Cardiopulmonary support and physiology
Pump-induced platelet aggregation with subsequent hypotension: Its mechanism and prevention with clopidogrel

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Objectives

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.

Methods and 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.

Conclusion

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.

CTSNet classification

25
33

Abbreviations and Acronyms

ADP
adenosine diphosphate
CPB
cardiopulmonary bypass surgery
EDTA
ethylenediamine tetraacetic acid
5-HT
serotonin
NO
nitric oxide
SD
standard deviation
SEM
standard error of the mean
vWf
von Willebrand factor

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