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Impaired cytoplasmic ionized calcium mobilization in inherited platelet
secretion defects
AK Rao, MA Kowalska and J Disa
Thrombosis Research Center, Temple University School of Medicine,
Philadelphia, PA.
Defects in platelet cytoplasmic Ca++ mobilization have been postulated but
not well demonstrated in patients with inherited platelet secretion
defects. We describe studies in a 42-year-old white woman, referred for
evaluation of easy bruising, and her 23-year-old son. In both subjects,
aggregation and 14C-serotonin secretion responses in platelet-rich plasma
(PRP) to adenosine diphosphate (ADP), epinephrine, platelet activating
factor (PAF), arachidonic acid (AA), U46619, and ionophore A23187 were
markedly impaired. Platelet ADP and adenosine triphosphate (ATP), contents
and thromboxane synthesis induced by thrombin and AA were normal. In
quin2-loaded platelets, the basal intracellular Ca++ concentration,
[Ca++]i, was normal; however, peak [Ca++]i measured in the presence of 1
mmol/L external Ca++ was consistently diminished following activation with
ADP (25 mumol/L), PAF (20 mumol/L), collagen (5 micrograms/mL), U46619 (1
mumol/L), and thrombin (0.05 to 0.5 U/mL). In aequorin-loaded platelets,
the peak [Ca++]i studied following thrombin (0.05 and 0.5 U/mL) stimulation
was diminished. Myosin light chain phosphorylation following thrombin (0.05
to 0.5 U/mL) stimulation was comparable with that in the normal controls,
while with ADP (25 mumol/L) it was more strikingly impaired in the
propositus. We provide direct evidence that at least in some patients with
inherited platelet secretion defects, agonist-induced Ca++ mobilization is
impaired. This may be related to defects in phospholipase C activation.
These patients provide a unique opportunity to obtain new insights into
Ca++ mobilization in platelets.
Volume 74,
Issue 2,
pp. 664-672,
08/01/1989
Copyright © 1989 by The American Society of Hematology
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