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Prostaglandin E 2 Potentiation of Platelet Aggregation Induced by LASS Endoperoxide: Absent in Storage Pool Disease, Normal after Aspirin Ingestion
Author(s) -
Weiss Harvey J.,
Willis Anthony L.,
Kuhn Douglas,
Brand Harvey
Publication year - 1976
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1976.tb00929.x
Subject(s) - aspirin , platelet , chemistry , arachidonic acid , prostaglandin e , biochemistry , medicine , endocrinology , enzyme
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 E 2 (PGE 2 ) and PGF 2α . Furthermore, although PGE 2 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 PGE 2 was markedly diminished. In contrast, PGE 2 ‐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 PGE 2 . 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 PGE 2 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.