Mafenide (Sulfamylon(TM)) inhibits plasmin fibrinolytic activity

Inflammatory fibrinolysis by plasmin or phagocyte proteases is a major cause of skin graft failure on burn wounds where the primary adherent attachment of the skin grafts is due to the glue-like action of fibrin. We investigated the potential of mafenide acetate solution, an experimental topical antimicrobial used in treating grafted burn wounds, to modify plasmin fibrinolytic activity in vitro and, thus, its potential to alter or modify the integrity of the fibrin glue critical for skin graft viability. Immobilized ¹²⁵I-fibrin monolayers were used to assay fibrinolytic activity from plasmin or from plasma activated by streptokinase or urokinase and modified by the presence of mafenide or ε-aminocaproic acid (EACA). While streptokinase-activated plasma lysed 52.7 ± 3.9% of the ¹²⁵I-fibrin, this plasma activity was more than 80% inhibitable by EACA. Mafenide acetate had no intrinsic fibrinolytic activity (1.5 ± 0.3%) nor activated plasma fibrinolytic potential (2.4 ± 0.5%), but produced significant and dose-related reduction in fibrinolytic activity (p<0.001). Other sulfonamide analogues lacking a para-methylamino reactive group had 10-100 fold less antifibrinolytic potency while lysine, like mafenide, able to compete for plasmin binding sites, could potently block fibrinolysis. Mafenide did not qualitatively alter activation of plasminogen or affect generation of complexes with α₂ antiplasmin complexes. Adding mafenide only minutes following streptokinase-activated plasma or plasmin with the fibrin substrate reduced antifibrinolytic activity, supporting the conclusion that mafenide, like EACA, can modulate the interaction between fibrin and the plasmin reactive sites and thus prevent close plasmin/fibrin apposition. The union of mafenide's potent antimicrobial activity with its antifibrinolytic potential is a fortuitous combination. The beneficial antifibrinolytic effect of mafenide may control inflammatory proteolysis, promote skin graft retention, and support wound healing.