Deficient thromboxane synthesis and response in platelets from premature infants

in vitro function of cord blood platelets from 35 premature infants (gestational age 32 +/- 3.2 wk) was compared with that of 12 full-term infants and 14 adult control subjects. In comparison with adult platelets, preterm platelets showed impaired aggregation, in response to thrombin, collagen, ADP, and U46619 [a stable analog of thromboxane A(2) (TxA(2))], and impaired [C-14]serotonin secretion in response to collagen and U46619. The production of TxB(2) (the stable TxA(2) metabolite) in response to collagen was reduced in preterm platelets (30.2 +/- 5.5 ng/mL) compared with full-term (52.7 +/- 12.6 ng/mL) or adult control platelets (132.3 +/- 38.7 ng/mL). The deficient TxB(2) production and U46619 response prompted further investigation of TxA(2) receptor number and binding characteristics. Immunoblotting using an anti-TxA(2) receptor antibody (anti-P-2) identified a single, identical 55-kD band in solubilized membranes of control, fullterm, and preterm platelets. Flow cytometry using anti-P-2 produced histograms that did not differ between adults and neonates. Ligand binding studies using [H-3]U46619 were carried out on 10 samples from each group. Scatchard analysis yielded a single class of binding sites with no significant difference among the K-d values (85 +/- 16 versus 99 +/- 12 versus 100 +/- 12 nM) or number of binding sites per platelet (1876 +/- 460 versus 2450 +/- 478 versus 2777 +/- 536) for preterm and full-term infants and adults. Therefore platelets of preterm infants show impaired TxA(2) production and response. The poor response is not related to altered binding characteristics of the TxA(2) receptor but may lie in the postreceptor signal transductian pathway.