Aprotinin inhibits thrombin formation and monocyte tissue factor in simulated cardiopulmonary bypass.
BACKGROUND
Aprotinin reduces perioperative bleeding after open heart surgery, primarily by inhibiting fibrinolysis. In addition, the drug has both procoagulant and anticoagulant effects that involve complex reactions of coagulation proteins and cells that are incompletely understood. This study tests the hypothesis that aprotinin has an anticoagulant effect on the extrinsic coagulation pathway.


METHODS
Human heparinized blood was recirculated through a membrane oxygenator with and without high concentrations of aprotinin (18.4 microM). Serial plasma samples were obtained at intervals up to 240 minutes.


RESULTS
Aprotinin significantly reduced the progressive increase in prothrombin fragments (F1.2) and thrombin-antithrombin complex beginning immediately. Aprotinin also significantly reduced monocyte expression of tissue factor and Mac-1. Aprotinin did not significantly reduce factor VII or factor VIIa.


CONCLUSIONS
During simulated cardiopulmonary bypass, aprotinin immediately inhibits kallikrein and thrombin formation via the intrinsic coagulation pathway. Later, aprotinin inhibits monocyte expression of tissue factor and the extrinsic coagulation pathway. The ability of aprotinin to inhibit monocyte tissue factor provides a means to reduce thrombin formation in blood aspirated from the wound during open heart surgery.
Khan
M M
MM
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Gikakis
N
N
Miyamoto
S
S
Rao
A K
AK
Cooper
S L
SL
Edmunds
L H
LH
Colman
R W
RW
D000990:Antithrombin III / Q000378:metabolism; D007611:Aprotinin / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass; D015942:Factor VIIa / Q000037:antagonists & inhibitors*; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008955:Models, Cardiovascular; D009000:Monocytes / Q000187:drug effects*; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*
D006490:Hemostatics; D016177:Macrophage-1 Antigen; D010446:Peptide Fragments; C046193:antithrombin III-protease complex; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D013925:Thromboplastin; D007611:Aprotinin; D010447:Peptide Hydrolases; D015942:Factor VIIa