Laboratory and Molecular Diagnosis of Factor XI Deficiency

The prevalence of factor XI (FXI) deficiency is 1 per 10 to 20,000 in the general population, much higher than that reported in most texts. The prevalence is higher in Ashkenazi Jews where it is about 1:20. Clinically, FXI deficiency presents as a mild bleeding disorder mostly associated with posttraumatic or postsurgical hemorrhages or unexplained minor bleeding. It is often discovered due to incidental finding of a prolonged activated partial thromboplastin time (aPTT) on routine laboratory screening. FXI deficiency is an autosomal recessive bleeding disorder with many causative F11 gene defects. Diagnosis is based on FXI activity, antigen levels, and molecular diagnostics. As FXI levels do not correlate with bleeding symptoms, identification of pathogenic genetic variants may be a more accurate predictor of bleeding risk and therefore aid in the clinical management of the patient. Two variants in the F11 gene account for most cases found in the Jewish and Arab populations. Patients with FXI deficiency can develop inhibitors to FXI although spontaneously acquired inhibitors are extremely rare. We will discuss laboratory and molecular assays used to diagnose FXI deficiency as well as interferences that can complicate diagnosis including new anticoagulants and acquired FXI inhibitors.