- Email: [email protected]
Ticlopidine facilitates the deaggregation of human platelets aggregated by thrombin
90
ABSTRACTS
Suppl. XIII, 1991
179 TICLOPIDINE PLATELETS TO Cimminiellof,
SELECTIVELY INHIBITS THE RESPONSES OF HUMAN ADP. M, Cattaneo, B. Akkawat, A. Lecchi, C. "A Bianchi Bonomi" Hemophilia and P.M. Mannucci.
Thrombosis Center; *Medicina IV, S. Carlo Hospital. Milano. It has been purported that ticlopidine (T) induces a "functionally thrombasthenic state" (Di Minno et al, JCI 1985), since it inhibits platelet aggregation (PA) and fibrinogen (Fg) binding induced by ADP and by agonists causing the release of endogenous ADP. We studied 15 patients with TIA or stroke before and 7 days after ~5~1 administration of T (250 mg b.i.d.). T inhibited PA and I-Fg binding induced by ADP (20 umol/L), did not inhibit PA but ;::;:8,;; ~;;;b/;;ei-l~gllagen (5. ug/ml), I-Fg binding induced by thrombin (Iv/ml). The same pattern of inhibition was caused in vitro by the ADP scavengers apyrase or CP1/C$K plus ATP (1 mmol/L). T did not further inhibit PA and I-Fg binding in presence of ADP scavengers. U46619 or thrombin, but not ADP, increased the rate of binding to T-treated platelets of anti-GPIIb/IIIa MoAb 7E3. T did not inhibit clot retraction induced by thrombin (5 U/ml) or by reptilase plus epinephrine (5 umol/L) but inhibited clot retraction induced by reptilase plus ADP (5 umol/L). T prevented the inhibitory effect of ADP, but not of epinephrine on PGEl induced increase of platelet cyclic AMP. Thus, T selectively inhibits the platelet responses to ADP, rather than inducing a functionally thrombasthenic state. 180 TICLOPIDINE FACILITATES THE DEAGGREGATION OF HUMAN PLATELETS AGGREGATED BY THROMBIN. A. Lecchi, M. Cattaneo, B. Akkawat, C. "A. Bianchi Bonomi" Hemophilia and Cimminiello*, P.M. Mannucci.
Thrombosis Center. *Medicina IV, S. Carlo Hospital. Milano. Normal human platelets aggregated by thrombin undergo the release reaction and are not readly deaggregated by the and chymotrypsin. We combination of inhibitors hirudin, PGE have shown that released ADP stabil 1 zes thrombin-induced platelet aggregates. Since ticlopidine selectively inhibits the studied thrombin-induced platelet responses to ADP, we14 C-labeled washed platelets aggregation and deaggregation of from 5 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stipulated with thrombin C-serotonin and did (1 U/ml) aggregated, released about 90% not deaggregate spontaneously. Before ticlopidine, the addition (10 of hirudin (5 U/mL), PGEl (10 umol/L) plus chymotrypsin U/mL) to platelet suspensions 2 min after stimulation with thrombin did not cause the deaggregation of platelets. In contrast, after ticlopidine administration, the same inhibitors caused 40% deaggreagation within 3 min. ADP (10 ,umol/L) added to platelet suspensions 5 set after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Therefore, ticlopidine facilitates the deaggregation of thrombin-induced platelet aggregates.
ABSTRACTS
Suppl. XIII, 1991
179 TICLOPIDINE PLATELETS TO Cimminiellof,
SELECTIVELY INHIBITS THE RESPONSES OF HUMAN ADP. M, Cattaneo, B. Akkawat, A. Lecchi, C. "A Bianchi Bonomi" Hemophilia and P.M. Mannucci.
Thrombosis Center; *Medicina IV, S. Carlo Hospital. Milano. It has been purported that ticlopidine (T) induces a "functionally thrombasthenic state" (Di Minno et al, JCI 1985), since it inhibits platelet aggregation (PA) and fibrinogen (Fg) binding induced by ADP and by agonists causing the release of endogenous ADP. We studied 15 patients with TIA or stroke before and 7 days after ~5~1 administration of T (250 mg b.i.d.). T inhibited PA and I-Fg binding induced by ADP (20 umol/L), did not inhibit PA but ;::;:8,;; ~;;;b/;;ei-l~gllagen (5. ug/ml), I-Fg binding induced by thrombin (Iv/ml). The same pattern of inhibition was caused in vitro by the ADP scavengers apyrase or CP1/C$K plus ATP (1 mmol/L). T did not further inhibit PA and I-Fg binding in presence of ADP scavengers. U46619 or thrombin, but not ADP, increased the rate of binding to T-treated platelets of anti-GPIIb/IIIa MoAb 7E3. T did not inhibit clot retraction induced by thrombin (5 U/ml) or by reptilase plus epinephrine (5 umol/L) but inhibited clot retraction induced by reptilase plus ADP (5 umol/L). T prevented the inhibitory effect of ADP, but not of epinephrine on PGEl induced increase of platelet cyclic AMP. Thus, T selectively inhibits the platelet responses to ADP, rather than inducing a functionally thrombasthenic state. 180 TICLOPIDINE FACILITATES THE DEAGGREGATION OF HUMAN PLATELETS AGGREGATED BY THROMBIN. A. Lecchi, M. Cattaneo, B. Akkawat, C. "A. Bianchi Bonomi" Hemophilia and Cimminiello*, P.M. Mannucci.
Thrombosis Center. *Medicina IV, S. Carlo Hospital. Milano. Normal human platelets aggregated by thrombin undergo the release reaction and are not readly deaggregated by the and chymotrypsin. We combination of inhibitors hirudin, PGE have shown that released ADP stabil 1 zes thrombin-induced platelet aggregates. Since ticlopidine selectively inhibits the studied thrombin-induced platelet responses to ADP, we14 C-labeled washed platelets aggregation and deaggregation of from 5 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stipulated with thrombin C-serotonin and did (1 U/ml) aggregated, released about 90% not deaggregate spontaneously. Before ticlopidine, the addition (10 of hirudin (5 U/mL), PGEl (10 umol/L) plus chymotrypsin U/mL) to platelet suspensions 2 min after stimulation with thrombin did not cause the deaggregation of platelets. In contrast, after ticlopidine administration, the same inhibitors caused 40% deaggreagation within 3 min. ADP (10 ,umol/L) added to platelet suspensions 5 set after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Therefore, ticlopidine facilitates the deaggregation of thrombin-induced platelet aggregates.