Effects of epsilon-aminocaproic acid and aprotinin on leukocyte-platelet adhesion in patients undergoing cardiac surgery.
BACKGROUND
The administration of aprotinin during cardiopulmonary bypass (CPB) is hypothesized to decrease activation of leukocytes and platelets and possibly reduce their adhesion. Although epsilon-aminocaproic acid (EACA) shares the ability of aprotinin to inhibit excessive plasmin activity after CPB, its effect on leukocyte and platelet activation and leukocyte-platelet (heterotypic) adhesion is largely unknown. This study was performed to determine the relative effectiveness of the antifibrinolytics, aprotinin and EACA, at reducing leukocyte and platelet activation and leukocyte-platelet conjugate formation in patients undergoing CPB.


METHODS
Thirty-six patients scheduled to undergo cardiac surgery with CPB were randomized in a double-blind fashion to receive EACA, aprotinin, or saline (placebo). Markers of plasmin activity (D-dimer concentrations), platelet activation (CD62P), leukocyte activation (CD11b), and leukocyte-platelet adhesion (monocyte- and neutrophil-platelet conjugates) were measured before, during, and after CPB.


RESULTS
Platelet CD62P (P-selectin), monocyte CD11b, and monocyte-platelet conjugates were all significantly increased (compared with baseline) in the saline group during and after CPB. Despite equivalent reductions in D-dimer formation in patients receiving EACA (P < 0.0001) and aprotinin (P < 0.0001), decreases in platelet CD62P and monocyte CD11b expression were incomplete (not significantly different from saline control). In contrast, peak monocyte-platelet conjugate formation was significantly reduced by both EACA (P = 0.026) and aprotinin (P = 0.039) immediately after CPB.


CONCLUSIONS
EACA seems to be as effective as aprotinin at reducing peak monocyte-platelet adhesion after CPB. Furthermore, inhibition of excessive plasmin activity seems to influence monocyte-platelet adhesion. The findings suggest that monocyte-platelet conjugate formation may be a useful marker of monocyte and platelet activation in this clinical setting.
Greilich
Philip E
PE
Department of Anesthesiology & Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8894, USA. philip.greilich@utsouthwestern.edu
Brouse
Chad F
CF
Rinder
Christine S
CS
Smith
Brian R
BR
Sandoval
Bernardo A
BA
Rinder
Henry M
HM
Eberhart
Robert C
RC
Jessen
Michael E
ME
D000368:Aged; D015119:Aminocaproic Acid / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D007611:Aprotinin / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010973:Platelet Adhesiveness / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D000933:Antifibrinolytic Agents; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin; D015119:Aminocaproic Acid