Prostaglandin E2 potentiation of platelet aggregation induced by LASS endoperoxide: absent in storage pool disease, normal after aspirin ingestion.
Patients with storage pool disease and normal subjects who ingest aspirin show diminished collagen-induced platelet aggregation and an absent second wave of aggregation with ADP or adrenaline. These 'second-phase' aggregation responses are thought to be mediated by cyclic endoperoxide ('labile aggregation stimulating substance', LASS) that is derived from arachidonic acid and is the precursor of prostaglandin E2 (PGE2) and PGE2alpha. Furthermore, although PGE2 does not directly aggregate platelets, it markedly potentiates LASS-induced aggregation. The platelets of six patients with storage pool disease were capable of converting arachidonic acid to LASS, but the potentiation of LASS-induced aggregation by PGE2 was markedly diminished. In contrast, PGE2-potentiation of LASS aggregation was not reduced after aspirin ingestion. The effects of aspirin can be attributed entirely to its ability to block the enzymatic conversion of arachidonic acid to LASS and PGE2. These findings explain why a mutual correction of the aggregation defects is often seen when aspirin-treated platelets are mixed with storage pool-deficient platelets. This is because 'aspirin platelets' aggregate to the mixture of LASS and PGE2 produced by the storage pool-deficient platelets, which are themselves unresponsive. The findings in storage pool disease support previous conclusions that prostaglandin sensitization of platelets to the pro-aggregatory effects of LASS is an important factor in irreversible aggregation, and could be clinically important.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D001791:Blood Platelet Disorders / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D010545:Peroxides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011458:Prostaglandins E / Q000096:biosynthesis / Q000494:pharmacology*
D001095:Arachidonic Acids; D010545:Peroxides; D011458:Prostaglandins E; D000244:Adenosine Diphosphate; D001241:Aspirin