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 (δ-SPD), which lack releasable nucleotides, are readily deaggregated by the same combination of inhibitors. The ease with which δ-SPD platelets are deaggregated is caused by the lack of stabilizing effects of released ADP, since: (1) exogenous adenosine diphosphate (ADP) (10 μmol/L), but not serotonin (2 μmol/L), abolishes the ability of these inhibitors to deaggregate δ-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 δ-SPD platelets and of V.R.'s platelets. Thrombin-induced aggregation and release of β-thromboglobulin in control, δ-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, δ-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.
RELEASED ADENOSINE-DIPHOSPHATE STABILIZES THROMBIN-INDUCED HUMAN PLATELET AGGREGATES / M. CATTANEO, M. CANCIANI, A. LECCHI, R. KINLOUGHRATHBONE, M. PACKHAM, P. MANNUCCI, J. MUSTARD. - In: BLOOD. - ISSN 0006-4971. - 75:5(1990), pp. 1081-1086.
|Titolo:||RELEASED ADENOSINE-DIPHOSPHATE STABILIZES THROMBIN-INDUCED HUMAN PLATELET AGGREGATES|
CATTANEO, MARCO NATALE (Primo)
MANNUCCI, PIER MANNUCCIO (Penultimo)
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||1990|
|Appare nelle tipologie:||01 - Articolo su periodico|