Does Platelet Dysfunction Mediate the Development of Intraventricular Hemorrhage in the Premature Neonate?.
Authors: Siavosh Asmaneh S. , Stein Howard M. , Stein Dagmar T. , Ohler Sue , McCarthy Sean T. , Gunning William T. 
Published: April 2020

Abstract
The purpose of this investigation is to evaluate the potential of platelet dysfunction as a risk factor for the development of intraventricular hemorrhage (IVH) in the premature neonate. Intraventricular hemorrhage is relatively common, especially in infants weighing less than 1500 grs or less than 35 weeks of gestation. Neonates less than 32 weeks gestation are at significant risk for periventricular/intraventicular bleeding with mortality rates approaching 50% for those having a high grade (III-IV) IVH. The pathogenesis of IVH in the premature infant is thought to be related to loss of an ability to regulate cerebral blood flow (cerebral autoregulation) in the subependymal germinal matrix. This leads to abrupt changes in local blood pressure regulation and results in capillary bleeding. It is also apparent that birth weight and gestational age are not the only risk factors for IVH; relationships with lung development and ventilation, or lack thereof, also exist as risk factors.
In a previous study of platelets obtained from umbilical cord blood, we have found that the neonate has a transient platelet dysfunction at the time of birth which appears to be related to a platelet (PL) dense granule (DG) storage pool deficiency (δ-SPD). 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). We have data establishing that a one-day-old full-term neonate has adenine nucleotide values consistent with adult levels. We postulate that a failure of platelet maturation related to gestational age of the preterm neonate, or an inherent δ-SPD, may extend the platelet dysfunction at birth and should therefore be considered a potential risk factor for development of IVH in the premature neonate.
We have collected peripheral blood with informed consent from premature neonates, 26–33 weeks gestational age and their parents to assess the PL DG content and the adenine nucleotide content of each subject. Preliminary data (mean ± 2 SE) from the peripheral blood of premature infants (n=19) obtained 3–5 d after birth include: gestational age 30.18 ± 1.28 weeks and wt 1378.2 ± 27.8 gr. The DG number (1.00 ± 0.29/PL) is significantly decreased compared to normal adults, while the ATP (3.19 ± 0.36 M/1011 PL), ADP (2.63 ± 0.54 M/1011 PL) and ATP/ADP ratio (1.46 ± 0.13) are normal. The decreased DG number in premature PLs is essentially identical to the DG number in umbilical cord blood PLs. The parents studied to date have had a normal DG number and adenine nucleotide content. Our preliminary data suggests that at day 3–5 after birth, premature infants of gestational age 26–33 weeks have a δ-SPD similar to that observed in full-term umbilical cord blood PLs. Additional subjects are needed, especially premature neonates who have suffered a grade III or IV IVH to fully assess our hypothesis. A retrospective study of high-grade IVH survivors and their parents is currently being implemented to investigate an inherited δ-SPD mediator/risk factor for IVH in the premature neonate.