Factor XI deficiency (also called plasma thromboplastin antecedent, PTA, deficiency) was originally identified as hemophilia C by Rosenthal and coworkers in 1953. Deficiency in factor XI is inherited as an autosomal condition with clinical manifestations seen in both homozygotes and heterozygotes. Twenty distinct mutations and deletions have been identified in patients suffering from factor XI deficiency all of which are associated with low levels of factor XI and low activity. Most of the mutations, as well as afflicted individuals, are of Jewish with the first patients identified being of Ashkenazi Jewish descent. The frequency of this disorder in Ashkenazi Jewish persons in as high as 1 in 190. Bleeding tendency in factor XI deficient patients is less severe and much more variable than in hemophila A or hemophilia B.
Bleeding in factor XI deficiency is most often triggered by surgery or trauma. Spontaneous bleeding, as occurs in both hemophilia A and B, is very rare in factor XI deficiency. Excessive bleeding from sites of injury can persist for several hours to days. However, there is a variability to the severity of bleeding where some individuals with levels of factor XI that are <1% of normal do not bleed excessively despite trauma. This phenotypic phenomenon is the result of both the inherited genotype as well as the site of injury. Bleeding due to surgery or trauma on tissues with a high fibrinolytic, such as the oral cavity, is the most severe.
The factor XI gene (symbol F11) is located on chromosome 4q35 spanning 23 kbp and composed of 17 exons encoding a 625 amino acid preproprotein with a leader peptide of 18 amino acids. The mature protein circulates in the blood as a disulfide bonded homodimer of 1214 amino acids. The protein is comprised of a heavy of 369 amino acids and a light chain of 238 amino acids. The light chain contains the catalytic domain of factor XI which is similar to the catalytic domain in other members of the trypsin family of serine proteases.