Factor XI deficiency (Hemophilia C)

Factor XI (pronounced factor 11) deficiency is an inherited bleeding disorder. It also goes by the name of hemophilia C.

Factor XI is a trace protein in the blood. It is produced in the liver. It plays a role in the coagulation cascade, the chain reaction that is set in motion when there is an injury to a blood vessel. It appears that factor XI helps in the activation of factor IX (pronounced factor 9), another blood protein important in the clotting process.

For more information on blood clotting, see The clotting problem in hemophilia.

In factor XI deficiency, the level of factor XI in the blood is lower than normal. People are likely to suffer from bleeding when the factor XI levels fall below 15% of normal. However, after surgery, bleeding can occur in people whose factor XI levels are as high as 50-70% of normal.

No. Factor XI deficiency is generally quite rare. It affects about 1 in 100,000 people. More than 400 cases have been identified in the United Kingdom alone.

The disorder is particularly common among Ashkenazi Jews, of Eastern European origin. It is estimated that 8% of the people in this ethnic group carry the defective factor XI gene.

Factor XI Deficiency is an hereditary disease. This means that it is passed on from the parents to the child at the time of conception. It is an 'autosomal recessive' disorder. This means that both parents must carry the defective gene to be able to pass it on to their children.

However, Factor XI Deficiency seems to be different from other factor deficiencies which are passed on in this way. Some people have bleeding problems when only one of their parents has the gene which causes Factor XI Deficiency.

Factor XI Deficiency affects males and females in equal numbers.

Symptoms are different from person to person.

The link between the level of factor XI and the seriousness of bleeding problems is not clear. Even members of the same family have different bleeding symptoms. This makes predicting when bleeding will happen very hard. It is not known why symptoms vary so much from person to person. As a general rule:

Some doctors think that people with more serious symptoms may also have low levels of other clotting proteins, like factor VIII and von Willebrand factor.

Symptoms of factor XI deficiency are:

• persistent bleeding after surgery, especially when fibrinolysis is a particular problem (for example, tonsils, prostate, mouth, womb)
• persistent bleeding after trauma (a serious injury)
• bleeding after tooth extractions
• heavy and prolonged bleeding during menstruation (menorrhagia).

Spontaneous bleeds (bleeding with no clear cause) are rarely seen in factor XI deficiency. Nor are bleeds into joints, soft tissues and muscles.

If a bleeding disorder is suspected, doctors will do a number of tests to find out:

• if the person has a bleeding disorder and
• if so, what particular bleeding disorder it is.

With factor XI deficiency, the tests are:

There are four treatments used to control or prevent bleeding in factor XI deficiency. Each has advantages and disadvantages.

Fresh frozen plasma (FFP)

Advantages

• It is effective for mild bleeding episodes.
• It does not increase the risk of unwanted blood clots in the bloodstream (especially important for older people with a history of heart disease, pregnant women and people with cancer).
• It will soon be available in virally attenuated forms (this means that viral inactivation methods using solvent detergent will kill known viruses like HIV, hepatitis B and hepatitis C).

Disadvantages

• The volume of plasma is quite large and the amount of factor XI in the plasma is quite small. For serious bleeding or for surgery, the body's circulatory system may be overloaded by too much plasma before sufficient factor XI is infused to control the bleeding.
• Until virally attenuated FFP is introduced, the risk of transmitting viruses like HIV, hepatitis B and hepatitis C, while small, is present.

Factor XI Concentrates

Advantages

• This factor concentrate, also made from human plasma, contains only factor XI. It is treated to kill known viruses, like HIV, hepatitis B and hepatitis C.
• It can be administered easily in small volumes. Therefore, it does not have the problem of large volumes of plasma causing an overload to the body's circulatory system. As a result, it is very effective in cases of serious bleeding or surgery.

Disadvantages

• For reasons that are not well understood, the use of factor XI concentrate raises the risk of blood clots forming in the bloodstream where they are not wanted (thrombosis). The risk is highest in older people with a history of heart disease, pregnant women and people with cancer.

Fibrin glue

Fibrin glue is applied to external wounds, for example, in the mouth after a tooth extraction. It is applied with two syringes. One holds calcium and thrombin. The other holds fibrinogen, factor XIII and aprotonin.

Advantages

• It is very effective in dental work.
• It can be used alone or with fresh frozen plasma for certain types of surgery (circumcision, hernia ...).
• It is entirely safe.

Disadvantages

• It is not effective for major bleeding or surgery.

Antifibrinolytic drugs (Cyklokapron, Amicar)

Cyklokapron (tranexamic acid) and Amicar (aminocaproic acid) are drugs that help to hold a clot in place once it has formed. They act by stopping the activity of an enzyme, called plasmin, which dissolves blood clots.

For tooth extractions in people with factor XI deficiency, they are often effective alone, without the use of blood products.

They can be used to hold a clot in place in mucous membranes such as:

• the inside of the mouth
• the inside of the nose
• inside the intestines (the gut)
• inside the uterus (the womb).

Advantages

• They are easy to use.
• They are safe.

Disadvantages

• They are not effective for major internal bleeding or surgery
• They can cause clotting throughout the body.