Abnormal aggregation accompanies abnormal platelet Ca2+ handling in arterial thrombosis

N. M. Shanbaky, Y. Ahn, W. Jy, W. Harrington, L. Fernandez, D. H. Haynes

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalThrombosis and Haemostasis
Volume57
Issue number1
DOIs
StatePublished - 1987

ASJC Scopus subject areas

  • Hematology

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