Pump-induced platelet aggregation with subsequent hypotension: Its mechanism and prevention with clopidogrel.
OBJECTIVE
Use of extracorporeal circuits in cardiopulmonary bypass and hemodialysis often causes bleeding problems and hypotension. As shown previously, this might be caused by activation of blood platelets due to pumping. The present study investigates the mechanism of pump-induced platelet aggregation and its possible prevention.


RESULTS
Continuous measurement of platelet aggregation in an extracorporeal shunt from a carotid to a femoral artery in rats showed that aggregation during the first 10 minutes of pumping was not reduced by coating the tube with albumin or heparin nor by using dalteparin instead of unfractionated heparin as anticoagulant. Also, pump characteristics seemed unimportant because aggregation could already be elicited by single tube compression with one pump roller. It was calculated that during compression wall shear stress in the tube rises far beyond the values known to induce platelet aggregation, occurring also in clinically used roller pumps. A crucial role for adenosine diphosphate was demonstrated by blockade of platelet adenosine diphosphate-P2Y12 receptors with the clinically used drug clopidogrel (50 mg/kg intravenously, n = 8). This prevented platelet aggregation and the fall of systemic blood pressure (to 71% +/- 12% in controls, n = 6) during 2 hours of continuous pumping.


CONCLUSIONS
We conclude that pump-induced platelet aggregation is not caused by factors released from the tube or its coating but is initiated by short bouts of high shear stress, and its continuation is critically dependent on adenosine diphosphate. The latter might have clinical relevance for patients connected to extracorporeal systems.
Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. p.borgdorff@vumc.nl
Piet
P
Borgdorff
Geert Jan
GJ
Tangelder
D000244:Adenosine Diphosphate / Q000502:physiology; D000418:Albumins / Q000494:pharmacology; D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D000077144:Clopidogrel; D020099:Coated Materials, Biocompatible; D006493:Heparin / Q000494:pharmacology; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology*; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000418:Albumins; D020099:Coated Materials, Biocompatible; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine