Neonatal Thrombocytopenia and Megakaryocytopoiesis
Section snippets
Neonatal Thrombocytopenia
Platelets first appear in the human fetus at 5 weeks post-conception, and increase in number during fetal life, reaching a mean of 150 × 109/L by the end of the first trimester of pregnancy and normal adult values by 22 weeks of gestation. Since 22 weeks is the lowest gestational age at which a newborn infant is considered viable, this means that even the smallest and most immature infants cared for in neonatal intensive care units (NICUs) usually have platelet counts between 150 and 450 × 109
Neonatal Megakaryocytopoiesis
Over the last decade, a mounting body of evidence has led to the recognition of substantial biological differences between neonatal and adult megakaryocytopoiesis (see article by Geddis in this issue) (Table 1). While TPO appears to be the main thrombopoietic factor throughout life, its biology might be different at various stages of development. Unlike erythropoietin, which changes its main production site from the liver to the kidney during development, TPO is predominantly produced in the
The Response of Neonates to Thrombocytopenia
Recognition of these developmental differences in megakaryocytopoiesis led to the question of whether neonates respond to thrombocytopenia in a manner similar to adults, or whether the biological characteristics of their megakaryocytes limit their ability to upregulate platelet production during increased demand. In this regard, initial studies observed that preterm neonates with moderate thrombocytopenia due to intrauterine chronic hypoxia exhibited low numbers of marrow megakaryocytes and of
Effects of Tpo on Neonatal Megakaryocytopoiesis
While considering the introduction of thrombopoietic agents into neonatal medicine, an important question remains whether TPO or TPO mimetics can overcome the developmental limitations described above and increase platelet production in thrombocytopenic neonates. While this remains to be tested, several studies have documented substantial qualitative and quantitative differences in the response of neonatal megakaryocytes and megakaryocyte progenitors to TPO. In vitro, TPO stimulates the
Potential Use of Tpo Mimetics in Neonatology
In 2008, the US Food and Drug Administration approved the use of two novel TPO receptor agonists, romiplostim (AMG-531, Nplate, Amgen, Inc, Thousand Oaks, CA) and eltrombopag (SB497115, Promacta, GlaxoSmithKline, Middlesex, UK), for the treatment of adults with chronic idiopathic thrombocytopenia (ITP) not responsive to standard treatment (see article by Kuter in this issue). Although initially restricted to the second-line treatment of ITP in adult patients, it is anticipated that both agents
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Cited by (46)
Iron status influences the response of cord blood megakaryocyte progenitors to eltrombopag in vitro
2022, Blood AdvancesCitation Excerpt :For both cell sources, the maximal number of MKs (CD41+ cells) generated with ELT was lower than that achieved with TPO (P = .03 and .002 for CB and PB, respectively) or ROM (supplemental Figure 1A). At all TPO, ROM, or ELT concentrations, CB-MKs exhibited lower ploidy levels (supplemental Figure 1B) but higher percentages of CD42b+ MKs (a mature MK marker) than PB cultures (supplemental Figure 1C), consistent with the previously described pattern of neonatal megakaryopoiesis.11,12 In these cultures, ELT concentrations ≤6 µM increased MK counts, but cultures containing 30 µM ELT exhibited substantial cell death.
Platelet function in the newborn
2019, PlateletsThrombocytopenia in the newborn
2019, PlateletsErythropoietin and thrombopoietin mimetics: Natural alternatives to erythrocyte and platelet disorders
2016, Critical Reviews in Oncology/HematologyCitation Excerpt :The amount of circulating TPO is found to be low when the number of platelets are low, inducing its production (Kuter, 2010). The alteration in average platelet count results in different disorder (Ferrer-Marin et al., 2010). The increase in the number of platelets (>450,000/μL) leads to thrombocythemia, whereas the reduction (<150,000/μL) leads to thrombocytopenia.
Thrombocytopenia and platelet transfusion in the neonate
2016, Seminars in Fetal and Neonatal MedicineCitation Excerpt :In 1994, thrombopoietin was identified as the major regulator of megakaryopoiesis. Several studies analyzed the relationship between thrombopoietin concentrations during thrombocytopenia in neonates showing an increased concentration of circulating thrombopoietin [87,88]. After the disastrous introduction of full-length recombinant human thrombopoietin as a drug to stimulate megakaryopoiesis, which led to the formation of anti- thrombopoietin antibodies in healthy volunteers [89], two thrombopoietin receptor agonists were developed.