Inhibition of Fibrinolysis in the Burned-Infected Rat: Antiplasmin Induced by Burn Wound Infection[*]
20 March 1975
Accepted 04 January 1976
03 July 2018 (online)
Infection is the leading cause of death in the burned patient. To study the effects of uncomplicated and lethally-infected burn wounds on certain hematologic indices, a dorsal scald burn was administered to 250 rats. One group was then infected with Pseudomonas aeruginosa. These rats expired within 10 days. A burned, uninfected, group survived. Sequential determinations were made of fibrinogen, fibrinolysis, antiplasmins, plasminogen antiactivators, cultures, and autopsy findings.
Fibrinogen concentrations were higher in the infected animals within 2 days postbum and at day 3 (p <0.05). Plasminogen levels fell precipitously 3 days postburn in the burned-infected group. Acid neutralization of antiplasmins was not entirely effective. Serum from infected animals markedly prolonged the lysis time of clots in a standard test system, lowered plasmin activity in the caseinolytic assay, and transiently prolonged the euglobulin lysis time.
The cause of these findings remains unknown. The marked fall in plasminogen in the infected animals may be entirely due to unneutralized antiplasmin activity and was coincident with a decline in fibrin-related antigens. These antiplasmins may exert deleterious effects on microcirculatory dynamics and were closely linked to the animals’ demise.
* The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Defense.
- 1 Andes W.a. 1974. Acute hematologic changes in the severely burned patient. Abstract and Presentation, Program. American Burn Association; Dallas, Texas.:
- 2 Aoki N, von Kaulla K. N. 1969; Inactivation of human serum plasminogen and antiactivator by synthetic fibrinolysis inducers. Thrombosis et Diathesis Haemorrhagica 22: 251.
- 3 Bergstein J. M, Michael A. F. 1973; Renal cortical fibrinolytic activity in the rabbit following one or two doses of endotoxin. Thrombosis et Diathesis Haemorrhagica 29: 27.
- 4 Bocci V, Pacini A. 1973; Factors regulating plasma protein synthesis II. Influence of fi-brinogenolytic products on plasma fibrinogen concentration. Thrombosis et Diathesis Haemorrhagica 29: 63.
- 5 Brodsky I, Lewis H. D. 1966; Evaluation of fibrinolysis in hepatic cirrhosis, relation of serial thrombin time and euglobulin lysis time. American Journal of Clinical Pathology 45: 61.
- 6 Campbell D. A, Gabriel L. T, van Hoek D. W. 1950; A study of the clotting mechanism in thermal burns. Surgical Forum II 515.
- 7 Curreri P. W, Lindberg R. B, Divincenti F. C, Pruitt Jr. B. A. 1970; Intravenous administration of carbenicillin for septicemia due to Pseudomonas aeruginosa following thermal injury. Journal of Infectious Disease 122 Supplement, 540.
- 8 Canrot K. 1973; Rat α2-acute phase globulin, a human α1 macroglobulin homologue: Interaction with plasmin and trypsin. Biochimica et Biophysica Acta 322: 61.
- 9 Horne C. H. W, Forbes C. D, Prentice C. R. M. 1973; Antiplasmin activity of rat serum slow α-globulins. British Journal of Haematology 24: 115.
- 10 Kropatkin M. L, Izak G. 1968; Studies of the hypercoagulable state: the regulation of fibrinogen production in experimental hyper- and hypo-fibrinogenemia. Thrombosis et Diathesis Haemorrhagica 19: 547.
- 11 Leavelle D. E, Mertens B. F, Bowie E. J. W, Owens C. A. 1971; Staphylococcal clumping on microtiter plates: A rapid, simple method for measuring fibrinogen split products. American Journal of Clinical Pathology 55: 452.
- 12 Lipinski B, Lybulska J, Worowski K, Jeljaszewicz J. 1969; Blood clotting and fibrinolysis in experimental staphylococcal infection. Pathologia et Microbiologia 34: 295.
- 13 Margaretten W, Zunker H. E, Mckay D. G. 1964; Production of the generalized Schwartzman reaction in pregnant rats by intravenous infusion of thrombin. Laboratory Investigation 13: 552.
- 14 Merskey C. 1973; Editorial: Defibrination syndrome or. Blood 41: 599.
- 15 Meyers A. 1972; Fibrin split products in the severely burned patient. Archives of Surgery 105: 404.
- 16 Perfentjev I. A, Johnson M, Clifton E. E. 1953; The determination of plasma fibrinogen by turbidity with ammonium sulfate. Archives of Biochemistry and Biophysics 47: 470.
- 17 Remmert L. F, Cohen P. 1949; Partial purification and properties of a proteolytic enzyme of human serum. journal of Biological Chemistry 181: 431.
- 18 Schoendorf T. H, Rosenberg M, Beller F. K. 1971; Endotoxininduced disseminated intravascular coagulation in nonpregnant rats. American Journal of Pathology 65: 51.
- 19 Sherry S, Lindemeyer R.L, Fletcher A. P, Alkjaersig N. 1959; Studies on enhanced fibrinolytic activity in man. Journal of Clinical Investigation 38: 810.
- 20 Sherry S, Fletcher A. P, Alkjaersig N. 1959; Fibrinolysis and fibrinolytic activity in man. Physiological Reviews 39: 343.
- 21 Teplitz C. 1965; Pathogenesis of Pseudomonas vasculitis and septic lesions. Archives of Pathology 80: 297.
- 22 van Kaulla K. N, Schultz R. L. 1958; Methods for the evaluation of human fibrinolysis: Studies with two combined techniques. American Jorunal of Clinical Pathology 29: 104.
- 23 Walker H. L, Mason A. D. 1968; A standard animal burn. Journal of Trauma 8: 1049.
- 24 Weimer H. E, Benjamin D. C. 1965; Immunochemical detection of an acute-phase protein in rat serum. American Journal of Physiology 209: 736.
- 25 Wolf P. 1968; Fibrinolytic activity and coronary artery disease. Lancet 1: 1312.
- 26 Yegge J. 1970; Changes in blood coagulation and fibrinolysis during the postoperative period. American Journal of Surgery 119: 225.