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11 - Acquired thrombocytopenia

from Section III - Platelet disorders

Published online by Cambridge University Press:  05 February 2013

Pedro de Alarcón
Affiliation:
University of Illinois College of Medicine
Eric Werner
Affiliation:
Children's Hospital of the King's Daughters
Robert D. Christensen
Affiliation:
McKay-Dee Hospital, Utah
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Summary

Introduction

Over the last decades, as the survival of neonates admitted to the neonatal intensive care unit (NICU) improved, thrombocytopenia has become an increasingly important problem in the care of sick term and particularly preterm neonates. In this population, the majority of thrombocytopenias are due to acquired, non-immune processes, and most resolve with time and/or treatment of the underlying illness. Frequently, however, the etiology of the thrombocytopenia poses a diagnostic dilemma, and – if severe enough – places the affected neonate at risk of bleeding.

In this chapter, we will focus exclusively on acquired, non-immune thrombocytopenias that present in the neonatal period. First, we will review the incidence of neonatal thrombocytopenia, and will propose a classification based on timing and clinical presentation. We will then discuss the mechanisms underlying some of the most common varieties of neonatal thrombocytopenia, and how the biological differences between neonatal and adult megakaryocytes might contribute to the susceptibility of neonates to develop thrombocytopenia. Finally, we will offer recommendations for the management of non-immune thrombocytopenia in neonates, and will discuss the risks and benefits associated with platelet transfusions and with the potential future use of novel thrombopoiesis-stimulating factors in this population. Immune and congenital causes of neonatal thrombocytopenia are discussed in detail in Chapters 10 and 12, respectively.

Type
Chapter
Information
Neonatal Hematology
Pathogenesis, Diagnosis, and Management of Hematologic Problems
, pp. 157 - 171
Publisher: Cambridge University Press
Print publication year: 2013

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References

Aballi, AJ, Puapondh, Y, Desposito, F. Platelet counts in thriving premature infants. Pediatrics 1968;42:685–9.Google ScholarPubMed
Ablin, AR, Kushner, JH, Murphy, A, et al. Platelet enumeration in the neonatal period. Pediatrics 1961;28:822–4.Google ScholarPubMed
Sell, EJ, Corrigan, JJ, Jr. Platelet counts, fibrinogen concentrations, and factor V and factor VIII levels in healthy infants according to gestational age. J Pediatr 1973;82:1028–32.CrossRefGoogle ScholarPubMed
Wiedmeier, SE, Henry, E, Sola-Visner, MC, et al. Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J Perinatol 2009;29:130–6.CrossRefGoogle Scholar
McPherson, RJ, Juul, S. Patterns of thrombocytosis and thrombocytopenia in hospitalized neonates. J Perinatol 2005;25:166–72.CrossRefGoogle Scholar
Dreyfus, M, Kaplan, C, Verdy, E, et al. Frequency of immune thrombocytopenia in newborns: a prospective study. Immune Thrombocytopenia Working Group. Blood 1997;89:4402–6.Google ScholarPubMed
Uhrynowska, M, Maslanka, K, Zupanska, B. Neonatal thrombocytopenia: incidence, serological and clinical observations. Am J Perinatol 1997;14:415–18.CrossRefGoogle ScholarPubMed
Castle, V, Andrew, M, Kelton, J, et al. Frequency and mechanism of neonatal thrombocytopenia. J Pediatr 1986;108:749–55.CrossRefGoogle ScholarPubMed
Mehta, P, Vasa, R, Neumann, L, et al. Thrombocytopenia in the high-risk infant. J Pediatr 1980;97:791–4.CrossRefGoogle ScholarPubMed
Oren, H, Irken, G, Oren, B, et al. Assessment of clinical impact and predisposing factors for neonatal thrombocytopenia. Indian J Pediatr 1994;61:551–8.CrossRefGoogle ScholarPubMed
Christensen, RD, Henry, E, Wiedmeier, SE, et al. Thrombocytopenia among extremely low birth weight neonates: data from a multihospital healthcare system. J Perinatol 2006;26:348–53.CrossRefGoogle ScholarPubMed
Sola, MC, Slayton, WB, Rimsza, LM, et al. A neonate with severe thrombocytopenia and radio-ulnar synostosis. J Perinatol 2004;24:528–30.CrossRefGoogle ScholarPubMed
Tighe, P, Rimsza, LM, Christensen, RD, et al. Severe thrombocytopenia in a neonate with congenital HIV infection. J Pediatr 2005;146:408–13.CrossRefGoogle Scholar
Saxonhouse, MA, Manco-Johnson, MJ. The evaluation and management of neonatal coagulation disorders. Semin Perinatol 2009;33:52–65.CrossRefGoogle ScholarPubMed
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;43:148–51.CrossRefGoogle ScholarPubMed
Sola, MC, Calhoun, DA, Hutson, AD, et al. Plasma thrombopoietin concentrations in thrombocytopenic and non-thrombocytopenic patients in a neonatal intensive care unit. Br J Haematol 1999;104:90–2.CrossRefGoogle Scholar
Walka, MM, Sonntag, J, Dudenhausen, JW, et al. Thrombopoietin concentration in umbilical cord blood of healthy term newborns is higher than in adult controls. Biol Neonate 1999;75:54–8.CrossRefGoogle ScholarPubMed
Nishihira, H, Toyoda, Y, Miyazaki, H, et al. 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;92:23–8.CrossRefGoogle ScholarPubMed
Olson, TA, Levine, RF, Mazur, EM, et al. Megakaryocytes and megakaryocyte progenitors in human cord blood. Am J Pediatr Hematol Oncol 1992;14:241–7.CrossRefGoogle ScholarPubMed
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;39:166–70.CrossRefGoogle ScholarPubMed
Hegyi, E, Nakazawa, M, Debili, N, et al. Developmental changes in human megakaryocyte ploidy. Exp Hematol 1991;19:87–94.Google ScholarPubMed
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;99:888–97.CrossRefGoogle ScholarPubMed
Harker, LA. Kinetics of thrombopoiesis. J Clin Invest 1968;47:458–65.CrossRefGoogle ScholarPubMed
Harker, LA, Finch, CA. Thrombokinetics in man. J Clin Invest 1969;48:963–74.CrossRefGoogle ScholarPubMed
Sola-Visner, MC, Christensen, RD, Hutson, AD, et al. Megakaryocyte size and concentration in the bone marrow of thrombocytopenic and nonthrombocytopenic neonates. Pediatr Res 2007;61:479–84.CrossRefGoogle ScholarPubMed
Hu, ZSW, Rimsza, L, Bailey, M, Sallmon, H, Sola-Visner, M. Differences between newborn and adult mice in their response to immune thrombocytopenia. Neonatology In Press.
Kaushansky, K.Lineage-specific hematopoietic growth factors. N Engl J Med 2006;354:2034–45.CrossRefGoogle ScholarPubMed
Dame, C.Thrombopoietin in thrombocytopenias of childhood. Semin Thromb Hemost 2001;27:215–28.CrossRefGoogle ScholarPubMed
Murray, NA, Roberts, IA. Circulating megakaryocytes and their progenitors (BFU-MK and CFU-MK) in term and pre-term neonates. Br J Haematol 1995;89:41–6.CrossRefGoogle ScholarPubMed
Murray, NA, Roberts, IA. Circulating megakaryocytes and their progenitors in early thrombocytopenia in preterm neonates. Pediatr Res 1996;40:112–9.CrossRefGoogle ScholarPubMed
Ault, KA, Knowles, C. In vivo biotinylation demonstrates that reticulated platelets are the youngest platelets in circulation. Exp Hematol 1995;23:996–1001.Google ScholarPubMed
Ault, KA, Rinder, HM, Mitchell, J, et al. The significance of platelets with increased RNA content (reticulated platelets). A measure of the rate of thrombopoiesis. Am J Clin Pathol 1992;98:637–46.CrossRefGoogle ScholarPubMed
Joseph, MA, Adams, D, Maragos, J, et al. Flow cytometry of neonatal platelet RNA. J Pediatr Hematol Oncol 1996;18:277–81.CrossRefGoogle ScholarPubMed
Peterec, SM, Brennan, SA, Rinder, HM, et al. Reticulated platelet values in normal and thrombocytopenic neonates. J Pediatr 1996;129:269–74.CrossRefGoogle ScholarPubMed
Saxonhouse, MA, Sola, MC, Pastos, KM, et al. Reticulated platelet percentages in term and preterm neonates. J Pediatr Hematol Oncol 2004;26:797–802.Google ScholarPubMed
Jilma-Stohlawetz, P, Homoncik, M, Jilma, B, et al. High levels of reticulated platelets and thrombopoietin characterize fetal thrombopoiesis. Br J Haematol 2001;112:466–8.CrossRefGoogle ScholarPubMed
Briggs, C, Kunka, S, Hart, D, et al. Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia. Br J Haematol 2004;126:93–9.CrossRefGoogle Scholar
Cremer, M, Paetzold, J, Schmalisch, G, et al. Immature platelet fraction as novel laboratory parameter predicting the course of neonatal thrombocytopenia. Br J Haematol 2009;144:619–21.CrossRefGoogle ScholarPubMed
McDonald, TP, Cottrell, MB, Steward, SA, et al. Comparison of platelet production in two strains of mice with different modal megakaryocyte DNA ploidies after exposure to hypoxia. Exp Hematol 1992;20:51–6.Google ScholarPubMed
Meberg, A. Transitory thrombocytopenia in newborn mice after intrauterine hypoxia. Pediatr Res 1980;14:1071–3.CrossRefGoogle ScholarPubMed
Ohls, RK, Ehrenkranz, RA, Wright, LL, et al. Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial. Pediatrics 2001;108:934–42.CrossRefGoogle ScholarPubMed
Guida, JD, Kunig, AM, Leef, KH, et al. Platelet count and sepsis in very low birth weight neonates: is there an organism-specific response?Pediatrics 2003;111:1411–15.CrossRefGoogle ScholarPubMed
Manzoni, P, Mostert, M, Galletto, P, et al. Is thrombocytopenia suggestive of organism-specific response in neonatal sepsis?Pediatr Int 2009;51:206–10.CrossRefGoogle ScholarPubMed
Murray, NA, Howarth, LJ, McCloy, MP, et al. Platelet transfusion in the management of severe thrombocytopenia in neonatal intensive care unit patients. Transfus Med 2002;12:35–41.CrossRefGoogle ScholarPubMed
Modanlou, HD, Ortiz, OB. Thrombocytopenia in neonatal infection. Clin Pediatr (Phila) 1981;20:402–7.CrossRefGoogle ScholarPubMed
Dohner, ML, Wiedmeier, SE, Stoddard, RA, et al. Very high users of platelet transfusions in the neonatal intensive care unit. Transfusion 2009;49:869–72.CrossRefGoogle ScholarPubMed
Harker, LA, Slichter, SJ. Platelet and fibrinogen consumption in man. N Engl J Med 1972;287:999–1005.CrossRefGoogle ScholarPubMed
Tate, DY, Carlton, GT, Johnson, D, et al. Immune thrombocytopenia in severe neonatal infections. J Pediatr 1981;98:449–53.CrossRefGoogle ScholarPubMed
Brown, RE, Rimsza, LM, Pastos, K, et al. Effects of sepsis on neonatal thrombopoiesis. Pediatr Res 2008;64:399–404.CrossRefGoogle ScholarPubMed
Steinberg, HN, Anderson, J, Jr., Lim, B, et al. Cytomegalovirus infection of the BS-1 human stroma cell line: effect on murine hemopoiesis. Virology 1993;196:427–32.CrossRefGoogle ScholarPubMed
Crapnell, K, Zanjani, ED, Chaudhuri, A, et al. In vitro infection of megakaryocytes and their precursors by human cytomegalovirus. Blood 2000;95:487–93.Google ScholarPubMed
Isomura, H, Yoshida, M, Namba, H, et al. Interaction of human herpesvirus 6 with human CD34 positive cells. J Med Virol 2003;70:444–50.CrossRefGoogle ScholarPubMed
Srivastava, A, Bruno, E, Briddell, R, et al. Parvovirus B19-induced perturbation of human megakaryocytopoiesis in vitro. Blood 1990;76:1997–2004.Google ScholarPubMed
Forestier, F, Tissot, JD, Vial, Y, et al. Haematological parameters of parvovirus B19 infection in 13 fetuses with hydrops foetalis. Br J Haematol 1999;104:925–7.CrossRefGoogle ScholarPubMed
Abzug, MJ. Prognosis for neonates with enterovirus hepatitis and coagulopathy. Pediatr Infect Dis J 2001;20:758–63.CrossRefGoogle ScholarPubMed
Hutter, JJ, Jr., Hathaway, WE, Wayne, ER. Hematologic abnormalities in severe neonatal necrotizing enterocolitis. J Pediatr 1976;88:1026–31.CrossRefGoogle ScholarPubMed
Ververidis, M, Kiely, EM, Spitz, L, et al. The clinical significance of thrombocytopenia in neonates with necrotizing enterocolitis. J Pediatr Surg 2001;36:799–803.CrossRefGoogle ScholarPubMed
Frost, BL, Jilling, T, Caplan, MS. The importance of pro-inflammatory signaling in neonatal necrotizing enterocolitis. Semin Perinatol 2008;32:100–6.CrossRefGoogle ScholarPubMed
Caplan, MS, Hedlund, E, Adler, L, et al. The platelet-activating factor receptor antagonist WEB 2170 prevents neonatal necrotizing enterocolitis in rats. J Pediatr Gastroenterol Nutr 1997;24:296–301.CrossRefGoogle ScholarPubMed
Ropert, JC, Dreyfus, M, Dehan, M, et al. [Severe neonatal thrombocytopenia. Analysis of the etiologic data on 64 cases]. Arch Fr Pediatr 1984;41:85–90.Google Scholar
Castle, V, Coates, G, Mitchell, LG, et al. The effect of hypoxia on platelet survival and site of sequestration in the newborn rabbit. Thromb Haemost 1988;59:45–8.Google ScholarPubMed
Hoffmeister, KM, Felbinger, TW, Falet, H, et al. The clearance mechanism of chilled blood platelets. Cell 2003;112:87–97.CrossRefGoogle ScholarPubMed
Marks, SD, Massicotte, MP, Steele, BT, et al. Neonatal renal venous thrombosis: clinical outcomes and prevalence of prothrombotic disorders. J Pediatr 2005;146:811–16.CrossRefGoogle ScholarPubMed
Zigman, A, Yazbeck, S, Emil, S, et al. Renal vein thrombosis: a 10-year review. J Pediatr Surg 2000;35:1540–2.CrossRefGoogle ScholarPubMed
Enjolras, O, Wassef, M, Mazoyer, E, et al. Infants with Kasabach–Merritt syndrome do not have “true” hemangiomas. J Pediatr 1997;130:631–40.CrossRefGoogle ScholarPubMed
Aster, RH, Bougie, DW. Drug-induced immune thrombocytopenia. N Engl J Med 2007;357:580–7.CrossRefGoogle ScholarPubMed
Spadone, D, Clark, F, James, E, et al. Heparin-induced thrombocytopenia in the newborn. J Vasc Surg 1992;15:306–11; discussion 11–12.CrossRefGoogle ScholarPubMed
Klenner, AF, Fusch, C, Rakow, A, et al. Benefit and risk of heparin for maintaining peripheral venous catheters in neonates: a placebo-controlled trial. J Pediatr 2003;143:741–5.CrossRefGoogle ScholarPubMed
Risch, L, Huber, AR, Schmugge, M. Diagnosis and treatment of heparin-induced thrombocytopenia in neonates and children. Thromb Res 2006;118:123–35.CrossRefGoogle ScholarPubMed
Nguyen, TN, Gal, P, Ransom, JL, et al. Lepirudin use in a neonate with heparin-induced thrombocytopenia. Ann Pharmacother 2003;37:229–33.CrossRefGoogle Scholar
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;41:803–8.CrossRefGoogle Scholar
Garcia, MG, Duenas, E, Sola, MC, et al. Epidemiologic and outcome studies of patients who received platelet transfusions in the neonatal intensive care unit. J Perinatol 2001;21:415–20.CrossRefGoogle ScholarPubMed
Israels, SJ, Odaibo, FS, Robertson, C, et al. Deficient thromboxane synthesis and response in platelets from premature infants. Pediatr Res 1997;41:218–23.CrossRefGoogle ScholarPubMed
Rajasekhar, D, Kestin, AS, Bednarek, FJ, et al. Neonatal platelets are less reactive than adult platelets to physiological agonists in whole blood. Thromb Haemost 1994;72:957–63.Google ScholarPubMed
Andrew, M, Castle, V, Mitchell, L, et al. Modified bleeding time in the infant. Am J Hematol 1989;30:190–1.CrossRefGoogle ScholarPubMed
Boudewijns, M, Raes, M, Peeters, V, et al. Evaluation of platelet function on cord blood in 80 healthy term neonates using the Platelet Function Analyser (PFA-100); shorter in vitro bleeding times in neonates than adults. Eur J Pediatr 2003;162:212–13.CrossRefGoogle ScholarPubMed
Israels, SJ, Cheang, T, McMillan-Ward, EM, et al. Evaluation of primary hemostasis in neonates with a new in vitro platelet function analyzer. J Pediatr 2001;138:116–19.CrossRefGoogle ScholarPubMed
Roschitz, B, Sudi, K, Kostenberger, M, et al. Shorter PFA-100 closure times in neonates than in adults: role of red cells, white cells, platelets and von Willebrand factor. Acta Paediatr 2001;90:664–70.CrossRefGoogle ScholarPubMed
Del Vecchio, A, Latini, G, Henry, E, et al. Template bleeding times of 240 neonates born at 24 to 41 weeks gestation. J Perinatol 2008;28:427–31.CrossRefGoogle ScholarPubMed
Bednarek, FJ, Bean, S, Barnard, MR, et al. The platelet hyporeactivity of extremely low birth weight neonates is age-dependent. Thromb Res 2009;124:42–5.CrossRefGoogle ScholarPubMed
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;123:278–85.CrossRefGoogle ScholarPubMed
Kahn, DJ, Richardson, DK, Billett, HH. Inter-NICU variation in rates and management of thrombocytopenia among very low birth-weight infants. J Perinatol 2003;23:312–16.CrossRefGoogle ScholarPubMed
Andrew, M, Vegh, P, Caco, C, et al. A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants. J Pediatr 1993;123:285–91.CrossRefGoogle ScholarPubMed
Stanworth, SJ, Clarke, P, Watts, T, et al. Prospective, observational study of outcomes in neonates with severe thrombocytopenia. Pediatrics 2009;124:e826–34.CrossRefGoogle ScholarPubMed
Goldman, M, Webert, KE, Arnold, DM, et al. Proceedings of a consensus conference: towards an understanding of TRALI. Transfus Med Rev 2005;19:2–31.CrossRefGoogle ScholarPubMed
Fatal bacterial infections associated with platelet transfusions – United States, 2004. MMWR 2005;54:168–70.
Baer, VL, Lambert, DK, Henry, E, et al. Do platelet transfusions in the NICU adversely affect survival? Analysis of 1600 thrombocytopenic neonates in a multihospital healthcare system. J Perinatol 2007;27:790–6.CrossRefGoogle Scholar
Bonifacio, L, Petrova, A, Nanjundaswamy, S, et al. Thrombocytopenia related neonatal outcome in preterms. Indian J Pediatr 2007;74:269–74.CrossRefGoogle ScholarPubMed
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;25:173–7.CrossRefGoogle Scholar
Bussel, JB, Mukherjee, R, Stone, AJ. A pilot study of rhuIL-11 treatment of refractory ITP. Am J Hematol 2001;66:172–7.3.0.CO;2-Q>CrossRefGoogle ScholarPubMed
Kuter, DJ. Thrombopoietin and thrombopoietin mimetics in the treatment of thrombocytopenia. Ann Rev Med 2009;60:193–206.CrossRefGoogle ScholarPubMed
Bussel, JB, Cheng, G, Saleh, MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007;357:2237–47.CrossRefGoogle ScholarPubMed
Bussel, JB, Kuter, DJ, George, JN, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med 2006;355:1672–81.CrossRefGoogle ScholarPubMed
Pastos, KM, Slayton, WB, Rimsza, LM, et al. Differential effects of recombinant thrombopoietin and bone marrow stromal-conditioned media on neonatal versus adult megakaryocytes. Blood 2006;108:3360–2.CrossRefGoogle ScholarPubMed
Sola, MC, Christensen, RD, Hutson, AD, et al. Pharmacokinetics, pharmacodynamics, and safety of administering pegylated recombinant megakaryocyte growth and development factor to newborn rhesus monkeys. Pediatr Res 2000;47:208–14.CrossRefGoogle ScholarPubMed
Sola, MC, Du, Y, Hutson, AD, et al. Dose-response relationship of megakaryocyte progenitors from the bone marrow of thrombocytopenic and non-thrombocytopenic neonates to recombinant thrombopoietin. Br J Haematol 2000;110:449–53.CrossRefGoogle ScholarPubMed

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