Human Platelet Activation In The Absence Of Aggregation: A Calcium-Dependent Phenomenon Independent Of Thromboxane Formation

In response to the ionophore A 23187, thrombasthenic platelets undergo a change in light transmission (LT) using either PRP or washed platelets. This change was accompanied by a normal release of ¹⁴C serotonin (5HT) and thromboxane (TX) synthesis in absence of aggregation; lactic dehydrogenase determinations showed no evidence of platelet lysis. Ultrastructural qualitative electron microscopy revealed the formation of the central gel mass and the central apposition of organelles but the platelets were loosely packed. This ultrastructural change which was accompanied by biochemical phenomena was quantified; this includes an increase of the elongation coefficient, a decrease of the circularity coefficient as well as a decrease of the percentage of granules and surface connecting system in comparison with the total volume of the cell.

The change in light transmission was not inhibited by non-steroidal anti-inflammatory drugs (aspirin, indometha- cin, flurbiprofen) suggesting a dissociation between a normal release of ¹⁴C-5HT and an absence of TX formation. Moreover it was not inhibited by creatine phosphate/ creatine phosphokinase, prostaglandin E₁ or cytochalasine and/or colchicine; it was then not dependent on ADP, cAMP or the integrity of microfilaments and microtubules. However chlorpromazine, TMB8 and dibucaine, drugs which interfere with intracellular membrane transport of calcium ions inhibited this platelet activation (change in LT, ¹⁴C-5HT release or TX synthesis).

The stimulation of internal calcium fluxes by the ionophore was sufficient to induce platelet activation in the absence of aggregation; it was found to be independent of TX formation.