A human model of platelet–leucocyte adhesive interactions during controlled ischaemia in patients with peripheral vascular disease

Abstract

Aims: In humans, little is known about the effects of platelet–leucocyte interactions on blood viscosity and microvascular perfusion. This study tested the hypotheses that (1) activation and interactions between platelets and leucocytes may have an impact on microvascular blood viscosity and perfusion in patients with stage II peripheral arterial occlusive disease, and (2) a powerful antiplatelet drug such as Clopidogrel might help to improve microvascular perfusion by reducing platelet–leucocyte activation and blood viscosity.

Methods: Plasma concentrations of certain markers of leucocyte and platelet activation, in addition to low and high shear rate blood viscosity, were measured before and after a repeated exercise treadmill test. Functional parameters including maximum walking time, transcutaneous oxygen pressure, and half recovery time were also measured.

Results: Blocking platelet activation only with a single dose of Clopidogrel (300 mg) did not improve microvascular blood viscosity and perfusion after repeated exercise, but a significant improvement in microvascular perfusion during controlled ischaemia and a lack of post exercise increase in low shear rate blood viscosity was achieved when both platelet and leucocyte activation were suppressed by a relatively longer treatment with Clopidogrel (four days).

Conclusions: Clopidogrel, by inhibiting platelet activation and aggregation, might also block the vicious cycle of leucocyte–platelet activation, thus improving the functioning of the microcirculation.