Abnormalities of cytoplasmic Ca2+ in platelets from patients with uremia.
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.
Ware
J A
JA
Department of Medicine, Beth Israel Hospital, Boston, MA 02215.
Clark
B A
BA
Smith
M
M
Salzman
E W
EW
D000331:Aequorin; D000368:Aged; D001760:Bleeding Time; D001791:Blood Platelet Disorders / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D007211:Indoles; D008163:Luminescent Measurements; D008875:Middle Aged; D010974:Platelet Aggregation; D014511:Uremia / Q000097:blood*
D007211:Indoles; D000331:Aequorin; C048960:indo-1; D002118:Calcium