Factor XIII

Factor XIII (FXIII) is also known as Fibrin Stabilizing Factor. Fibrin monomers produced by the action of thrombin on fibrinogen spontaneously polymerize to form the initial fibrin clot. However, the fibrin stands are held together by hydrophobic bonds and are very unstable. This clot is subsequently stabilized by FXIII, a transglutaminase enzyme which catalyzes covalent bonds between adjacent strands of monomeric fibrin.

FXIII is found in plasma as a 320 kD tetramer composed of two 75 kD A-subunits linked non-covalently to two 80 kD B-subunits. The active site resides on the A subunit, while the B subunit functions as a carrier.

Congenital FXIII deficiency is extremely rare, with an estimated prevalence of only 1 in 5 million. There are less than 200 reported cases worldwide. The disorder is inherited as an autosomal recessive trait, that affects both males and females equally. There is often a history of parental consanguinity.

Homozygous FXIII deficiency results in a life-long bleeding tendency. Typically, a clot forms normally after injury or surgery but subsequently breaks down with further bleeding. Easy bruising, prolonged bleeding from superficial wounds and poor wound healing are common. A common early manifestation is bleeding from the umbilical stump and there is a high risk of intracranial haemorrhage, which may arise spontaneously and without previous head injury. Recurrent spontaneous abortion has been reported in affected females. Acquired FXIII deficiency due to the development of inhibitory antibodies has been reported.

It is important to note that routine hemostatic evaluation with PT and APTT is normal in these patients and the diagnosis must be specifically excluded. The Hemostasis and Thrombosis Laboratory utilizes a simple screening test for gross FXIII deficiency in which a thrombin-induced fibrin clot is suspended in a solution of 5M urea. Normal fibrin remains insoluble for weeks or months, but in FXIII deficiency the clot is unstable and dissolves rapidly. Abnormal results (a soluble clot) will be obtained only in severe (<1%) FXIII deficiency.