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 A2 (TxA2)], and impaired [14C]serotonin secretion in response to collagen and U46619. The production of TxB2 (the stable TxA2 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 TxB2 production and U46619 response prompted further investigation of TxA2 receptor number and binding characteristics. Immunoblotting using an anti-TxA2 receptor antibody (anti-P2) identified a single, identical 55-kD band in solubilized membranes of control, full-term, and preterm platelets. Flow cytometry using anti-P2 produced histograms that did not differ between adults and neonates. Ligand binding studies using [3H]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 Kd 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 TxA2 production and response. The poor response is not related to altered binding characteristics of the TxA2 receptor but may lie in the postreceptor signal transduction pathway.
Israels
S J
SJ
Departments of Pediatrics, Manitoba Institute of Cell Biology, University of Manitaba, Winnipeg, Canada.
Odaibo
F S
FS
Robertson
C
C
McMillan
E M
EM
McNicol
A
A
D000328:Adult; D000704:Analysis of Variance; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005865:Gestational Age; D006801:Humans; D015151:Immunoblotting; D007231:Infant, Newborn / Q000097:blood; D007234:Infant, Premature / Q000097:blood*; D008297:Male; D010974:Platelet Aggregation / Q000502:physiology; D011869:Radioligand Assay; D012701:Serotonin / Q000378:metabolism; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis; D013931:Thromboxanes / Q000096:biosynthesis* / Q000097:blood
D013931:Thromboxanes; D012701:Serotonin; D013929:Thromboxane B2; D013928:Thromboxane A2