Enoxaparin suppresses thrombin formation and activity during cardiopulmonary bypass in baboons.
OBJECTIVE
This study tests the hypotheses that enoxaparin, a low molecular weight heparin and potent inhibitor of factor Xa, alone or in combination with standard heparin, inhibits thrombin formation and activity and modulates complement activation and neutrophil elastase release during cardiopulmonary bypass in baboons.


METHODS
After preliminary studies to determine doses and possible species differences to anticoagulants and protamine, 27 anesthesized baboons had normothermic cardiopulmonary bypass with standard, unfractionated, porcine intestinal heparin, enoxaparin, or a combination of heparin and enoxaparin. Protamine in appropriate doses was used to reverse anticoagulation. Blood samples were obtained at 6 time points. Activated clotting times were monitored; template bleeding times were measured before and up to 24 hours after cardiopulmonary bypass.


RESULTS
Hemodynamic measurements were not affected by the anticoagulant. Activated clotting times remained above 400 seconds throughout bypass, and no clots were observed. The anticoagulant did not alter platelet count, aggregation to adenosine diphosphate, release of beta-thromboglobulin, release of neutrophil elastase, or complement C3b/c and C4b/c. Enoxaparin alone, but not in combination, significantly reduced plasma levels of prothrombin fragment F1.2, fibrinopeptide A, and thrombin-antithrombin complexes but prolonged template bleeding times for more than 24 hours.


CONCLUSIONS
Enoxaparin significantly reduces thrombin formation and activity during cardiopulmonary bypass but does not suppress complement activation and neutrophil elastase release and is not adequately reversed by protamine after bypass.
Gikakis
N
N
Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, PA, USA.
Rao
A K
AK
Miyamoto
S
S
Gorman
J H
JH
Khan
M M
MM
Anderson
H L
HL
Hack
C E
CE
Sun
L
L
Niewiarowski
S
S
Colman
R W
RW
Edmunds
L H
LH
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D001760:Bleeding Time; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003167:Complement Activation / Q000187:drug effects; D017984:Enoxaparin / Q000627:therapeutic use*; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000627:therapeutic use; D019272:Leukocyte Elastase / Q000187:drug effects; D010215:Papio; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D006493:Heparin; D019272:Leukocyte Elastase; D013917:Thrombin; D015951:Factor Xa