Heterogeneity of fibrinogen receptor expression on platelets activated in normal plasma with ADP: analysis by flow cytometry

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Abstract
Summary. Fibrinogen receptor expression of platelets activated in normal plasma by ADP was measured by flow cytometry after labelling bound fibrinogen with fluorescein-conjugated antifibrinogen antibody. The platelet response to ADP was heterogeneous both with respect to number of platelets binding fibrinogen and the amount of fibrinogen bound per platelet. The proportion of platelets showing positive antifibrinogen antibody binding increased with increasing ADP concentration; however, even at 10−3m ADP, usually about one-fifth of the platelets failed to demonstrate bound fibrinogen. The non-responsive platelets tended to be the smaller ones. The relative fluorescence intensity of individual platelets also increased as ADP concentration was increased, indicating that the average number of fibrinogen molecules bound was also related to agonist concentration. The amount of fibrinogen bound following platelet activation directly correlated with the quantity of surface glycoprotein IIb detected by Tab antibody and with platelet size. This study demonstrates that platelet response to ADP in native plasma is heterogeneous in both the proportion of platelets activated and in the number of available fibrinogen receptors per platelet. This heterogeneity is related to platelet size and glycoprotein IIb-IIIa content. These observations indicate that models of ligand interaction with membrane receptors on intact cells requiring an exposure step must take into account the heterogeneity of response within a cell population. In addition to providing new insights into the response of individual platelets to activation, these results suggest that study of platelet bound fibrinogen by flow cytometry may be useful for the detection of platelet activation in vivo.