Effect of combined COX-1 and COX-2 inhibition on platelet aggregation in-vivo

Since the pain-killer VIOXX was withdrawn from the market, september 2004,
because of serious side-effects in heart patients, the mechanism of these side
effects is still not clear (Wadman M - Nature 2006;441:262). A dominant
hypothesis is that VIOXX and other selective COX-2 inhibitors are prothrombotic
by suppressing the formation of endothelial prostaglandin which is a well-known
inhibitor of platelet aggregation in-vitro, without interfering with COX-1
mediated formation of thromboxane which is a reinforcer of platelet
aggregation. As a consequence, the possible prothrombotic effect of selective
COX-2 inhibitors is expected to be neutralized by contamporary use of COX-1
inhibition with low-dose aspirin. The role of circulating prostacyclin and of
thromboxane in the possible enhancement of aggregation by selective COX-2
inhibitors has, however, never been demonstrated.

To investigate whether COX-2 inhibition enhances platelet aggregation by
suppression of prostacyclin formation without suppressing thromboxane formation

Platelet aggregation to increasing doses of adenosine diphosphate (ADP) and
epinephrine is studied in blood flowing from an antecubital vein into an
optometric device that continuously measures platelet aggregation within some
seconds after the blood left the venous canula. The measurements are performed
before and after intake of 500 mg aspirin.
For comparison, platelet aggregability is also tested in the conventional way,
with aid of a whole blood aggregometer

Canulation of an antecubital vein. Intake of aspirin

Burden: the experiment takes the subject about 2 hours of his time
Risk: negligible