Platelet activity and in vivo arterial thrombus formation in rats with mild hyperhomocysteinaemia.

Abstract

Elevated plasma levels of total homocysteine (hcy) have been associated with an increased occurrence of arterial thrombosis. In the present study, we investigated the influence of hyperhomocysteinaemia on platelet aggregation and arterial thrombus formation in vivo. Fifty-one rats were included in the study, of which 29 received hcy in the drinking water for 4 weeks. Blood samples were withdrawn for measurement of platelet count and mean platelet volume. Platelet aggregation response in platelet-rich plasma following adenosine diphosphate or collagen stimulation were examined. In vivo thrombus formation was investigated by transillumination and videotape recording of the rat femoral artery after a thrombogenic injury was established. Off-line videotape analysis using computer-assisted planimetry permitted quantification of the thrombus area, and area versus time curves were obtained. In the intervention group receiving hcy, total hcy in plasma increased two-fold to 14.3 micromol/l, as compared with 7.3 micromol/l in the control group (P < 0.001). The platelet count and mean platelet volume did not differ between the two groups. In vivo thrombus formation expressed as the area under the curve or maximum thrombus area was not found to be altered in the presence of an increased homocysteine level, neither was adenosine diphosphate-induced platelet aggregation. However, collagen-induced platelet aggregation significantly decreased in the hcy group (P = 0.02). Pro-thrombotic effects of isolated mild hyperhomocysteinaemia are not supported by the present study in rats.