We assessed the integrity of the
prostaglandin synthetic pathway by measuring
malondialdehyde (MDA) production and studied platelet aggregation responses to
arachidonic acid and
PGG2 in 12 patients with
storage pool deficiency (SPD). Eight patients were deficient only in dense granules (delta-SPD) and four were deficient in both dense and alpha-granules (alpha delta-SPD). Production of MDA in response to
arachidonic acid (AA),
epinephrine, and
collagen suggested that the transformation of AA to
prostaglandin metabolites was normal in delta-SPD but abnormal in alpha delta-SPD and that the liberation of AA from
phospholipids were abnormal in the majority of patients with SPD. Since the content of secretable
adenosine diphosphate (
ADP) is diminished in SPD platelets, the aggregation responses of these platelets to AA and
PGG2 were studied to help answer the question whether these agents aggregate platelets directly or through release of endogenous
ADP. Among patients with delta-SPD, aggregation by both AA and
PGG2 was decreased in four albinos whose platelets were markedly deficient in
ADP. In contrast, normal, or less strikingly abnormal, responses were observed in patients whose platelets either contained higher levels of platelet
ADP or showed increased sensitivity to
ADP. The more marked impaired responses to AA and
PGG2 in patients with alpha delta-SPD suggest that substances derived from alpha-granules may also play a role in platelet aggregation by these agents. The aggregation responses in these patients with various types of SPD is consistent with a theory that granule-derived
ADP mediates platelet aggregation by AA and
PGG2.