FACTOR XI DEFICIENCY (Hemophilia C, Plasma Thromboplastin Antecedent (PTA) Deficiency, Rosenthal Syndrome)
Factor XI (FXI) deficiency, also called hemophilia C, plasma thromboplastin antecedent deficiency and Rosenthal syndrome, was first recognized in 1953 in patients who experienced severe bleeding after dental extractions. Its incidence is estimated at 1 in 100,000 in the general population. In Israel, FXI deficiency occurs in up to 8% of Ashkenazi Jews because of intermarriage.
Severe FXI deficiency is inherited in an autosomal recessive pattern, meaning both parents must carry the mutated gene in order for their children to be affected. In some cases, FXI deficiency can also be inherited in an autosomal dominant pattern, meaning children with only one affected parent may inherit the condition. However, people with only one copy of the mutated gene rarely exhibit severe symptoms. Men and women are affected by FXI deficiency equally.
FXI plays an important role in the clotting cascade, which leads to a clot. It helps generate more thrombin, a protein that converts fibrinogen to fibrin, which traps platelets and helps hold a clot in place.
FXI levels in the blood do not necessarily correlate with bleeding symptoms. People with low levels may bleed less than those with higher levels. Although some patients experience frequent nosebleeds or soft tissue bleeds, others first experience hemorrhaging only after tooth extraction, such as for wisdom teeth, surgery or trauma. Further, bleeding may be delayed after these procedures. Women may not know they have FXI deficiency until they experience menorrhagia, or heavy menstrual periods, and postpartum bleeding. Joint and muscle bleeds are uncommon.
Diagnosis is made through a bleeding time test, platelet function tests, and prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests. A FXI assay helps confirm the diagnosis.
In the US there are no FXI concentrates available. However, there are two FXI concentrates manufactured in Europe, one by Bioproducts Laboratories (BPL) in the UK, the other by LFB in France, but only for limited patient use.
Fresh frozen plasma (FFP) is normally used for treatment. However, because FXI is not concentrated in FFP, large amounts of it may be needed. This can lead to blood clots, so FFP must be administered carefully.
Fibrin glue works well to maintain clots after mouth bleeds. When combined with FFP, it arrests bleeding after circumcision and hernia repair. Antifibrinolytics, such as aminocaproic acid, help control nosebleeds and bleeding after tooth extraction.