Severe Wound Healing Impairment in a Patient with Dysfibrinogenaemia

Abstract

Fibrinogen has a principal role in blood clot formation. It is a soluble protein that is converted to fibrin and polymerizes into insoluble fibrin fibres forming a clot-stabilizing network. This is further strengthened by activated factor XIII (FXIIIa) via cross-linking and incorporation of α2-antiplasmin and thrombin activatable fibrinolysis inhibitor (TAFI). Fibrinogen is synthesized in hepatocytes and composed of three pairs of different polypeptide chains (Aα, Bβ, γ), interconnected via disulphide bridges. Each chain is encoded by a single gene (FGA, FGB and FGG). In congenital dysfibrinogenaemia, a qualitative defect is caused by mutations within any of these genes. According to the online database of dysfibrinogenaemias, 1,215 cases are reported at present: 626 with a defect in the Aα chain, 154 in the Bβ chain, and 435 in the γ chain.[1] The clinical spectrum of this disorder is heterogeneous: 26% of the patients have a bleeding tendency, 21% of the patients have a thrombotic tendency, and 53% of the patients are asymptomatic.[2] [3] [4] Dysfibrinogenaemia can thus lead to both bleeding and thrombosis, illustrating the versatile functions of fibrinogen in coagulation. Furthermore, fibrinogen is important for wound healing. The fibrin network serves as a provisional scaffold at the site of injury and supports cell proliferation and migration.[5] This role of fibri(noge)n in tissue repair is illustrated by the use of fibrin sealants to promote wound healing,[6] although this fibrin concentration is much higher than in physiological conditions. Delayed wound healing and/or wound dehiscence is a clinical feature in FXIII deficiency due to decreased cross-linking of fibrin and decreased linking to other proteins.[7] Surprisingly, impaired wound healing is not a well-known feature in congenital dysfibrinogenaemia. We here report a case of severely impaired wound healing in a man with dysfibrinogenemia due to fibrinogen Longmont, a heterozygous dysfibrinogenaemia causing impaired polymerization.