Abnormal Aggregation Accompanies Abnormal Platelet Ca²⁺ Handling in Arterial Thrombosis

Summary

The resting levels of cytoplasmic Ca²⁺ (measured by Quin 2 fluorescence) and dense tubular Ca²⁺ (measured by chlorotetracycline, CTC, fluorescence) are shown to be higher in platelets from patients with arterial thrombosis than from normal donors. Turbidmetric studies of aggregation of diluted platelet-rich plasma (PRP) at 135 μM Ca²⁺ showed increased rates of aggregation for patients relative to normal controls. For ADP-stimulated aggregation, increased maximal rates (V_max) and decreased doses for half-maximal rates were observed. With collagen-stimulated aggregation, patient samples showed only decreased ED₅₀ values relative to normal controls. The changes in these values are linearly correlated with the elevation of resting dense tubular Ca²⁺ level determined by the calcium-CTC test carried out at 2 mM external Ca²⁺. For ADP-stimulated aggregation this relationship can be mimicked by pre-incubating normal platelets with subcritical concentrations of the Ca²⁺ ionophore A23187.

These results suggest that elevated cytoplasmic and dense tubular Ca²⁺ in the “resting state” is a major factor in arterial thrombosis, rendering the platelet more sensitive to the stimulation by physiologic agents.

Keywords

Platelet - Arterial thrombosis - Platelet hyperactivation - Platelet aggregation - Ca²⁺ uptake and release - Dense tubules - Chlorotetracycline - Quin 2

• References

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