Abnormalities of cytoplasmic Ca2+ in platelets from patients with uremia
JA Ware, BA Clark, M Smith and EW Salzman
Department of Medicine, Beth Israel Hospital, Boston, MA 02215.
Uremic patients have a hemorrhagic tendency, often associated with
prolonged bleeding times and decreased platelet function in vitro. Whether
these defects result from abnormalities in plasma factors affecting
platelet activity, platelet surface receptors, intracellular platelet
mediators, or other aspects of platelet behavior is unknown. To examine the
possibility that the abnormality in platelet function may result from
aberrations in Ca2+ homeostasis, blood was obtained from 29 patients with
severe uremia. The platelets were washed, loaded with the Ca2+ -sensitive
probes indo-1 and aequorin, gel-filtered, and resuspended in either plasma
or buffer. Of the 29 patients, seven had template bleeding times prolonged
to 11 minutes or more, but platelet aggregation in plasma was not
consistently impaired in these patients. However, in aequorin-loaded
platelets from the patients with long bleeding times, the highest elevation
of cytoplasmic calcium [( Ca2+]i) in response to the Ca2+ ionophore A23187,
arachidonate, adenosine diphosphate (ADP), or epinephrine was lower than
that seen in platelets from both uremic patients with less prolonged
bleeding times and normal volunteers. The reduced [Ca2+]i response was
associated with decreased aggregation of gel-filtered platelets suspended
in buffer. Suspending washed aequorin-loaded uremic platelets in normal
plasma for 20 minutes did not reverse the decreased agonist-induced rise in
[Ca2+]i; platelets from a normal donor resuspended in uremic plasma
aggregated and produced a normal increase in [Ca2+]i in response to
agonists. We conclude that the platelet defect seen in some patients with
uremia is associated with a decreased rise in platelet [Ca2+]i after
stimulation and that this is a manifestation of an intrinsic platelet
defect.
Volume 73,
Issue 1,
pp. 172-176,
01/01/1989
Copyright © 1989 by The American Society of Hematology
