Summary
Aspirin is the most commonly used antithrombotic drug in primary and secondary prophylaxis
against cardio- and cerebrovascular disease. In previous studies from our laboratory
it was demonstrated that the effect of aspirin on collagen-induced thrombus formation
in a parallelplate perfusion device with laminar blood flow is shear rate dependent.
Although aspirin did not affect collagen-induced thrombus formation at 650 s-1 (medium sized arteries), a significant inhibition of thrombus formation by approximately
38% at 2,600 s-1 (moderately stenoses in medium sized arteries) was observed. At present we have extended
these studies to thrombus formation at the apex of eccentric stenoses in a parallel-plate
perfusion chamber device. The stenoses reduced the cross-sectional area of the blood
flow channel of the perfusion chambers by 60 or 80%, introducing disturbed laminar
flow and apex wall shear rates of 2,600 and 10,500 s-1, respectively. The corresponding wall shear stresses were 80 and 315 dynes/cm2, respectively.
Aspirin reduced the platelet thrombus volume at the 60% stenosis by 45% (p <0.03),
and the fibrin deposition by 70% (p <0.004). However, none of these parameters were
affected by aspirin at the 80% stenosis. These observations may at least partly explain
why aspirin has a limited clinical effect in preventing arterial thrombus formation
in atherosclerotic vessels at high shear and disturbed blood flow. In contrast, thrombus
formation in blood from one patient with Glanzmann’s thrombasthenia and two patients
with von Willebrand disease subtype 2M was almost abolished at this blood flow condition.
Thus, blocking the function of either von Willebrand factor or glycoprotein IIb/IIIa
may represent better antithrombotic approaches for such critical events than blocking
the prostaglandin metabolism by aspirin. The lack of effect of aspirin on thrombus
formation at the 80% stenosis may reflect shear-induced platelet activation at the
stenosis inlet region, since shear-induced platelet aggregation in rotational viscometers
is not affected by aspirin at shear stresses exceeding 100 dynes/cm2.
