Activation of circulating platelets and platelet response to activating agents in children with cyanotic congenital heart disease: their relevance topalliative systemic-pulmonary shunt

Abnormal platelet function has been hypothesised to play a role in the haem ostatic abnormalities in cyanotic congenital heart disease (CCHD) patients. Using whole blood flow cytometry we found that platelets from cyanotic pat ients were hyperreactive and we related such hyperreactivity directly to yo ung age, unoperated state, high haematocrit, reduced saturation with oxygen and low platelet count. Circulating platelets from CCHD children showed si gnificantly enhanced P-selectin expression (P <0.004) and remained more rea ctive to 0.2 IU/ml thrombin, 1-8 muM TRAP and 2-4 muM ADP (P <0.04), especi ally in younger (0-3-year-olds) patients. Such a platelet 'priming' largely concerned CCHD children who were not subjected to modified Blalock-Taussig shunts in the past (non-MBTS). Only non-MBTS cyanotic children, but not MB TS-operated patients, showed significantly higher platelet reactivity compa red to controls in response to ADP or 1 muM TRAP with respect to P-selectin expression (p <0.05) and in response to all examined agonists with respect to GPIb expression (P <0.045). The enhanced P-selection expression in MBTS -operated CCHD children and reduced GPIb expression in non-MBTS patients, e specially in younger patients. were positively associated with the occurren ce of the polymorphic variant Pl(A2) of platelet membrane glycoprotein IIIa gene. Altered blood morphology parameters (elevated RBC, Hb, Hct and MCHC, for all P <0.0005) in CCHD children correlated with the enhanced degranula tion of circulating blood platelets and their hyperreactivity in response t o some agonists (P <0.05). Overall, our data encourage the reasoning that c irculating platelets are remarkably hyperreactive in non-MBTS cyanotic chil dren, which are at higher risk to often encounter platelets activation in c irculation. It seems unlikely that the apparently unchanged platelet reacti vity in MBTS-operated children is due to the advantageous effects of the sh unt, since these patients showed neither altered haematological parameters nor improved oxygen carrying capacity. Otherwise, it may rather result from more frequent episodes of platelet degranulation and preactivation in the past. and/or post-operative enhanced platelet consumption. (C) 2001 Elsevie r Science Ireland Ltd. All rights reserved.