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HEMOPHILIA.ORG > BLEEDING DISORDERS INFO CENTER > TYPES >
FACTOR XI DEFICIENCY


Factor XI Deficiency
(Hemophilia C, Plasma Thromboplastic Antecedent
or Rosenthal Syndrome)

What Is It?
Factor XI deficiency is a very rare bleeding disorder, occurring in an estimated one in 100,000 Americans. It has more variable bleeding tendencies than hemophilia A and B, and people with the disorder usually don't bleed into joints and muscles, as in hemophilia. The disorder is usually only mild, and is typically provoked by surgery.

Factor XI is a protein that helps blood clot and is activated by thrombin. Deficiencies occur rarely, and in all racial groups, but it is particularly common in Ashkenazi Jews. These are primarily Jews of eastern European ancestry, and the relationship is presumably because intermarriage within this closed group, generation after generation, allowed the defective gene to surface more frequently.

In the US, most cases are found in New York and Los Angeles. Approximately 200 cases of factor XI deficiency have been reported since it was identified in 1953. Ever since, the deficiency has been a puzzle because of its variable bleeding symptoms in different patients—even at different points in their lives and with different injuries and surgeries.

Three different genetic mutations have been identified, and a person's particular mix of these influences their bleeding tendencies.

Inheritance Pattern
The disorder is not sex-linked as is hemophilia. It affects both males and females with equal frequency. It is an autosomal recessive disorder, which means that if the clotting defect is inherited from a parent, the child will be a genetic carrier of the condition, but may or may not have symptoms. Severity of symptoms can be unpredictable between members and carriers of the same family.

Symptoms and Diagnosis
Most patients with factor XI deficiency have little or no bleeding. Often there is no correlation between bleeding episodes and the level of factor. Unlike hemophilia, there is no spontaneous bleeding into joints and muscles. Many patients are difficult to classify because some bleed excessively after some surgical procedures but not others. Even in individual patients, bleeding tendencies can be unpredictable. People with factor XI deficiency should know that surgical procedures involving areas with high contents of plasminogen activator, a substance that breaks up clots, are associated with prolonged bleeding. These include dental extractions, tonsillectomies, surgery in the urinary and genital tracts and nasal surgery.

If you have factor XI deficiency, chances are your symptoms are milder than those of either hemophilia A or hemophilia B, and there may be no strong relationship between your factor XI levels and bleeding complications. You may be prone to bruising, nose bleeds or blood in your urine. Prolonged bleeding after childbirth can occur. You are not likely to bleed spontaneously, and hemorrhaging is usually a problem only after an injury or surgery. Joint bleeds are uncommon, but delayed bleeding (starting an unexpectedly long time after an injury) may be a problem.

Factor XI deficiency varies often in clinical presentation. One reason is that some patients have additional coexisting blood abnormalities, such as von Willebrands disease.

Because it's so common among Ashkenazi Jews (found in around 8% of the population), it is a common practice in Israel to screen every surgery patient for factor XI deficiency.

A specific factor XI assay is required for diagnosis.

Treatments
People with factor XI deficiency may need specific therapy for surgery, accident trauma and dental extractions. Several treatments are available, including fresh frozen plasma, factor XI concentrates, fibrin glue, antifibrinolytic drugs and desmopressin. Aminocaproic acid works well following tooth extractions. Each has advantages and risks that should be considered.

There is no commercially available factor XI concentrate currently licensed for use in the US at this time.

In the event of major surgery, factor XI-deficient patients with levels less than 10% of normal may be treated with plasma prior to surgery, or plasma may be infused during surgery. The plasma half-life of factor XI is approximately 80 hours.

Complications
Because the deficiency is so unpredictable, clinical management of it is difficult. Bleeding may occur days after a dental extraction or a surgery. It's also very difficult to identify in advance individuals with the deficiency who are likely to bleed.

Factor XI antibodies can cause significant inhibition and clinical problems. So it is important before elective surgery where plasma products are used that all patients are screened for inhibitors. Fresh frozen plasma carries a risk of infectious viruses and can be avoided by using heat-treated concentrate or solvent-detergent plasma. Note that factor XI concentrate is not commercially available in the US.

Because considerable amounts of plasma are needed to maintain the factor XI level, it stresses the heart and can cause side effects such as migraines. Other plasma contaminants can cause allergic reactions.

Disclaimer
The information contained on the NHF web site is provided for your general information only. NHF does not give medical advice or engage in the practice of medicine. NHF under no circumstances recommends particular treatment for specific individuals and in all cases recommends that you consult your physician or local treatment center before pursuing any course of treatment.
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