extraction, planned surgery or for nosebleeds and heavy periods. Fibrin glue can be applied to wounds or after dental work, and hormonal contraception can help control heavy periods.

For factor XI deficiency the US source says that fresh frozen plasma is normally used, that large amounts may be needed which can lead to clots, and that two factor XI concentrates are made in Europe, one in the UK and one in France, but only for limited patient use. Antifibrinolytics and fibrin glue help control mouth and nose bleeds. Whether a particular treatment is available should be checked with the treating haemophilia centre.

People with a rare bleeding disorder should tell dentists and surgeons about the diagnosis in advance so that a plan can be made with the haematology team.

The NHS advice on haemophilia says that for most bleeding you need to get medical help. Bleeding that does not stop, a heavy bleed after a tooth extraction or injury, or bleeding after an operation should be assessed quickly through the haemophilia or haematology centre, NHS 111 or A&E. Call 999 for severe bleeding, a head injury or collapse.