Seminars in Hematology
Volume 47, Issue 3 , Pages 281-288 , July 2010

Neonatal Thrombocytopenia and Megakaryocytopoiesis

References 

  1. Wiedmeier SE, Henry E, Sola-Visner MC, Christensen RD. Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J Perinatol. 2009;29:130–136
  2. Dreyfus M, Kaplan C, Verdy E, Schlegel N, Durand-Zaleski I, Tchernia G. Frequency of immune thrombocytopenia in newborns: a prospective study (Immune thrombocytopenia working group). Blood. 1997;89:4402–4406
  3. Castle V, Andrew M, Kelton J, Giron D, Johnston M, Carter C. Frequency and mechanism of neonatal thrombocytopenia. J Pediatr. 1986;108:749–755
  4. Mehta P, Vasa R, Neumann L, Karpatkin M. Thrombocytopenia in the high-risk infant. J Pediatr. 1980;97:791–794
  5. Christensen RD, Henry E, Wiedmeier SE, et al. Thrombocytopenia among extremely low birth weight neonates: data from a multihospital healthcare system. J Perinatol. 2006;26:348–353
  6. Baer VL, Lambert DK, Henry E, Christensen RD. Severe thrombocytopenia in the nicu. Pediatrics. 2009;124:e1095–e1100
  7. Stanworth SJ, Clarke P, Watts T, et al. Prospective, observational study of outcomes in neonates with severe thrombocytopenia. Pediatrics. 2009;124:e826–e834
  8. Lupton BA, Hill A, Whitfield MF, Carter CJ, Wadsworth LD, Roland EH. Reduced platelet count as a risk factor for intraventricular hemorrhage. Am J Dis Child. 1988;142:1222–1224
  9. Bussel JB, Sola-Visner M. Current approaches to the evaluation and management of the fetus and neonate with immune thrombocytopenia. Semin Perinatol. 2009;33:35–42
  10. Josephson CD, Su LL, Christensen RD, et al. Platelet transfusion practices among neonatologists in the united states and canada: results of a survey. Pediatrics. 2009;123:278–285
  11. Del Vecchio A, Sola MC, Theriaque DW, et al. Platelet transfusions in the neonatal intensive care unit: factors predicting which patients will require multiple transfusions. Transfusion. 2001;41:803–808
  12. Dohner ML, Wiedmeier SE, Stoddard RA, et al. Very high users of platelet transfusions in the neonatal intensive care unit. Transfusion. 2009;49:869–872
  13. Kenton AB, Hegemier S, Smith EO, et al. Platelet transfusions in infants with necrotizing enterocolitis do not lower mortality but may increase morbidity. J Perinatol. 2005;25:173–177
  14. Bonifacio L, Petrova A, Nanjundaswamy S, Mehta R. Thrombocytopenia related neonatal outcome in preterms. Indian J Pediatr. 2007;74:269–274
  15. Baer VL, Lambert DK, Henry E, Snow GL, Sola-Visner MC, Christensen RD. Do platelet transfusions in the NICU adversely affect survival? (Analysis of 1600 thrombocytopenic neonates in a multihospital healthcare system). J Perinatol. 2007;27:790–796
  16. Sola MC, Juul SE, Meng YG, et al. Thrombopoietin (tpo) in the fetus and neonate: Tpo concentrations in preterm and term neonates, and organ distribution of tpo and its receptor (c-mpl) during human fetal development. Early Hum Dev. 1999;53:239–250
  17. Murray NA, Watts TL, Roberts IA. Endogenous thrombopoietin levels and effect of recombinant human thrombopoietin on megakaryocyte precursors in term and preterm babies. Pediatr Res. 1998;43:148–151
  18. Walka MM, Sonntag J, Dudenhausen JW, Obladen M. Thrombopoietin concentration in umbilical cord blood of healthy term newborns is higher than in adult controls. Biol Neonate. 1999;75:54–58
  19. Nishihira H, Toyoda Y, Miyazaki H, Kigasawa H, Ohsaki E. Growth of macroscopic human megakaryocyte colonies from cord blood in culture with recombinant human thrombopoietin (c-mpl ligand) and the effects of gestational age on frequency of colonies. Br J Haematol. 1996;92:23–28
  20. Olson TA, Levine RF, Mazur EM, Wright DG, Salvado AJ. Megakaryocytes and megakaryocyte progenitors in human cord blood. Am J Pediatr Hematol Oncol. 1992;14:241–247
  21. Allen Graeve JL, de Alarcon PA. Megakaryocytopoiesis in the human fetus. Arch Dis Child. 1989;64:481–484
  22. de Alarcon PA, Graeve JL. Analysis of megakaryocyte ploidy in fetal bone marrow biopsies using a new adaptation of the feulgen technique to measure DNA content and estimate megakaryocyte ploidy from biopsy specimens. Pediatr Res. 1996;39:166–170
  23. Mattia G, Vulcano F, Milazzo L, et al. Different ploidy levels of megakaryocytes generated from peripheral or cord blood CD34+ cells are correlated with different levels of platelet release. Blood. 2002;99:888–897
  24. Slayton WB, Wainman DA, Li XM, et al. Developmental differences in megakaryocyte maturation are determined by the microenvironment. Stem Cells. 2005;23:1400–1408
  25. Ignatz M, Sola-Visner M, Rimsza LM, et al. Umbilical cord blood produces small megakaryocytes after transplantation. Biol Blood Marrow Transplant. 2007;13:145–150
  26. Gutti R SH, Bailey M, Liu ZJ, Sola-Visner M. Neonatal and adult megakaryocytes have different microRNA expression profiles, which might contribute to their biological differences. Society of Pediatric Research Meeting E-PAS. 2009;2730.4
  27. Watts TL, Murray NA, Roberts IA. Thrombopoietin has a primary role in the regulation of platelet production in preterm babies. Pediatr Res. 1999;46:28–32
  28. Sola MC, Calhoun DA, Hutson AD, Christensen RD. Plasma thrombopoietin concentrations in thrombocytopenic and non-thrombocytopenic patients in a neonatal intensive care unit. Br J Haematol. 1999;104:90–92
  29. Brown RE, Rimsza LM, Pastos K, et al. Effects of sepsis on neonatal thrombopoiesis. Pediatr Res. 2008;64:399–404
  30. Colarizi P, Fiorucci P, Caradonna A, Ficuccilli F, Mancuso M, Papoff P. Circulating thrombopoietin levels in neonates with infection. Acta Paediatr. 1999;88:332–337
  31. Sola MC, Slayton WB, Rimsza LM, et al. A neonate with severe thrombocytopenia and radio-ulnar synostosis. J Perinatol. 2004;24:528–530
  32. Harker LA. Kinetics of thrombopoiesis. J Clin Invest. 1968;47:458–465
  33. Harker LA, Finch CA. Thrombokinetics in man. J Clin Invest. 1969;48:963–974
  34. Sola-Visner MC, Christensen RD, Hutson AD, Rimsza LM. Megakaryocyte size and concentration in the bone marrow of thrombocytopenic and nonthrombocytopenic neonates. Pediatr Res. 2007;61:479–484
  35. Hu Z, Slayton WB, Rimsza LM, Bailey M, Sallmon H, Sola-Visner MC. Differences between newborn and adult mice in their response to immune thrombocytopenia. Neonatology. 2010;98:100–108
  36. Sola MC, Du Y, Hutson AD, Christensen RD. Dose-response relationship of megakaryocyte progenitors from the bone marrow of thrombocytopenic and non-thrombocytopenic neonates to recombinant thrombopoietin. Br J Haematol. 2000;110:449–453
  37. Pastos KM, Slayton WB, Rimsza LM, Young L, Sola-Visner MC. Differential effects of recombinant thrombopoietin and bone marrow stromal-conditioned media on neonatal versus adult megakaryocytes. Blood. 2006;108:3360–3362
  38. Sola MC, Christensen RD, Hutson AD, Tarantal AF. Pharmacokinetics, pharmacodynamics, and safety of administering pegylated recombinant megakaryocyte growth and development factor to newborn rhesus monkeys. Pediatr Res. 2000;47:208–214
  39. Liu ZJBM, Gutti R, Sallmon H, Sola-Visner M. Thrombopoietin stimulates the cytoplasmic maturation of low-ploidy neonatal megakaryocytes through the mTOR pathway. Society of Pediatric Research Meeting E-PAS. 2009;2730.1
  40. Murray NA, Howarth LJ, McCloy MP, Letsky EA, Roberts IA. Platelet transfusion in the management of severe thrombocytopenia in neonatal intensive care unit patients. Transfus Med. 2002;12:35–41
  41. Garcia MG, Duenas E, Sola MC, Hutson AD, Theriaque D, Christensen RD. Epidemiologic and outcome studies of patients who received platelet transfusions in the neonatal intensive care unit. J Perinatol. 2001;21:415–420
  42. Erhardt JA, Erickson-Miller CL, Aivado M, Abboud M, Pillarisetti K, Toomey JR. Comparative analyses of the small molecule thrombopoietin receptor agonist eltrombopag and thrombopoietin on in vitro platelet function. Exp Hematol. 2009;37:1030–1037
  43. Aher SM, Ohlsson A. Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database. 2006;3:CD004865
  44. Liu H, Jia D, Fu J, et al. Effects of granulocyte colony-stimulating factor on the proliferation and cell-fate specification of neural stem cells. Neuroscience. 2009;164:1521–1530
  45. Dame C, Wolber EM, Freitag P, Hofmann D, Bartmann P, Fandrey J. Thrombopoietin gene expression in the developing human central nervous system. Brain Res Dev Brain Res. 2003;143:217–223
  46. Ehrenreich H, Hasselblatt M, Knerlich F, et al. A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain. Proc Natl Acad Sci U S A. 2005;102:862–867
  47. Samoylenko A, Byts N, Rajalingam K, et al. Thrombopoietin inhibits nerve growth factor-induced neuronal differentiation and erk signalling. Cell Signal. 2008;20:154–162

 Supported in part by National Institutes of Health Grant No. HL69990 (M.S.V.) and Grant No. BAE-90058 from the Health Research Fund, Ministry of Health, Spain and a Health Service grant from the Comunidad Autonoma of Murcia, Spain (both F.F.M.)

PII: S0037-1963(10)00058-2

doi: 10.1053/j.seminhematol.2010.04.002

Seminars in Hematology
Volume 47, Issue 3 , Pages 281-288 , July 2010