Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade.
It is a serine protease.
Factor XI is encoded by the F11 gene in chromosome 4.
Factor XI (FXI) is produced by the liver and circulates as a homo-dimer in its inactive form.
Factor XI plays a critical role in pathologic thrombosis, but is less involved in normal hemostasis.
It suggested inhibiting factor XI could reduce pathological thrombosis without substantially impairing hemostasis.
The plasma half-life of FXI is approximately 52 hours.
Zymogen factor XI is activated into factor XIa by factor XIIa (FXIIa), thrombin, and FXIa itself; due to its activation by FXIIa.
FXI is a member of the contact pathway including high molecular weight ,kininogen, prekallikrein, factor XII, factor XI, and factor IX.
People with genetically reduced levels of factor XI have a low risk of venous thromboembolism and ischemic stroke without an increased risk of spontaneous bleeding.
Patients with elevated factor XI levels are an increased risk for thrombosis.
Factor XIa activates factor IX by selectively cleaving peptide bonds.
Factor IXa, in turn, forms a complex with Factor VIIIa (FIXa-FVIIIa) and activates factor X.
Physiological inhibitors of factor XIa include protein Z-dependent protease inhibitor .
Although synthesized as a single polypeptide chain, FXI circulates as a homodimer.
Typical plasma concentrations of FXI are 5 μg/mL, corresponding to a plasma concentration (of FXI dimers) of approximately 30 nM.
The FXI gene is found on chromosome 4q32-35.
Deficiency of factor XI causes the rare hemophilia C, which mainly occurs in Ashkenazi Jews and is believed to affect approximately 8% of that population.
Less commonly, hemophilia C can be found in Jews of Iraqi ancestry and in Israeli Arabs.
The condition has been described in other populations at around 1% of cases.
It is an autosomal recessive disorder.
There is little spontaneous bleeding, but surgical procedures may cause excessive blood loss, and prophylaxis is required.
Low levels of factor XI occur in many other disease states, including Noonan syndrome.
High levels of factor XI have been implicated in thrombosis.
Pharmacological inhibitors of factor XI that are under clinical development.
Abelcimab is a an inhibitor of factor XI and XIa , a human monoclonal antibody that binds with high affinity and potency to increase the inactive and active forms of factor XI.
Abelcimab has both rapid and profound effect on the levels of fact, the XI win an hours after treatment.
Abelcimab reduces free, factor XL levels from baseline by a median of 97% at three months.