Hemorrhagic complications occur in neonates, including intraventricular hemorrhage (IVH) in premature babies. The premature infant appears to be at greatest risk for a head bleed from days 2–3 until day 7 after birth. A relationship exists that suggests that the shorter the gestation, the greater the risk for this potentially fatal hemorrhagic event. The basis of intra-ventricular brain hemorrhage (IVH) in the premature infant is unknown. Premature birth is not necessarily the cause of IVH. The neonate is known to have a transient platelet dysfunction at the time of birth. Studies to define the transient platelet dysfunction in the neonate have been limited. Explanations in the literature include:
a diminished response to physiologic agonists,
defective platelet (PL) dense granule (DG) secretion, and/or
ineffective mobilization of intracellular calcium in platelets.
We and others have found that the adenine nucleotide content of platelets obtained from umbilical cord blood is significantly less than seen in adults. We have found that platelets obtained from umbilical cord blood have an average of 0.79±0.08 DG/PL (n=62), which is significantly decreased compared to the adult population (4–6 DG/PL) (
Blood, 100(11):691a, 2002
). Although the concentration of ADP and ATP were found to be decreased compared to normal adult platelets, the ATP/ADP ratio in neonatal platelets is 1.95 (n=61), consistent with established adult normal range ratio values (1.4–1.95). The current studies are ultimately intended to evaluate infants that have survived severe IVH for platelet dysfunction due to platelet dense granule deficiency (δ-SPD). Preliminary data have been obtained on peripheral blood from premature infants (n=15) obtained 3–5 d after birth. Their values (mean±2sd) are: gestational age 31±4.8 weeks and wt 1506±474 gr. The DG number (1.01±0.16/PL) is significantly decreased compared to normal adults, while the ATP (3.19±0.36 μM/1011 PL), ADP (2.63±0.54 μM/1011 PL) and ATP/ADP ratio (1.46±0.13) are normal. The decreased DG number in premature PL is strikingly similar to the DG content in cord blood PLs. We have studied one infant’s cord blood (2.41 DG/PL)and day 1 peripheral blood (3.87 DG/PL). The parents have had a normal DG number and adenine nucleotide content. These results would suggest that the premature infant platelets may have an incomplete incorporation of calcium into the dense granules 3–5 days after birth when compared to the normal adenine nucleotide content. A decrease in DG calcium would explain the decreased numbers of DGs calculated from whole mounted PLs by EM. Calcium is electron dense and if lacking in DGs, would result in an artificially low number of DGs determined by this method. To date, we have not obtained blood from a premature infant with a significant IVH or its parents to evaluate δ-SPD as a potential etiology of severe IVH.
