The effective concentration of epsilon-aminocaproic Acid for inhibition of fibrinolysis in neonatal plasma in vitro.
BACKGROUND
Pediatric patients, particularly neonates, are at high risk for bleeding complications after cardiovascular surgery because of their immature hemostatic system, small size, and the complex operations they require. Activation of intravascular fibrinolysis is one of the principle effects of cardiopulmonary bypass that causes poor postoperative hemostasis. This complication has long been recognized and treated with antifibrinolytic medications, including the lysine analog epsilon aminocaproic acid (EACA). The therapeutic plasma concentration of EACA has been scientifically determined for the adult population, but the current recommended dosage for neonates has been empirically derived from adult studies. Therefore, we investigated the appropriate concentration of EACA for neonates undergoing bypass.


METHODS
We conducted an in vitro study using neonatal plasma derived from the placenta/cord units from 20 term, elective cesarean deliveries. Graded concentrations of EACA were added to aliquots of the plasma pool before activating fibrinolysis with tissue-type plasminogen activator. Standard kaolin-activated thromboelastograms were then run with the primary outcome variable being estimated percent lysis. These procedures were repeated on samples of commercially available pooled adult normal plasma for comparison.


RESULTS
We found that neonatal plasma required significantly lower concentrations of EACA to completely prevent fibrinolysis than did adult plasma (44.2 microg/mL and 47.8 microg/mL for neonatal plasma and 94.4 and 131.4 microg/mL in adult plasma for 400 and 1000 U/mL of plasminogen activator, respectively, P < 0.001).


CONCLUSIONS
Our data establish the minimal effective concentration of EACA necessary to completely prevent fibrinolysis in neonatal blood in vitro. This concentration is significantly less than that targeted by current dosing schemes, indicating that neonates are possibly being exposed to greater levels of EACA than is clinically necessary.
Yurka
Heather G
HG
Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Wissler
Richard N
RN
Zanghi
Christine N
CN
Liu
Xiang
X
Tu
Xin
X
Eaton
Michael P
MP
D000328:Adult; D000375:Aging / Q000097:blood; D015119:Aminocaproic Acid / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D002585:Cesarean Section; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008826:Microbial Sensitivity Tests; D010949:Plasma / Q000187:drug effects*; D010960:Plasminogen Activators / Q000494:pharmacology; D013916:Thrombelastography; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D000933:Antifibrinolytic Agents; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D015119:Aminocaproic Acid