Protection of platelets during long-term extracorporeal membrane oxygenation in sheep with a single dose of a disintegrin.
BACKGROUND
Both short- and long-term extracorporeal membrane oxygenation (ECMO) causes platelet loss and dysfunction. Bitistatin is a reversible inhibitor of the platelet glycoprotein IIb/IIIa receptor. This study tests the hypothesis that inhibition of platelets by bitistatin during initial contact with the perfusion circuit preserves platelet number and function during long-term ECMO in sheep.


RESULTS
Bitistatin, purified from crude snake venom, was tested for its effect on platelet count, responsiveness to ADP, release of platelet factor 4, and prevention of surface-adsorbed glycoprotein IIIa in vitro and during 24 hours of ECMO in nine splenectomized sheep. During simulated extracorporeal circulation, 0.5-1.0 microgram/ml bitistatin significantly prevented platelet adhesion, attenuated release of sheep platelet factor 4, and preserved platelet responsiveness to ADP. During ECMO at 1.8 l/min for 24 hours, a single dose of bitistatin (200 micrograms/kg) (n = 4) produced higher platelet counts (p = 0.0002) and suppressed release of platelet factor 4 (p = 0.035) for 16 hours compared with five control animals. This dose of bitistatin caused an immediate inhibition of platelet aggregation; however, between 4 and 24 hours of perfusion, platelets of bitistatin-treated animals were more responsive to ADP (p < 0.0001) compared with platelets in control animals. The amount of glycoprotein IIIa antigen extracted by Triton X-100 from the perfusion circuits was reduced in bitistatin-treated sheep.


CONCLUSIONS
A single dose of bitistatin given before blood contact with the ECMO circuit briefly inhibits platelet adhesion and aggregation but thereafter preserves platelet numbers and function and suppresses alpha-granule release for 12-16 hours of ECMO.
Shigeta
O
O
Division of Cardiothoracic Surgery, School of Medicine, University of Pennsylvania, Philadelphia 19104.
Gluszko
P
P
Downing
S W
SW
Lu
W
W
Niewiarowski
S
S
Edmunds
L H
LH
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects*; D015199:Extracorporeal Membrane Oxygenation; D010455:Peptides / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010976:Platelet Count / Q000187:drug effects; D010978:Platelet Factor 4 / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D012756:Sheep; D012910:Snake Venoms; D013997:Time Factors; D014757:Viper Venoms / Q000627:therapeutic use*
D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D012910:Snake Venoms; D014757:Viper Venoms; C062186:bitistatin; D010978:Platelet Factor 4; D000244:Adenosine Diphosphate