Thromboxane A 2 Causes Feedback Amplification Involving Extensive Thromboxane

Close platelet-to-platelet contact induced by weak agonists in a medium with a low concentration of Ca2 leads to thromboxane A2 (TXA2) formation, release of granule contents. and secondary aggregation. These responses do not occur in a medium containing Ca2 in the physiological range (1 to 2 mmol/L). Experiments were done to determine whether feedback amplification is required to generate amounts of TXA2 that are sufficient to cause secondary aggregation and the reactions associated with it, or whether close platelet-to-platelet contact alone is sufficient to generate enough TXA2 to produce these responses. Platelets were washed and resuspended in a modified Tyrode solution to which no calcium salt was added that contained 0.35% albumin and apyrase. This medium contains 20 ,smol/L Ca2 and 1 mmol/L Mg2 . Platelets were aggregated with adenosine diphosphate (ADP) in the presence of fibrinogen. agglutinated with polylysine, or after pretreatment with chymotrypsin. aggregated with fibrinogen. In the low-Ca2 medium. all these agonists caused platelets to adhere to each other, followed by secondary aggregation with TXA2 formation