FACTOR-XIII - INHERITED AND ACQUIRED DEFICIENCY

Factor XIII (XIII), an enzyme found in plasma (present as a pro-enzyme ), platelets and monocytes, is essential for normal haemostasis. It ma y also have a role to play in the processes of wound healing and tissu e repair. Inherited XIII deficiency results in a life-long, severe ble eding diathesis which, if untreated, carries a very high risk of death in early life from intracranial bleeding. XIII is a zymogen requiring thrombin and calcium for activation. In plasma, XIII has two subunits : the 'a' subunit, which is the active enzyme, and the 'b' subunit whi ch is a carrier protein. Activated XIII modifies the structure of clot by covalently crosslinking fibrin through an epsilon(gamma-glutamyl)l ysine link. It also crosslinks other proteins, including fibronectin a nd alpha-2-plasmin inhibitor (alpha-2PI), into the clot through the sa me link. Clot modified by XIII is physically stronger, relatively more resistant to fibrinolysis and may be a more suitable medium for the i ngrowth of fibroblasts. Inheritance of factor XIII is autosomal recess ive. The majority of patients with the inherited defect show no XIII a ctivity and absence of 'a' subunit protein in plasma, platelets and mo nocytes. At the molecular level, the defect is not a major gene rearra ngement or deletion, but most likely a single point mutation which may be different in each family. Because of the severity of the bleeding diathesis, prophylaxis is desirable and has been shown to be very effe ctive as the in vivo half-life of plasma XIII is long, and low plasma levels are sufficient for haemostasis. Acquired inhibitors have been r eported in only two cases with inherited XIII deficiency. Acquired XII I deficiency has been described in a variety of diseases and bleeding has been controlled by therapy with large doses of XIII in such condit ions as Henoch-Schonlein purpura, various forms of colitis, erosive ga stritis and some forms of leukaemia. Large dose XIII therapy has also been used in an endeavour to promote wound healing after surgery and b one union in non-healing fractures. The use of XIII in these condition s remains controversial. Very rarely a bleeding diathesis results from the development of a specific inhibitor to XIII arising de novo, ofte n as a complication in the course of a disease or in association with long-term drug therapy. The bleeding diathesis in these patients is di fficult to treat.