The mechanism of thrombogenicity in hyperhomocysteinemia remains controversial. The authors investigated the association between elevated plasma homocysteine levels, platelet function, and blood coagulation. Blood was collected from healthy subjects and patients with critical limb ischemia. Basal platelet counts and platelet aggregation as well as flow cytometry were performed to assess spontaneous- and agonist-induced platelet aggregation as well as P-selectin and Glycoprotein IIb/IIIa expression at different homocysteine concentrations. Thromboelastography was performed, and platelet shape change was assessed, using a channelyzer, by measuring median platelet volume. Lactate dehydrogenase was measured, to indirectly assess red blood cell membrane integrity, after homocysteine exposure. The study results suggest that platelet activation and hypercoagulability occur after exposure to homocysteine, especially in patients with critical limb ischemia. Homocysteine concentrations of approximately 50 µmol/L appear to be the level at which these changes occur in vitro, and this effect on platelets appears to be indirect.
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