Platelet shape change in whole blood: differential effects of endotoxin

The effect of endotoxic lipopolysaccharide (LPS) on platelet shape change (PSC; a preaggregation event) was investigated. PSC is accompanied by an increase in median platelet volume (MPV), which was measured using a channelyzer. In whole blood, but not in platelet rich plasma (PRP), LPS (final concentration 80 mg/l) caused an increase in MPV that could be detected for 2 h. When PRP (prepared from LPS- and saline-pretreated whole blood) was incubated for 40 min, the LPS-mediated increase in MPV could no longer be detected. Taken together, these data imply that PSC is both initiated and maintained by a labile factor(s) present in whole blood, but not in PRP. PRP was prepared from LPS-pretreated whole blood and incubated for 40 min to allow reversal of the LPS-induced PSC; further stimulation with LPS caused PSC. Platelets from LPS-pretreated whole blood also showed enhanced PSC with serotonin (5-HT), diminished PSC with platelet activating factor (PAF), and no change of response to ADP and collagen. Hence, LPS pretreatment of whole blood differentially alters responses of platelets to further stimulation with LPS and other agonists. A specific PAF antagonist completely abolished the effect of LPS on MPV. These data may contribute to an understanding of the cascading thrombotic events and thrombocytopenia associated with septicaemia.