Download PDF
Thromb Haemost 1988; 59(03): 440-444
DOI: 10.1055/s-0038-1647512
Original Article
Schattauer GmbH Stuttgart

Mafenide (Sulfamylon™) Inhibits Plasmin Fibrinolytic Activity

Daniel J Weisdorf
1   The Department of Medicine, Division of Hematology, University of Minnesota, Minneapolis, Minn., USA
,
Jeffrey H Aldridge
2   The Department of Surgery, Division of Plastic and Reconstructive Surgery, University of New Mexico, Albuquerque, N. Mex., USA
› Author Affiliations
Further Information

Publication History

Received 30 July 1987

Accepted after revision 04 February 1988

Publication Date:
29 June 2018 (online)

Also available at
  PDF Download Permissions and Reprints

Summary

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 gluelike 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 plasmin 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.

Keywords

Fibrinolysis - Plasmin - Mafenide
 

  • References

  • 1 Collen D. On the regulation of control of fibrinolysis. Thromb Haemostas 1980; 43: 77-89
    PubMedSearch in Google Scholar
  • 2 Shafter KE, Saritoro sA, sober BE. Monitoring activity of fibrinolytic agents. Am J Med 1984; 76: 879
    CrossrefPubMedSearch in Google Scholar
  • 3 Thvis MJ, Thornton JW, Harney JH, Woodroof EA, Bartlett RH. Graft adherence to de-epithelialized surfaces. A comparative study Ann Surg 1976; 184: 594-600
    CrossrefPubMedSearch in Google Scholar
  • 4 Plow EE, Edgington TS. An alternative pathway for fibrinolysis: I. The cleavage of fibrinogen by leukocyte proteases at physiologic pH. J Clin Invest 1975; 56: 30-38
    CrossrefPubMedSearch in Google Scholar
  • 5 Teh BT. Why do skin grafts fail. Plast Reconstr Surg 1979; 63: 323-332
    CrossrefPubMedSearch in Google Scholar
  • 6 Moroz LA, Gilmore NJ. A rapid sensitive l25I-fibrin solid phase fibrinolytic assay for plasmin. Blood 1975; 46: 543-553
    PubMedSearch in Google Scholar
  • 7 Moroz LA, Gilmore NJ. Fibrinolysis in normal plasma and blood. Evidence for significant mechanisms independent of the plasminogenplasmin system Blood 1976; 48: 431-445
    PubMedSearch in Google Scholar
  • 8 Edson JR, Vogt JM, Hasegawa DK. Abnormal prothrombin crossed-immuno-electrophoresis in patients with lupus inhibitors. Blood 1984; 64: 807-816
    PubMedSearch in Google Scholar
  • 9 Egeblad K. Effects of epsilon-aminocaproic acid on fibrin clot lysis. Thromb Diathes Haemorrh 1966; 15: 173-191
    PubMedSearch in Google Scholar
  • 10 Thorsen S. Influence of fibrin on the effect of 6-aminohexanoic acid on fibrinolysis caused by tissue plasminogen activator or urokinase. In Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JE, Rowan RM, Samama MM, Desnoyers PC. (eds) Raven Press; New York: 1978. 3 269-283
    Search in Google Scholar
  • 11 Thorsen S. Differences in the binding to fibrin of native plasminogen and plasminogen modified by proteolytic degradation. Influence of omega-amino carboxylic acids Biochim Biophys Acta 1975; 393: 55-63
    CrossrefPubMedSearch in Google Scholar
  • 12 Morris JR, Castellino FJ. The role of the lysine binding sites of human plasmin in the hydrolysis of human fibrinogen. Biochim Biophys Acta 1983; 744: 99-104
    CrossrefPubMedSearch in Google Scholar
  • 13 Okamoto S, Oshiba S, Mihara H, Okamoto U. Synthetic inhibitors of fibrinolysis: In vitro and in vivo mode of action. Ann NY Acad Sci 1968; 146: 414-429
    CrossrefPubMedSearch in Google Scholar
  • 14 Westlund LE, Lunden R, Wallen P. Effect of EACA, PAMBA, AMCA and AMBOCA on fibrinolysis induced by Streptokinase, Urokinase and tissue activator. Haemostasis 1982; 11: 235-241
    PubMedSearch in Google Scholar
  • 15 Petersen LC, Brender J, Svenson E. Zymogen-activation kinetics. Biochem J 1985; 225: 149-158
    CrossrefPubMedSearch in Google Scholar