Ticlopidine facilitates the deaggregation of human platelets aggregated by thrombin.
Normal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80-90% 14C-serotonin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5x the activity of thrombin) and PGE1 (10 mumol/l) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 mumol/l) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.
Cattaneo
M
M
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Italy.
Akkawat
B
B
Kinlough-Rathbone
R L
RL
Packham
M A
MA
Cimminiello
C
C
Mannucci
P M
PM
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D000527:Alprostadil / Q000494:pharmacology; D002918:Chymotrypsin / Q000494:pharmacology; D005260:Female; D005341:Fibrinolysin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology; D013988:Ticlopidine / Q000494:pharmacology*
D006629:Hirudins; D000244:Adenosine Diphosphate; D002918:Chymotrypsin; D013917:Thrombin; D005341:Fibrinolysin; D000527:Alprostadil; D013988:Ticlopidine