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Platelet secretion defect associated with impaired liberation of
arachidonic acid and normal myosin light chain phosphorylation
AK Rao, K Koike, J Willis, JL Daniel, C Beckett, B Hassel, HJ Day, JB Smith and H Holmsen
We describe four patients with impaired platelet aggregation and 14C-
serotonin secretion during stimulation with adenosine diphosphate (ADP),
epinephrine, collagen, and platelet-activating factor. The response to
arachidonic acid was normal in all patients with regard to aggregation and
in three of the four with regard to 14C-serotonin secretion. The total
platelet adenosine triphosphate (ATP) and ADP content and the ATP to ADP
ratio was normal in all patients, thereby excluding storage pool deficiency
as the cause of the secretion defect. Studies with 3H-arachidonic
acid-labeled platelets revealed that the thrombin-induced liberation of
arachidonic acid from membrane-bound phospholipids was impaired in these
patients. Further, platelet thromboxane B2 production, measured using a
radioimmunoassay, was diminished during stimulation with ADP and thrombin,
but was normal with arachidonic acid, indicating that the oxygenation of
arachidonic acid was normal and that the diminished thromboxane production
was due to a defect in the liberation of arachidonic acid. Release of
arachidonic acid is mediated by phospholipases that are Ca++ dependent. To
examine whether these patients may have a defect in making intracellular
Ca++ available, another Ca++-dependent process, myosin light chain
phosphorylation, was studied during thrombin stimulation. Platelets from
three of the patients were found to behave the same as normal ones,
suggesting that the deficiency in phospholipase activity may not be due to
impaired Ca++ mobilization. Our studies demonstrate a novel group of
patients with platelet secretion defects associated with impaired
liberation of arachidonic acid from phospholipids. These patients exemplify
a congenital defect, other than deficiencies of cyclooxygenase and
thromboxane synthetase, by which thromboxane production may be impaired in
platelets.
Volume 64,
Issue 4,
pp. 914-921,
10/01/1984
Copyright © 1984 by The American Society of Hematology
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