Thrombasthenia: A Model for Studying Platelet Activation in the Absence of Aggregation

In response to the ionophore A 23 187, thrombasthenic platelets undergo normal shape charge, serotonin release and metabolism of ¹⁴C-arachidonic acid (including liberation from prelabelled platelet phospholipids and conversion to thromboxane B₂ and HETE). These responses, using either PRP or washed platelets, are accompanied by a characteristic optical density (OD) change in the absence of aggregation. This change was associated with the formation of a central contractile gel mass and central apposition of organelles, but lactic dehydrogenase determinations showed no evidence of platelet lysis. These reisuits can be mimicked by stirring A 23 187 with normal platelets in the presence of EOTA or EGTA. The OD change in this system was inhibited by chlorpromazine, propranolol and other drugs which interfere with membrane transport of Ca²⁺ but not by colchicine, cyto-, chalasin B, prostaglandin Ej, creatine phosphate/creatine Phosphokinase or antimycin and deoxyglucose.

These findings show that the action of ionophore on thrombasthenic platelets provides a model for dissociating platelet thromboxane formation, contraction and secretion, all of which are dependent on intracellular calcium shifts, from aggregation, for which extracellular calcium is required; they suggest that the underlying membrane glycoprotein abnormality in thrombasthenia may result in a failure to react with extracellular calcium.