Hypothermia-induced platelet aggregation: no effect of aprotinin (trasylol) but inhibition by eptifibatide (integrilin).
OBJECTIVE
The serine-protease inhibitor aprotinin protects platelet function during cardiopulmonary bypass. However, its safety and efficacy during deep hypothermic circulatory arrest (DHCA) is controversial, and aprotinin is suspected to cause thrombosis especially during hypothermia. The platelet GP IIb/IIIa inhibitor eptifibatide has been assumed to preserve platelet function during cardiopulmonary bypass without increasing bleeding complications. The aim of this study was to compare the effect of aprotinin and eptifibatide on platelet function under conditions of DHCA.


METHODS
Heparinized blood from healthy volunteers (n = 10) was incubated in stasis for 30 minutes at 18 degrees C to simulate DHCA and compared to samples incubated at 37 degrees C. The effect of eptifibatide (2.5 microg/ml) and aprotinin (300 KIU/ml) on platelets under these conditions was analyzed by flow cytometry. Platelet aggregates were identified using CD41-antibody binding and size. GPIIb/IIIa function was evaluated with the activation-specific antibody PAC-1 after stimulation with 10 microM ADP. Aggregate numbers and antibody mean-fluorescence are reported as mean +/- standard deviation.


RESULTS
Hypothermia induced a 2.5-fold increase of aggregates ( p < 0.001) and a 2.6-fold increase of GPIIb/IIIa activation ( p < 0.001). This effect was not influenced by aprotinin but almost completely inhibited by eptifibatide ( p < 0.001).


CONCLUSIONS
Aprotinin has no procoagulatory effect on platelet function during hypothermia but is not protective either. Eptifibatide inhibits hypothermia-induced platelet aggregation in vitro and may prevent aggregate sequestration in the microvasculature and consecutive ischemic organ damage in vivo.
Straub
A
A
Department of Thoracic, Cardiac and Vascular Surgery, University of Tübingen, Tübingen, Germany. anstraub@nexgo.de
Azevedo
R
R
Beierlein
W
W
Wendel
H P
HP
Scheule
A M
AM
Ziemer
G
G
D007611:Aprotinin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D001800:Blood Specimen Collection; D003080:Cold Temperature; D000077542:Eptifibatide; D005434:Flow Cytometry; D006801:Humans; D007035:Hypothermia / Q000097:blood; D066298:In Vitro Techniques; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*
D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D007611:Aprotinin; D000077542:Eptifibatide