The Platelet of the Newborn Infant – Adenine Nucleotide Metabolism and Release

Summary

Blood from normal full term infants, mothers and normal adults was collected in citrate. Citrated platelet-rich plasma was prelabelled with ³H-adenine and reacted with release inducers, collagen and adrenaline. Adenine nucleotide metabolism, total adenine nucleotide levels and changes in sizes of these pools were determined in platelets from these three groups of subjects.

At rest, the platelet of the newborn infant, compared to that of the mother and normal adult, possessed similar amounts of adenosine triphosphate (ATP), 4.6 ± 0.2 (SD), 5.0 ± 1.1, 4.9 ± 0.6 µmoles ATP/10¹¹ platelets respectively, and adenosine diphosphate (ADP), 2.4 ± 0.7, 2.8 ± 0.6, 3.0 ± 0.3 umoles ADP/10¹¹ platelets respectively. However the marked elevation of specific radioactivity of ADP and ATP in these resting platelets indicated the platelet of the neonate has decreased adenine nucleotide stores.

In addition to these decreased stores of adenine nucleotides, infant platelets showed significantly impaired release of ADP and ATP on exposure to collagen. The release of ADP in infants, mothers, and other adults was 0.9 ± 0.5 (SD), 1.5 ± 0.5, 1.5 ± 0.1 umoles/10¹¹ platelets respectively; that of ATP was 0.6 ± 0.3, 1.0 ± 0.1,1.3 ± 0.2 µmoles/10¹¹ platelets respectively. With collagen-induced release, platelets of newborn infants compared to those of other subjects showed only slight increased specific radioactivities of adenine nucleotides over basal levels. The content of metabolic hypoxanthine, a breakdown product of adenine nucleotides, increased in both platelets and plasma in all subjects studied.

In contrast, with adrenaline as release inducer, the platelets of the newborn infant showed no adenine nucleotide release, no change in total ATP and level of radioactive hypoxanthine, and minimal change in total ADP. The reason for this decreased adrenaline reactivity of infant platelets compared to reactivity of adult platelets is unknown.

Infant platelets may have different membranes, with resulting differences in regulation of cellular processes, or alternatively, may be refractory to catecholamines because of elevated levels of circulating catecholamines in the newborn period.

Keywords

Platelet - Newborn infant - Adenine nucleotide metabolism - Release reaction

• References

• 1 Stormorken H. The release reaction of secretion. Scand J Haematol Suppl 1969; 9: 1-24
• 2 Grette K. Studies on the mechanism of thrombin-catalyzed hemostatic reactions in blood platelets. Acta Physiol Scand 1962; 56 (Suppl 195) 1-93
• 3 Day HJ, Holmsen H. Concepts of the blood platelet release reaction. Ser Haematol 1971; 4: 3-27
• 4 Mürer EH, Day HJ. Observations on the platelet release reaction. Platelets and Thrombosis. In: Sherry S, Scriabine A. (ed.) University Park Press, Baltimore: 1974. p 1-22
• 5 Mustard JF, Packham MA. Factors influencing platelet function: adhesion, release and aggregation. Pharmacol Rev 1970; 22: 97-187
• 6 Holmsen H, Weiss HJ. Secretable storage pools in platelets. Ann Rev Med 1979; 30: 119-134
• 7 Haslam RJ. Role of adenosine diphosphate in the aggregation of human blood-platelets by thrombin and by fatty acids. Nature 1964; 202: 765-768
• 8 Holmsen H, Day HJ. Adenine nucleotides and platelet function. Ser Haematol 1971; 4: 28-58
• 9 Sutherland JM, Glueck HE, Gleser G. Hemorrhagic disease of the newborn. Am J Dis Child 1967; 113: 524-533
• 10 Harcke HT, Naeye RL, Storch A, Blanc WA. Perinatal cerebral intraventricular hemorrhage. J Pediatr 1972; 80: 37-42
• 11 Aballi AJ, De Lamerens S. Coagulation changes in the neonatal period and in early infancy. Pediatr Clin North Am 1962; 9: 785-817
• 12 Whaun JM. The platelet of the newborn infant – 5-hydroxytryptamine uptake and release. Thromb Diath Haemorrh 1973; 30: 327-333
• 13 Holmsen H, Ostvold AC, Day HJ. Behaviour of endogenous and newly absorbed serotonin in the platelet release reaction. Biochem Pharmacol 1973; 22: 2599-2608
• 14 Holmsen H, Storm E, Day HJ. Determination of ATP and ADP in blood platelets: a modification of the firefly luciferase assay for plasma. Anal Biochem 1972; 46: 489-501
• 15 Mull MM, Hathway WE. Altered platelet function in newborns. Pediatr Res 1970; 4: 229-237
• 16 Bleyer WA, Breckenridge RT. Studies on the detection of adverse drug reactions in the newborn. II. The effect of prenatal aspirin on newborn hemostasis. J Am Med Ass 1970; 213: 2049-2053
• 17 Corby DG, Schulman I. The effects of antenatal drug administration on aggregation of platelets of newborn infants. J Pediatr 1971; 79: 307-313
• 18 Corby DG, Shigeta FH, Zuck T. Speculations of the implications of newborn platelet defects. Abstract. The International Society on Thrombosis and Haemostasis. III Congress; 1972 p 180
• 19 Whaun JM, Smith GR, Sochor VA. Effect of prenatal drug administration on maternal and neonatal platelet aggregation and PF₄ release. Haemostasis 1980; 9: 226-237
• 20 Whaun JM, Holmsen H, Day HJ, Oski FA. The neonatal platelet release reaction. Abstract. American Society of Hematology, 13th Annual Meeting, December 1970 p 131
• 21 Holmsen H, Weiss HJ. Hereditary defect in the platelet release reaction caused by a deficiency in the storage pool of platelet adenine nucleotides. Br J Haematol 1970; 19: 643-649
• 22 Lages B, Scrutton MC, Holmsen H, Day HJ, Weiss HJ. Metal ion contents of gel-filtered platelets from patients with storage pool disease. Blood 1975; 46: 119-30
• 23 Comline RS, Silver M. Catecholamine secretion by adrenal medulla of the foetal and new-born foal. J Physiol 1971; 216: 659-682
• 24 Walsh PN, Gagnatelli G. Platelet antiheparin activity: storage site and release mechanism. Blood 1974; 44: 157-168
• 25 Weiss HJ, Rogers J. Platelet factor 4 in platelet disorders - storage location and the requirements of endogenous ADP for its release. Proc Soc Exp Biol Med 1973; 142: 30-35