Factor XI Deficiency

Also known as: Plasma Thromboplastin Antecedent (PTA) Deficiency; Rosenthal syndrome.

Factor XI deficiency is a autosomal recessive bleeding disorder characterised by easy bruising; and abnormal bleeding after surgery and trauma; and menorrhagia and post-partum haemorrhage in women. Although symptoms vary widely, the condition is usually mild and can be treated effectively.

Presentation

Most patients with factor XI deficiency have little or no symptoms at all, the disorder may manifest as an incidental laboratory finding. Spontaneous bleeding is rare in all groups.

Common symptoms include:

  • Epistaxis.
  • Easy bruising
  • Menorrhagia.
  • Abnormal bleeding during or after surgery, injury, or childbirth.
  • Abnormal bleeding is often experienced during dental extraction
  • May present with bleeding manifestations at circumcision.

Factor XI levels in the blood do not correlate with or act as predictor of bleeding risk. Within both the patient and the family, highly variable and unpredictable bleeding patterns occur.

Please click on the titles to open and close the following information sections.

  • Factor XI deficiency is caused by genetic variants in a gene located on chromosome 4 that controls the production of protein Factor XI (FXI).
  • This protein produced by the liver, and found in the blood, plays an important role in the clotting cascade. It helps to generate more thrombin – a protein that converts fibrinogen to fibrin, which traps platelets and helps hold a clot in place.
  • Two predominant genetic variants, type II and III cause the FXI deficiency in patients of Ashkenazi Jewish (AJ) descent. Patients with FXI deficiency who are of non-AJ heritage are more likely to have other variants.
  • The type III variant is an amino acid substitution resulting in a missense variant. This results in impaired dimerization and secretion of the FXI molecule.
  • The type II variant causes premature chain termination and results in very low levels of circulating FXI.
  • Even in severe deficiency, the bleeding tendency is usually mild, generally without spontaneous bleeding, and haemarthrosis is not a feature.
  • All groups have more bleeding with surgery involving surfaces with fibrinolytic activity (mouth, tonsils, urinary tract) compared with other surgery.
  • The incidence of factor XI deficiency in the general population is estimated to be 1:1,000,000.
  • In Ashkenazi Jews, the carrier frequency is estimated to be 1 in 12; with a disease incidence of approximately 1:575 (one of the commonest genetic disorders in this group).
  • Factor XI deficiency is also common in the French Basque population.
  • The diagnosis is suggested by a prolongation of the activated partial thromboplastin time.
  • A factor XI assay is used to confirm a diagnosis.

Gene Specific:

  • Genetic testing for variants in the F11 gene that cause factor XI deficiency is now readily available through specialist laboratories attached to haemophilia centres. In some cases where the factor XI assay gives borderline results it may be the only way of making the diagnosis.
  • In the UK the standard treatment is tranexamic acid for milder disease and/or FXI concentrate for more more severe disease.
  • Fresh Frozen plasma (FFP) is not normally used for treatment as factor XI is not concentrated in FFP, large amounts may be needed, which can lead to complications.
  • Antifibrinolytics – such as tranexamic acid, helps control nosebleeds and bleeding after tooth extraction.
  • Fibrin glue works well to maintain clots after mouth bleeds and may serve as an alternative to the standard management of tranexamic acid mouthwash. Tranexamic acid or fibrin glue can arrest bleeding after circumcision and hernia repair.
  • Menorrhagia in women with factor XI deficiency may be controlled with OCP, IUD’s or antifibrinolytic drugs.

Family members should be referred for further investigation and carrier testing as appropriate.

  • Most patients with FXI deficiency have mild if any symptoms and the condition is not known to affect lifespan.
  • In undiagnosed patients with FXI deficiency people, there is a small possibility of life-threatening bleeding after surgery or trauma.
  • Development of FXI inhibitors (IgG) occurs at a rate of approximately 5% in patients with severe (<1%) FXI deficiency, after exposure to exogenous FXI (usually via plasma products).
  • This is a recognized complication of replacement therapy and should be evaluated for patients before a planned invasive procedure.
  • Epidemiological data has shown that high levels of FXI are associated with an increased risk of venous thrombosis. However, data suggests that low levels may actually protect from venous thrombosis.
  • For patients exhibiting features of factor XI deficiency, initial referral would usually be to a haematologist. For Jewish patients, it is important to note the ancestry and higher prevalence of FXI deficiency in the Jewish population.
  • In cases where there are very strong indicators that FXI deficiency is a likely diagnosis, it is possible to send a clotting sample for testing.
The Haemophilia Society

The Society is the only national and independent organisation for all people affected by bleeding disorders. It provides information and support for all people affected by bleeding disorder, including Factor XI deficiency, and represent their interests. Tel: 020 7831 1020 Freephone: 0800 018 6068

Haemophilia Society Facebook Page

A facebook page for the Haemophilia Society which includes support resources.

The United Kingdom Haemophilia Centre Doctors’ Organisation

The UKHCDO is an association of medical practitioners who work within the Haemophilia Centres of England, Scotland, Northern Ireland or Wales. This link provides contact information for all the different NHS Haemophilia centres across the UK.

Circumcision London

Dr Martin Harris is a mohel and surgeon who carries out circumcisions with knowledge and experience of carrying out circumcisions in families with Factor XI deficiency. In collaboration with the Royal Free centre he was involved in developing a protocol for the management of circumcision on the male infants of Factor XI deficient patients. Telephone: 020 8209 2401

OMIM: #612416

Written by: Dr Jacky Megitt, Jnetics researcher. Approved by: Dr Keith Gomez, Consultant Haematologist, Royal Free Hospital Last review: 19.06.2018

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