Factor XI Deficiency (Hemophilia C)

What factor XI does

Blood clotting depends on a chain of proteins called clotting factors. Factor XI helps amplify thrombin production, especially in tissues with high levels of clot-dissolving activity (fibrinolysis), such as the mouth, nose, tonsils and urinary tract. When factor XI is low, clots form but may be weak or break down early, so bleeding after injury or surgery lasts longer or restarts.

Causes and inheritance

Factor XI deficiency is caused by changes in the F11 gene. It is inherited in an autosomal pattern, so it is not linked to the X chromosome like hemophilia A and B, and men and women are equally affected:

• Severe deficiency usually occurs when a person inherits faulty copies from both parents.
• Partial deficiency occurs with one faulty copy. Some of these people also have bleeding problems.

It is rare in the general population but common among people of Ashkenazi Jewish descent, among whom a substantial proportion carry a variant. Acquired factor XI deficiency due to antibodies is very rare.

Symptoms

Many people have no symptoms until they have surgery or an injury. When symptoms occur, they include:

• Prolonged or delayed bleeding after surgery, especially tonsillectomy, prostate or urinary procedures, and dental extractions
• Bleeding after childbirth
• Heavy menstrual bleeding
• Nosebleeds
• Easy bruising
• Blood in the urine

Spontaneous bleeding into joints and muscles, typical of hemophilia A and B, is rare.

A key feature is that bleeding tendency does not reliably match the factor XI level. Some people with very low levels bleed little, while some with mildly low levels bleed significantly. A person's own and family bleeding history is therefore important in planning care.

Diagnosis

• Bleeding history: previous surgeries, dental work, childbirth, periods and family history. Standardized bleeding questionnaires are often used.
• Coagulation tests: a prolonged activated partial thromboplastin time (aPTT) with a normal prothrombin time (PT).
• Factor XI activity level: confirms the diagnosis. Severe deficiency is generally under 15 to 20 percent of normal.
• Tests for other bleeding disorders: such as von Willebrand disease, which can occur alongside it.
• Genetic testing in some cases, and testing of family members.

Treatment

Treatment is mostly given before procedures or to treat bleeding, not on a regular basis.

• Antifibrinolytic medicines: tranexamic acid tablets or mouthwash stabilize clots. They are very effective for dental work, nosebleeds and heavy periods. They are generally avoided for bleeding from the upper urinary tract because of the risk of clots blocking the ureter.
• Fresh frozen plasma: contains factor XI. Large volumes may be needed.
• Factor XI concentrate: available in some countries, but not currently licensed in the US.
• Recombinant activated factor VII: used in selected situations, such as people with inhibitors.
• Fibrin glue and local measures for dental and surface bleeding.
• Hormonal treatments for heavy periods.

Replacement therapy carries a small risk of blood clots and, rarely, the development of inhibitor antibodies, especially in people with severe deficiency.

Planning for surgery and childbirth

• Tell every surgeon, dentist and anesthesiologist about the diagnosis.
• Plan procedures with a hemophilia treatment center or hematologist, who will base treatment on your bleeding history, factor level and the type of surgery.
• In pregnancy, factor XI levels do not rise as other factors do. Delivery should be planned with obstetric, anesthesia and hematology teams, including decisions about epidural anesthesia.

Medicines to avoid

Avoid aspirin and NSAIDs such as ibuprofen unless your hematologist agrees, as they increase bleeding risk. Use acetaminophen (paracetamol) for pain.

Outlook

Most people with factor XI deficiency live normal lives. Serious bleeding can almost always be prevented with planning before procedures. Carrying a medical alert card or bracelet helps in emergencies.

Frequently asked questions

What is factor XI deficiency?

Factor XI deficiency, or hemophilia C, is an inherited bleeding disorder caused by low levels of clotting factor XI. It mainly causes prolonged bleeding after surgery, dental extractions, injury and childbirth, as well as heavy periods and nosebleeds. Spontaneous joint bleeding is rare.

How is factor XI deficiency different from hemophilia A and B?

Hemophilia A and B are X-linked and mainly affect males, often with spontaneous bleeding into joints and muscles. Factor XI deficiency affects men and women equally, rarely causes joint bleeds, and its bleeding severity does not closely match the factor level.

How is factor XI deficiency treated?

Many people need treatment only around surgery, dental work, childbirth or injury. Options include tranexamic acid, fresh frozen plasma, factor XI concentrate where available, and fibrin glue. Heavy periods can be treated with tranexamic acid or hormones. A hematologist plans treatment in advance.

Why is factor XI deficiency common in Ashkenazi Jews?

Certain variants in the F11 gene became common in Ashkenazi Jewish populations through a founder effect, meaning they were present in a small ancestral group and passed down through generations. As a result, both carriers and people with severe deficiency are much more common in this population.