Summary
Platelet aggregation induced by ADP can be inhibited by plasma from uremic patients
or by toxins isolated from their plasma, e. g. guanidinosuccinic acid, methylguanidine,
phenol and hydroxyphenylacetic acids. Since these chemical substances can interfere
with energy metabolism in tissues other than platelets and since ATP production is
needed for ADP-induced aggregation, alterations in platelet energy metabolism could
underlie excessive bleeding in uremic patients. Platelets incubated with idioacetate
and deprived of anaerobic glycolysis produced the same quantity of ATP through respiration
in the presence of all the uremic toxins studied as in their absence. Similarly, platelets
incubated with cyanide and deprived of the oxidative pathway utilized anaerobic glycolysis
to produce normal quantities of ATP in the presence of all the uremic toxins. The
utilization of ATP, as indicated by active transmembrane potassium transport, was
also unaffected by the above listed guanidines and phenols. It is concluded that the
in vitro inhibition of ADP-induced platelet aggregation by the guanidines and phenols studied
is not due to inhibition of production or utilization of ATP.
