Effects of antifibrinolytic agents on the life span of fibrin sealant.
Fibrin sealant, a biologic glue consisting of fibrinogen and thrombin, has been used in a variety of surgical procedures. The usefulness of fibrin sealant may be prolonged by the addition of antifibrinolytic agents. This study compared the efficacy of transexamic acid (30 mg/ml), epsilon-aminocaproic acid (25 mg/ml), and aprotinin (3000 KIU/ml) to provide data on the choice of an appropriate antifibrinolytic agent for use with fibrin sealant. By use of a modified in vitro plasma euglobulin lysis time (hours), all agents were found to be superior (n = 10 for each agent, P < 0.05, analysis of variance for completely randomized design followed by Dunnett's test for multiple comparisons) to control. Lysis times (mean +/- SE) were (control) 50.9 +/- 0.5, (tranexamic acid) 402.6 +/- 25.4, (epsilon-aminocaproic acid) 433.5 +/- 21.2, and (aprotinin) 393.9 +/- 26.0. Using the in vivo implantation of fibrin sealant supplemented with 125I-fibrinogen in the rat peritoneum significant improvement in percentage clot (mean +/- SE) remaining was found (P < 0.05, analysis for repeated measures followed by tests for multiple comparisons) under the following conditions: at 3 hr by weight (n = 15), tranexamic acid (70.13 +/- 2.02%) was superior to aprotinin (61.22 +/- 2.21%) and control (61.28 +/- 2.36%); at 3 hr by radioactivity counts (n = 19), tranexamic acid (76.29 +/- 0.75%) was superior to epsilon-aminocaproic acid (72.52 +/- 1.28%) and aprotinin (73.84 +/- 0.78%); at 72 hr by radioactivity counts (n = 10), aprotinin (27.30 +/- 2.45%) was superior to epsilon-aminocaproic acid 19.76 +/- 3.09% and control (20.38 +/- 3.01%). These data suggest the early (3-hr) superiority of tranexamic acid as an inhibitor of plasminogen activation and the late (72-hr) effectiveness of aprotinin as an inhibitor of plasmin. The possibility of a synergistic effect of tranexamic acid and aprotinin is suggested.
Pipan
C M
CM
Department of Surgery, University of Virginia Health Sciences Center, Charlottesville 22908.
Glasheen
W P
WP
Matthew
T L
TL
Gonias
S L
SL
Hwang
L J
LJ
Jane
J A
JA
Spotnitz
W D
WD
D000269:Adhesives; D015119:Aminocaproic Acid / Q000494:pharmacology; D000818:Animals; D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D007611:Aprotinin / Q000494:pharmacology; D001777:Blood Coagulation; D004355:Drug Stability; D005340:Fibrinogen; D005342:Fibrinolysis; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012712:Serum Globulins / Q000378:metabolism; D013917:Thrombin; D013997:Time Factors; D014148:Tranexamic Acid / Q000494:pharmacology
D000269:Adhesives; D000933:Antifibrinolytic Agents; D012712:Serum Globulins; D014148:Tranexamic Acid; D005340:Fibrinogen; D007611:Aprotinin; D013917:Thrombin; D015119:Aminocaproic Acid