Factor XIII: Congenital Deficiency Factor XIII, Acquired Deficiency, Factor XIII A-Subunit, and Factor XIII B-Subunit

Abstract

Factor XIII (FXIII) is a transglutaminase consisting of 2 catalytic A subunits and 2 noncatalytic B subunits in plasma. The noncatalytic B subunits protect the catalytic A subunits from clearance. Congenital FXIII deficiency may manifest as a lifelong bleeding tendency, abnormal wound healing, and recurrent miscarriage. Acquired FXIII deficiency, with significant reductions in FXIII levels, has been reported in several medical conditions. The routine screening tests for coagulopathies-prothrombin time, activated partial thromboplastin time, and thrombin time-do not show abnormalities in cases of FXIII deficiency. A quantitative, functional, FXIII activity assay that detects all forms of FXIII deficiency should be used as a first-line screening test. Treatment consists of recombinant FXIII or FXIII concentrate. If these are unavailable, then fresh-frozen plasma and cryoprecipitates may be used. Factor XIII has a long half-life; therefore, the patients can lead near-normal lives with regular replacements. Patients with acquired FXIII deficiency with inhibitors need immunosuppressive therapy in addition to factor replacements.

Effects of factor XIII deficiency on thromboelastography. Thrombelastography with calcium and lysis by addition of streptokinase is more sensitive than solubility tests

“…Congenital FXIII deficiency, a rare autosomal recessive condition, and patients often suffer from umbilical stump bleeding, subcutaneous bleeding, muscle hemorrhage, postoperative hemorrhage, and potentially fatal intracranial hemorrhage 1,4,12. The case we described here suffered from umbilical stump bleeding, and subcutaneous and muscle bleedings at very early age.…”

“…Upon thrombin cleavage of Arg37-Gly38 in the A- subunit and calcium presence B- subunit dissociates from A subunit, the cysteine active site (Cys314 interacting with His373 and Asp396) in the central core is exposed and FXIII-A becomes activated. FXIII-A has a transglutaminase action that produces a gamma glutamyl epsilon lysine crosslinking between fibrin fibers, stabilizing and conferring them viscoelastic resistance to shear forces and also to increase the resistance to fibrinolysis by plasmin, due to the crosslinking of fibrin and α2 antiplasmin 1–3…”

Real-time measurement of thrombin generation using continuous droplet microfluidics

“…23 In addition, in association with thrombomodulin, thrombin can be suppressed by thrombin activatable fibrinolysis inhibitor, which delays plasmin-mediated dissolution of the fibrin clot. 24,25 After the addition of the Innovin solution, GPRP peptide solution was added; GPRP slows clot formation without affecting thrombin generation. 26 Then, the activated plasma sample was mixed with different concentrations of the thrombin fluorogenic substrate I-1140 in the waterin-oil droplets.…”

Clinical influence of preoperative factor XIII activity in patients undergoing pancreatoduodenectomy

“…FXIII is one of the main contributors during the final phase of the clotting cascade because it cross-links fibrin monomers. 8,9 In clinical settings, FXIII deficiency occurs as a congenital condition as well as an acquired condition. Highly invasive surgeries that are accompanied by massive bleeding are among the most common medical conditions that elicit acquired FXIII deficiency due to a decreased synthesis and over-consumption of FXIII.…”

“…[3][4][5][6][7] Factor XIII (FXIII) is a key factor that functions at the end of the coagulation cascade by cross-linking fibrin monomers into stable polymers and counteracting fibrinolytic degradation. 8,9 FXIII also plays an important role in wound healing. 10 Some studies have reported associations of FXIII activity with perioperative bleeding in cardiac, 11,12 gastrointestinal, 13 and neurologic surgeries.…”