Abnormal aggregation accompanies abnormal platelet Ca2+ handling in arterial thrombosis.
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. Turbidimetric studies of aggregation of diluted platelet-rich plasma (PRP) at 135 microM Ca2+ showed increased rates of aggregation for patients relative to normal controls. For ADP-stimulated aggregation, increased maximal rates (Vmax) 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.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002751:Chlortetracycline / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010974:Platelet Aggregation / Q000187:drug effects; D013927:Thrombosis / Q000097:blood*; D013997:Time Factors
D000634:Aminoquinolines; D000001:Calcimycin; D000244:Adenosine Diphosphate; D003094:Collagen; C035739:Quin2; D002118:Calcium; D002751:Chlortetracycline