PLATELET CALCIUM HOMEOSTASIS IS ABNORMAL IN PATIENTS WITH SEVERE ARTERIOSCLEROSIS

To evaluate platelet calcium homeostasis in a typical thrombosis-prone clinical condition, 14 patients with severe arteriosclerosis and 11 healthy control subjects were studied. Platelet intracellular free calcium concentration ([Ca2+](i)) was evaluated by means of the fluorescent probe fura 2 under resting conditions and after challenge with 0.05, 0.1, and 0.5 U/mL thrombin (final concentrations). Three different concentrations of extracellular ionized calcium ([Ca2+](e)) were used: 1 mmol/L, 1 mu mol/L, and <1 nmol/L. Resting platelet [Ca2+](i) was significantly higher (P<.001) in patients than in control subjects. After addition of 0.05 U/mL thrombin, the relative increase of [Ca2+](i) was lower in patients than in control subjects in each of the three [Ca2+](e) conditions (P=.05 at 1 mmol/L, P=.02 at 1 mu mol/L, and P=.04 at <1 nmol/L). After addition of 0.1 U/mL thrombin, the relative increase of [Ca2+](i) was lower in patients than in control subjects under two [Ca2+](e) conditions, 1 mu mol/L and <1 nmol/L (P=.04 and P=.03, respectively). With 0.5 U/mL thrombin, a trend toward lower values in patients than in control subjects was observed, reaching statistical significance (P=.03) only at <1 nmol/L [Ca2+](e). These results suggest that calcium homeostasis is abnormal in platelets from patients with severe arteriosclerosis and probably reflects a chronic activation.