Released adenosine diphosphate stabilizes thrombin-induced human platelet
aggregates
M Cattaneo, MT Canciani, A Lecchi, RL Kinlough-Rathbone, MA Packham, PM Mannucci and JF Mustard
A.Bianchi Bonomi Hemophilia and Thrombosis Center, Maggiore Hospital,
Milano, Italy.
Normal human platelets aggregated by thrombin undergo the release reaction
and are not readily deaggregated by the combination of inhibitors hirudin,
chymotrypsin, and prostaglandin E1 (PGE1). In contrast, thrombin-induced
aggregates of platelets from patients with delta-storage pool deficiency
(delta-SPD), which lack releasable nucleotides, are readily deaggregated by
the same combination of inhibitors. The ease with which delta-SPD platelets
are deaggregated is caused by the lack of stabilizing effects of released
ADP, since: (1) exogenous adenosine diphosphate (ADP) (10 mumol/L), but not
serotonin (2 mumol/L), abolishes the ability of these inhibitors to
deaggregate delta-SPD platelets; (2) thrombin-induced aggregates of
platelets from a patient (V.R.) (whose platelets have a severe, selective
impairment of sensitivity to ADP, but normal amounts of releasable
nucleotides) can be readily deaggregated, and addition of ADP does not
stabilize the platelet aggregates; (3) apyrase or creatine phosphate
(CP)/creatine phosphokinase (CPK), added before thrombin, make control
platelets more easily deaggregated by hirudin, chymotrypsin, and PGE1, and
do not change the deaggregation response of delta-SPD platelets and of
V.R.'s platelets. Thrombin-induced aggregation and release of beta-
thromboglobulin in control, delta-SPD, and in V.R.'s platelets was similar
and not inhibited by apyrase or CP/CPK. The stabilizing effect of ADP on
platelet aggregates is specific, since epinephrine in the presence of
apyrase to remove traces of released ADP does not stabilize the aggregates
of control, delta-SPD, or of V.R.'s platelets. Because epinephrine
increases fibrinogen binding to thrombin-stimulated platelets to a greater
extent than ADP, but does not stabilize the aggregates, it is unlikely that
the additional fibrinogen binding sites induced by ADP have a major role in
inhibiting deaggregation by the combination of inhibitors.
Volume 75,
Issue 5,
pp. 1081-1086,
03/01/1990
Copyright © 1990 by The American Society of Hematology
