Are There Developmental Changes in Platelet Function for Children?

Patient Presentation
The new clinical medical student was rounding with the general pediatric inpatient team. She presented a 3-day-old, 37 0/7 week male who had been admitted for hyperbilirubinemia. She noted that the brother had had hyperbilirubinemia as well, and also had thrombocytopenia. “Apparently it was worked up but the parents said nothing was found. We did a CBC too and the platelet count was 149,000. It’s just below normal. I haven’t had a chance to ask if we need to worry about this. I think babies can have some different laboratory values but I don’t really know,” she said.

Discussion
While most people realize that each stage of a child’s life is different, there are some areas that people do not realize are different. For example, there are many laboratory values which are different based on the age because there are developmental changes. Within the hematopoietic system there are many developmental changes that are common such as hemoglobin and hematocrit. Others are less well known such as children have quantitatively less fibrinogen, but the activity is the same as adult fibrinogen.

Platelets are an important part of both the primary and secondary hemostasis processes. They develop from megakaryocytes in the bone marrow, and circulate in the blood with a lifespan of 7-10 days. “Following a vascular injury, platelets are activated by collagen exposed from the endothelium and engagement with von Willebrand factor (vWF), and this initiates subsequent formation of the hemostatic plug.” More platelets arrive at the vascular injury and they are cross-linked by fibrin to stabilize the plug.

There are many tests that can be done to evaluate platelet function including platelet function analysis-100/200 which is one of the standards for assessment ofprimary hemostasis in children, thromboelastrometry, flow cytometry, platelet ELISA assay and others.

Learning Point
Developmental changes for platelets in children includes:

    Platelet count

    Around 22 weeks gestation, the fetal platelet count reaches adult levels.
    Preterm infants have platelet counts between 150-450 x 1000/mm2 with the adult normal value 150 – 350 x 1000/mm2.
    Preterm infants (up to 70%) often have thrombocytopenia (platelet count below 150 x 1000/mm2) though. It is believed to be caused by a transient decrease in survivability in at least 20% of premature infants.
    Thrombopoietin is the major platelet hemostasis regulator of platelet production. It is detectable at all gestational ages and some studies have found premature infants having higher levels than term infants.

    A differential diagnosis of thrombocytopenia can be found here.
    A differential diagnosis of thrombocytosis can be found here.

    Platelet function

    Preterm infants have a higher risk of bleeding problems particularly intraventricular hemorrhage. There are many reasons for this including blood vessel fragility, but decreased platelet functioning is part of the problem. Major studies of platelet function in preterm infants have not been conducted relative to full-term infants because of the difficulties of obtaining blood from preterm infants and the large volumes needed to perform the testing. Phlebotomy is also a cause of anemia in preterm infants.
    Both platelet aggregation and platelet hyporeactivity have been reported in neonates. There is also decreased platelet adhesion and some differences in how platelets interact with vWF have been noted. Neonates also have increased high molecular weight vWF which increases platelet adhesions and may help compensate for platelet activity.

    Full-term infants also have decreased platelet activation and aggregation relative to adults. Timing of when platelet function reaches adult levels depends on the study and ranges from a few weeks to up to 15 years. But most healthy children > 1 year of age have platelet aggregation similar to adults.

    A review of congenital platelet function abnormalities can be found here.
    A review of thrombophilias can be found here.

Questions for Further Discussion
1. What are causes of hyperbilirubinemia in infants? A review can be found here.
2. What causes anemia? A review can be found here.

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Platelet Disorders

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Matthews DC. Inherited disorders of platelet function. Pediatr Clin North Am. 2013;60(6):1475-1488. doi:10.1016/j.pcl.2013.08.004

Del Vecchio A, Motta M, Romagnoli C. Neonatal Platelet Function. Clin Perinatol. 2015;42(3):625-638. doi:10.1016/j.clp.2015.04.015

Hvas A-M, Favaloro EJ. Platelet function testing in pediatric patients. Expert Rev Hematol. 2017;10(4):281-288. doi:10.1080/17474086.2017.1293518

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa