New Insights into the Mechanisms of Nonimmune Thrombocytopenia in Neonates

Abstract

Thrombocytopenia affects up to 35% of all patients admitted to the neonatal intensive care unit (NICU). The causes of thrombocytopenia in neonates are very diverse, and include immune and nonimmune disorders. Most cases of thrombocytopenia encountered in the NICU are non-immune, and these will constitute the focus of this review. Specifically, we will first discuss the biological differences between neonatal and adult megakaryocytopoiesis, which contribute to explain the vulnerability of neonates to develop thrombocytopenia. Next, we will review new diagnostic tools that have allowed for a better evaluation of platelet production in neonates, without having to obtain a bone marrow sample. Finally, we will summarize our current understanding of the mechanisms underlying the thrombocytopenia in several common neonatal conditions, such as chronic intrauterine hypoxia, sepsis and necrotizing enterocolitis (NEC), and viral infections. A better understanding of the mechanisms underlying these varieties of thrombocytopenia is critical to develop disease-specific treatment protocols, and to begin to entertain the possibility of using novel thrombopoietic growth factors to treat selected neonates with severe thrombocytopenia. Platelet production in neonatesPlatelet production, or thrombopoiesis, is a complex process that can be schematically represented as consisting of four main steps. The first step is the production of the thrombopoietic stimulus, which drives the generation of megakaryocytes and ultimately platelets. Although a number of cytokines (i.e. IL-3, IL-6, IL-11, GM-CSF) and chemokines (i.e. SDF and FGF-4) contribute to this process, thrombopoietin (Tpo) is now widely recognized as the most potent known stimulator of platelet production. Thrombopoietin mostly acts by promoting the proliferation of megakaryocyte progenitors (the cells that multiply and give rise to megakaryocytes), and the maturation of the megakaryocytes. 1-3 Megakaryocyte maturation is a process characterized by a progressive increase in nuclear ploidy and cytoplasmic maturity that leads to the generation of large polyploid (8N-64N) megakaryocytes. Through a still poorly understood process, these mature megakaryocytes then generate and release new platelets into the circulation. 4-6 Address correspondence to: Martha Sola-Visner, MD, Assistant Professor of Pediatrics, Children's Hospital Boston, Division of Newborn Medicine, 300 Longwood Av., Enders Research Building, Rm. 961, Boston, MA 02115, Phone: 617-919-4845, Fax: 617-730-0260, Email: E-mail: Martha.Sola-Visner@childrens.harvard.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal di...

MicroRNA‐9 promotes cell proliferation by regulating RUNX1 expression in human megakaryocyte development

“…6,7 It is believed that developmental differences between neonatal and adult MKs contribute to this vulnerability. 8 Specifically, neonatal MK progenitors possess a high proliferative potential and give rise to MKs smaller and of low ploidy that generate fewer platelets compared with adult MKs. The regulatory mechanisms underlying these developmental differences are unknown, but we have revealed a critical role of small non-coding RNAs (miRNAs) in the regulation of MK development.…”

Thrombocytopenia: Diagnostic Tool of Neonatal Infection?

“…The implemented study showed that out of 136 newborn who had thrombocytopenia, 34.6% mothers went through some type of complication during labor, such as: narrower pelvis, intrauterine infection, bleeding in the third stage of labor and so on. Placental insufficiency as risk factor for development of thrombocytopenia in the newborn in our study was found in 32.4% examinees, while some authors reduce the risk of thrombocytopenia development due to placental insufficiency to 1% [11]. In neonatological literature the above is explained by the fact that hypoxia in the newborn triggers abundant erythropoesis, which reduces the amount of progenitor cells needed for differentiation of megakaryocytes into thrombocytes [12].…”

Perbandingan Profil Hematologi dan Trombopoietin sebagai Petanda Sepsis Neonatorum Awitan Dini

“…12 Kadar TPO meningkat secara bermakna pada hari ke 4-5, dan tidak didapatkan perbedaan yang bermakna antara jumlah trombosit, TPO dan progenitor megakariosit pada bayi prematur. 31 Penelitian kami merupakan penelitian pertama yang membandingkan antara TPO dengan profil hematologi. Berdasarkan hasil analisis dengan ROC didapatkan area under curve (AUC) 51,3% dan nilai cut off TPO 259 pg/mL, dengan nilai sensitivitas 77,4%, spesifisitas 24,4%, NDP 63,6%, dan NDN 76,5%.…”