Perinatal Hematology

  • John Kim ChoiEmail author
  • Jeremie Heath Estepp


The perinatal period is one of rapid physiological change and evolution, challenging the clinical practitioner to differentiate between normal variation and a pathologic state. Correct interpretation of hematological abnormalities is dependent on accounting for maternal and fetal influences, including maternal pathology, genetic predisposition, and pathologic maternal-fetal interaction. These hematological problems are almost universal in premature and sick neonates but can occur unexpectedly in otherwise healthy term babies. In either case, these diagnoses often require immediate management. Quantitative tests on peripheral blood and bone marrow aspirates/biopsy including morphological analysis require care in collection and processing to reduce artefact and variability; they require experience and expertise in interpretation as values and morphology are highly age dependent. In this chapter, we review some pathologic states that can present in neonates due to bleeding, toxin exposure, and maternal pathology during pregnancy. Additionally, we will discuss conditions that present following delivery, such as coagulopathies, cytopenias, and leukemias.


Hematology Coagulopathy Anemia Neutropenia Thrombocytopenia Cytopenia Bone marrow failure Transient abnormal myelopoiesis Leukemoid reaction Congenital leukemia 


  1. 1.
    Cross JC. Placental function in development and disease. Reprod Fertil Dev. 2006;18:71–6.PubMedGoogle Scholar
  2. 2.
    West JR, Blake CA. Fetal alcohol syndrome: an assessment of the field. Exp Biol Med (Maywood). 2005;230:354–6.Google Scholar
  3. 3.
    Sharpe CR, Franco EL. Use of dipyrone during pregnancy and risk of Wilms’ tumor. Brazilian Wilms’ Tumor Study Group. Epidemiology. 1996;7:533–5.PubMedGoogle Scholar
  4. 4.
    Alexander FE, Patheal SL, Biondi A, Brandalise S, Cabrera ME, Chan LC, et al. Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion. Cancer Res. 2001;61:2542–6.Google Scholar
  5. 5.
    Thompson JR, Gerald PF, Willoughby ML, Armstrong BK. Maternal folate supplementation in pregnancy and protection against acute lymphoblastic leukaemia in childhood: a case-control study. Lancet. 2001;358:1935–40.Google Scholar
  6. 6.
    Wardrop CA, Holland BM. The roles and vital importance of placental blood to the newborn infant. J Perinat Med. 1995;23:139–43.PubMedGoogle Scholar
  7. 7.
    Holton ME. Unexpected anemia in a newborn. Tex Med. 1989;85:50–1.Google Scholar
  8. 8.
    Arcasoy MO, Gallagher PG. Hematologic disorders and nonimmune hydrops fetalis. Semin Perinatol. 1995;19:502–15.Google Scholar
  9. 9.
    Sebring ES, Polesky HF. Fetomaternal hemorrhage: incidence, risk factors, time of occurrence, and clinical effects. Transfusion. 1990;30:344–57.PubMedGoogle Scholar
  10. 10.
    Biankin SA, Arbuckle SM, Graf NS. Autopsy findings in a series of five cases of fetomaternal haemorrhages. Pathology. 2003;35:319–24.PubMedGoogle Scholar
  11. 11.
    Kleihauer E, Braun H, Betke K. Demonstration of fetal hemoglobin in erythrocytes of a blood smear. Klin Wochenschr. 1957;35:637–8.PubMedGoogle Scholar
  12. 12.
    Kelsey P, Reilly JT, Chapman JF, Bain BJ, Bates SC, Knowles SM, et al. The estimation of fetomaternal haemorrhage. Transfus Med. 1999;9:87–92.Google Scholar
  13. 13.
    Muench MV, Baschat AA, Reddy UM, Mighty HE, Weiner CP, Scalea TM, et al. Kleihauer-betke testing is important in all cases of maternal trauma. J Trauma. 2004;57:1094–8.PubMedGoogle Scholar
  14. 14.
    Pelikan DM, Mesker WE, Scherjon SA, Kanhai HH, Tanke HJ. Improvement of the Kleihauer-Betke test by automated detection of fetal erythrocytes in maternal blood. Cytometry B Clin Cytom. 2003;54:1–9.Google Scholar
  15. 15.
    Pelikan DM, Scherjon SA, Mesker WE, de Groot-Swings GM, Brouwer-Mandema GG, Tanke HJ, et al. Quantification of fetomaternal hemorrhage: a comparative study of the manual and automated microscopic Kleihauer-Betke tests and flow cytometry in clinical samples. Am J Obstet Gynecol. 2004;191:551–7.PubMedGoogle Scholar
  16. 16.
    Nelson M. An overview of the use of flow cytometry in the analysis of mixed red cell populations. Pathology. 1999;31:191–8.PubMedGoogle Scholar
  17. 17.
    Oyelese KO, Turner M, Lees C, Campbell S. Vasa previa: an avoidable obstetric tragedy. Obstet Gynecol Surv. 1999;54:138–45.PubMedGoogle Scholar
  18. 18.
    Akhter MS, Savior JF, Akhter IA, Deacon JS. Fetal exsanguination associated with antepartum hemorrhage. Can Med Assoc J. 1978;118:651–2, 657.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Cordero L, Franco A, Joy SD. Monochorionic monoamniotic twins: neonatal outcome. J Perinatol. 2006;26:170–5.PubMedGoogle Scholar
  20. 20.
    Lim YK, Tan TY, Zuzarte R, Daniel ML, Yeo GS. Outcomes of twin-twin transfusion syndrome managed by a specialised twin clinic. Singapore Med J. 2005;46:401–6.PubMedGoogle Scholar
  21. 21.
    Rodeck CH, Weisz B, Peebles DM, Jauniaux E. Hypothesis: the placental ‘steal’ phenomenon – a possible hazard of amnioreduction. Fetal Diagn Ther. 2006;21:302–6.PubMedGoogle Scholar
  22. 22.
    Wenstrom KD, Tessen JA, Zlatnik FJ, Sipes SL. Frequency, distribution, and theoretical mechanisms of hematologic and weight discordance in monochorionic twins. Obstet Gynecol. 1992;80:257–61.Google Scholar
  23. 23.
    Cordero L, Franco A, Joy SD, O’Shaughnessy RW. Monochorionic diamniotic infants without twin-to-twin transfusion syndrome. J Perinatol. 2005;25:753–8.PubMedGoogle Scholar
  24. 24.
    Blickstein I. The twin-twin transfusion syndrome. Obstet Gynecol. 1990;76:714–22.PubMedGoogle Scholar
  25. 25.
    Lewi L, Van Schoubroeck D, Gratacos E, Witters I, Timmerman D, Deprest J. Monochorionic diamniotic twins: complications and management options. Curr Opin Obstet Gynecol. 2003;15:177–94.PubMedGoogle Scholar
  26. 26.
    Duncan KR. Twin-to-twin transfusion: update on management options and outcomes. Curr Opin Obstet Gynecol. 2005;17:618–22.PubMedGoogle Scholar
  27. 27.
    Akkermans J, Peeters SH, Klumper FJ, Middeldorp JM, Lopriore E, Oepkes D. Is the sequential laser technique for twin-to-twin transfusion syndrome truly superior to the standard selective technique? A meta-analysis. Fetal Diagn Ther. 2015;37:251–8.PubMedGoogle Scholar
  28. 28.
    Yamamoto M, Ville Y. Recent findings on laser treatment of twin-to-twin transfusion syndrome. Curr Opin Obstet Gynecol. 2006;18:87–92.PubMedGoogle Scholar
  29. 29.
    Lopriore E, Sueters M, Middeldorp JM, Oepkes D, Vandenbussche FP, Walther FJ. Neonatal outcome in twin-to-twin transfusion syndrome treated with fetoscopic laser occlusion of vascular anastomoses. J Pediatr. 2005;147:597–602.PubMedGoogle Scholar
  30. 30.
    Roberts D, Neilson JP, Kilby MD, Gates S. Interventions for the treatment of twin-twin transfusion syndrome. Cochrane Database Syst Rev. 2014;1:CD002073.Google Scholar
  31. 31.
    Rossi AC, Vanderbilt D, Chmait RH. Neurodevelopmental outcomes after laser therapy for twin-twin transfusion syndrome: a systematic review and meta-analysis. Obstet Gynecol. 2011;118:1145–50.Google Scholar
  32. 32.
    Schmidt WA, Affleck JA, Jacobson SL. Fatal fetal hemorrhage and placental pathology. Report of three cases and a new setting. Placenta. 2005;26:419–31.PubMedGoogle Scholar
  33. 33.
    Gebremariam A. Subgaleal haemorrhage: risk factors and neurological and developmental outcome in survivors. Ann Trop Paediatr. 1999;19:45–50.Google Scholar
  34. 34.
    Kilani RA, Wetmore J. Neonatal subgaleal hematoma: presentation and outcome–radiological findings and factors associated with mortality. Am J Perinatol. 2006;23:41–8.Google Scholar
  35. 35.
    Doumouchtsis SK, Arulkumaran S. Head injuries after instrumental vaginal deliveries. Curr Opin Obstet Gynecol. 2006;18:129–34.PubMedGoogle Scholar
  36. 36.
    Lin JC, Strauss RG, Kulhavy JC, Johnson KJ, Zimmerman MB, Cress GA, et al. Phlebotomy overdraw in the neonatal intensive care nursery. Pediatrics. 2000;106:E19.PubMedGoogle Scholar
  37. 37.
    Fayyad AM, Harrington KF. Prediction and prevention of preeclampsia and IUGR. Early Hum Dev. 2005;81:865–76.PubMedGoogle Scholar
  38. 38.
    Duley L, Meher S, Abalos E. Management of pre-eclampsia. BMJ. 2006;332:463–8.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Tamakoshi K, Yatsuya H, Wada K, Matsushita K, Otsuka R, Yang PO, et al. Birth weight and adult hypertension: cross-sectional study in a Japanese workplace population. Circ J. 2006;70:262–7.PubMedGoogle Scholar
  40. 40.
    Mugo M, Govindarajan G, Kurukulasuriya LR, Sowers JR, McFarlane SI. Hypertension in pregnancy. Curr Hypertens Rep. 2005;7:348–54.PubMedGoogle Scholar
  41. 41.
    Reece EA, Leguizamon G, Homko C. Pregnancy performance and outcomes associated with diabetic nephropathy. Am J Perinatol. 1998;15:413–21.PubMedGoogle Scholar
  42. 42.
    Maulik D. Fetal growth restriction and macrosomia: an apparently intriguing combination. J Matern Fetal Neonatal Med. 2003;13:145–6.PubMedGoogle Scholar
  43. 43.
    Lampl M, Jeanty P. Exposure to maternal diabetes is associated with altered fetal growth patterns: a hypothesis regarding metabolic allocation to growth under hyperglycemic-hypoxemic conditions. Am J Hum Biol. 2004;16:237–63.PubMedGoogle Scholar
  44. 44.
    Jaffe R. Identification of fetal growth abnormalities in diabetes mellitus. Semin Perinatol. 2002;26:190–5.PubMedGoogle Scholar
  45. 45.
    Trevisan G, Ramos JG, Martins-Costa S, Barros EJ. Pregnancy in patients with chronic renal insufficiency at Hospital de Clínicas of Porto Alegre, Brazil. Ren Fail. 2004;26:29–34.PubMedGoogle Scholar
  46. 46.
    Ashfaq M, Janjua MZ, Nawaz M. Effects of maternal smoking on placental morphology. J Ayub Med Coll Abbottabad. 2003;15:12–5.PubMedGoogle Scholar
  47. 47.
    Vogt IC. Maternal smoking, intrauterine growth restriction, and placental apoptosis. Pediatr Dev Pathol. 2004;7:433–42.Google Scholar
  48. 48.
    Bada HS, Das A, Bauer CR, Shankaran S, Lester BM, Gard CC, et al. Low birth weight and preterm births: etiologic fraction attributable to prenatal drug exposure. J Perinatol. 2005;25:631–7.PubMedGoogle Scholar
  49. 49.
    Zdravkovic T, Genbacev O, McMaster MT, Fisher SJ. The adverse effects of maternal smoking on the human placenta: a review. Placenta. 2005;26:S81–6.PubMedGoogle Scholar
  50. 50.
    Watts T, Roberts I. Haematological abnormalities in the growth-restricted infant. Semin Neonatol. 1999;4:41–54.Google Scholar
  51. 51.
    Koenig JM, Christensen RD. Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med. 1989;321:557–62.PubMedGoogle Scholar
  52. 52.
    Murray NA, Roberts IA. Circulating megakaryocytes and their progenitors in early thrombocytopenia in preterm neonates. Pediatr Res. 1996;40:112–9.PubMedGoogle Scholar
  53. 53.
    Murray N. New concepts in the aetiology and management of neonatal thrombocytopenia. Semin Neonatol. 1999;4:27–40.Google Scholar
  54. 54.
    Perrine SP, Greene MF, Lee PD, Cohen RA, Faller DV. Insulin stimulates cord blood erythroid progenitor growth: evidence for an aetiological role in neonatal polycythaemia. Br J Haematol. 1986;64:503–11.PubMedGoogle Scholar
  55. 55.
    McIntosh N, Kempson C, Tyler RM. Blood counts in extremely low birthweight infants. Arch Dis Child. 1988;63:74–6.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Christensen RD, Liechty KW, Koenig JM, Schibler KR, Ohls RK. Administration of erythropoietin to newborn rats results in diminished neutrophil production. Blood. 1991;78:1241–6.PubMedGoogle Scholar
  57. 57.
    Christensen RD, Koenig JM, Viskochil DH, Rothstein G. Down-modulation of neutrophil production by erythropoietin in human hematopoietic clones. Blood. 1989;74:817–22.PubMedGoogle Scholar
  58. 58.
    Koenig JM, Christensen RD. The mechanism responsible for diminished neutrophil production in neonates delivered of women with pregnancy-induced hypertension. Am J Obstet Gynecol. 1991;165:467–73.PubMedGoogle Scholar
  59. 59.
    Chirico G, Ciardelli L, Cecchi P, De Amici M, Gasparoni A, Rondini G. Serum concentration of granulocyte colony stimulating factor in term and preterm infants. Eur J Pediatr. 1997;156:269–71.PubMedGoogle Scholar
  60. 60.
    Rondini G, Chirico G. Hematopoietic growth factor levels in term and preterm infants. Curr Opin Hematol. 1999;6:192–7.PubMedGoogle Scholar
  61. 61.
    Paul D, Leef K, Taylor S, McKenzie S. Thrombopoietin in preterm infants: gestational age-dependent response. J Pediatr Hematol Oncol. 2002;24:304–9.PubMedGoogle Scholar
  62. 62.
    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.PubMedGoogle Scholar
  63. 63.
    Watts T, Murray N, Roberts I. Thrombopoietin has a primary role in the regulation of platelet production in preterm babies. Pediatr Res. 1999;46:28–32.PubMedGoogle Scholar
  64. 64.
    Tenovuo A. Neonatal complications in small-for-gestational age neonates. J Perinat Med. 1988;16:197–203.PubMedGoogle Scholar
  65. 65.
    Merchant RH, Phadke SD, Sakhalkar VS, Agashe VS, Puniyani RR. Hematocrit and whole blood viscosity in newborns: analysis of 100 cases. Indian Pediatr. 1992;29:555–61.PubMedGoogle Scholar
  66. 66.
    Werner E. Neonatal polycythaemia and hyperviscosity. Clin Perinatol. 1995;22:693–710.PubMedGoogle Scholar
  67. 67.
    Wong W, Fok TF, Lee CH, Ng PC, So KW, Ou Y, et al. Randomised controlled trial: comparison of colloid or crystalloid for partial exchange transfusion for treatment of neonatal polycythaemia. Arch Dis Child Fetal Neonatal Ed. 1997;77:F115–8.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Carr R, Modi N, Dore C. G-csf and gm-csf for treating or preventing neonatal infections. Cochrane Database Syst Rev. 2003;(3):CD003066.Google Scholar
  69. 69.
    Sola-Visner M, Saxonhouse MA, Brown RE. Neonatal thrombocytopenia: what we do and don’t know. Early Hum Dev. 2008;84:499–506. PubMedGoogle Scholar
  70. 70.
    Blanchette VS, Kuhne T, Hume H, Hellmann J. Platelet transfusion therapy in newborn infants. Transfus Med Rev. 1995;9:215–30.PubMedGoogle Scholar
  71. 71.
    Andrew M, Vegh P, Caco C, Kirpalani H, Jefferies A, Ohlsson A, et al. A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants. J Pediatr. 1993;123:285–91.PubMedGoogle Scholar
  72. 72.
    Andrew M, Castle V, Saigal S, Carter C, Kelton JG. Clinical impact of neonatal thrombocytopenia. J Pediatr. 1987;110:457–64.PubMedGoogle Scholar
  73. 73.
    Fantoli U. Anti-D gamma globulins in the prevention of hemolytic disease of the newborn. Recenti Prog Med. 1966;40:371–2.Google Scholar
  74. 74.
    Clarke CA. Prevention of Rh-haemolytic disease. Br Med J. 1967;4:7–12.Google Scholar
  75. 75.
    Anonymous. Royal College of Physicians of Edinburgh/Royal College of Obstetricians and Gynaecologists Consensus Conference on anti-D prophylaxis, 7-8 April 1997. Br J Haematol. 1997;97:927–8.Google Scholar
  76. 76.
    Crowther CA, Keirse MJ. Anti-D administration in pregnancy for preventing rhesus alloimmunisation. Cochrane Database Syst Rev. 2000;(2):CD000020.Google Scholar
  77. 77.
    van Dijk BA, Dooren MC, Overbeeke MA. Red cell antibodies in pregnancy: there is no ‘critical titre’. Transfus Med. 1995;5:199–202.PubMedGoogle Scholar
  78. 78.
    Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. 2004;364:1343–60.PubMedGoogle Scholar
  79. 79.
    Scaradavou A, Inglis S, Peterson P, Dunne J, Chervenak F, Bussel J. Suppression of erythropoiesis by intrauterine transfusions in hemolytic disease of the newborn: use of erythropoietin to treat the late anemia. J Pediatr. 1993;123:279–84.PubMedGoogle Scholar
  80. 80.
    Mayne KM, Bowell PJ, Pratt GA. The significance of anti-kell sensitization in pregnancy. Clin Lab Haematol. 1990;12:379–85.PubMedGoogle Scholar
  81. 81.
    Vaughan JI, Warwick R, Letsky E, Nicolini U, Rodeck CH, Fisk NM. Erythropoietic suppression in fetal anemia because of kell alloimmunization. Am J Obstet Gynecol. 1994;171:247–52.PubMedGoogle Scholar
  82. 82.
    Mari G, Deter RL, Carpenter RL, Rahman F, Zimmerman R, Moise Jr KJ, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. N Engl J Med. 2000;342:9–14.PubMedGoogle Scholar
  83. 83.
    Kaplan C, Morel-Kopp MC, Clemenceau S, Daffos F, Forestier F, Tchernia G. Fetal and neonatal alloimmune thrombocytopenia: current trends in diagnosis and therapy. Transfus Med. 1992;2:265–71.PubMedGoogle Scholar
  84. 84.
    Uhrynowska M, Niznikowska-Marks M, Zupanska B. Neonatal and maternal thrombocytopenia: incidence and immune background. Eur J Haematol. 2000;64:42–6.PubMedGoogle Scholar
  85. 85.
    Turner ML, Bessos H, Fagge T, Harkness M, Rentoul F, Seymour J, et al. Prospective epidemiologic study of the outcome and cost-effectiveness of antenatal screening to detect neonatal alloimmune thrombocytopenia due to anti-HPA-1a. Transfusion. 2005;45:1945–56.PubMedGoogle Scholar
  86. 86.
    Bessos H, Seghatchian J. What’s happening? The expanding role of apheresis platelet support in neonatal alloimmune thrombocytopenia: current status and future trends. Transfus Apher Sci. 2005;33:191–7.PubMedGoogle Scholar
  87. 87.
    Campbell-Lee SA, DeSantis-Parsons D, Shirey RS, Kickler TS. Neonatal alloimmune thrombocytopenia due to anti-HPA-5b (Bra). Immunohematology. 2003;19:127–31.Google Scholar
  88. 88.
    Han KS, Song EY, Park MH. Neonatal alloimmune thrombocytopenia due to HLA antibodies. Int J Hematol. 2002;76:361–3.PubMedGoogle Scholar
  89. 89.
    Ertel K, Al-Tawil M, Santoso S, Kroll H. Relevance of the HPA-15 (Gov) polymorphism on CD109 in alloimmune thrombocytopenic syndromes. Transfusion. 2005;45:366–73.PubMedGoogle Scholar
  90. 90.
    Panzer S, Auerbach L, Cechova E, Fischer G, Holensteiner A, Kitl EM, et al. Maternal alloimmunization against fetal platelet antigens: a prospective study. Br J Haematol. 1995;90:655–60.PubMedGoogle Scholar
  91. 91.
    Mandelbaum M, Koren D, Eichelberger B, Auerbach L, Panzer S. Frequencies of maternal platelet alloantibodies and autoantibodies in suspected fetal/neonatal alloimmune thrombocytopenia, with emphasis on human platelet antigen-15 alloimmunization. Vox Sang. 2005;89:39–43.PubMedGoogle Scholar
  92. 92.
    Thude H, Schorner U, Helfricht C, Loth M, Maak B, Barz D. Neonatal alloimmune thrombocytopenia caused by human leucocyte antigen-B27 antibody. Transfus Med. 2006;16:143–9.PubMedGoogle Scholar
  93. 93.
    Grainger JD, Morrell G, Yates J, Deleacy D. Neonatal alloimmune thrombocytopenia with significant HLA antibodies. Arch Dis Child Fetal Neonatal Ed. 2002;86:F200–1.Google Scholar
  94. 94.
    Johnson JA, Ryan G, al-Musa A, Farkas S, Blanchette VS. Prenatal diagnosis and management of neonatal alloimmune thrombocytopenia. Semin Perinatol. 1997;21:45–52.PubMedGoogle Scholar
  95. 95.
    Sukati H, Bessos H, Barker RN, Urbaniak SJ. Characterization of the alloreactive helper t-cell response to the platelet membrane glycoprotein IIIa (integrin-beta3) in human platelet antigen-1a alloimmunized human platelet antigen-1b1b women. Transfusion. 2005;45:1165–77.PubMedGoogle Scholar
  96. 96.
    Bessos H, Perez S, Armstrong-Fisher S, Urbaniak S, Turner M. The development of a quantitative elisa for antibodies against human platelet antigen type 1a. Transfusion. 2003;43:350–6.PubMedGoogle Scholar
  97. 97.
    Beadling WV, Herman JH, Stuart MJ, Keashen-Schnell M, Miller JL. Fetal bleeding in neonatal alloimmune thrombocytopenia mediated by anti-PlAl is not associated with inhibition of fibrinogen binding to platelet GPIIb/IIIa. Am J Clin Pathol. 1995;103:636–41.PubMedGoogle Scholar
  98. 98.
    Bessos H, Turner M, Urbaniak SJ. Is there a relationship between anti-HPA-1a concentration and severity of neonatal alloimmune thrombocytopenia? Immunohematology. 2005;21:102–9.Google Scholar
  99. 99.
    Kaplan C, Daffos F, Forestier F, Cox WL, Lyon-Caen D, Dupuy-Montbrun MC, et al. Management of alloimmune thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets. Blood. 1988;72:340–3.PubMedGoogle Scholar
  100. 100.
    Jaegtvik S, Husebekk A, Aune B, Oian P, Dahl LB, Skogen B. Neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies; the level of maternal antibodies predicts the severity of thrombocytopenia in the newborn. BJOG. 2000;107:691–4.Google Scholar
  101. 101.
    Williamson LM, Hackett G, Rennie J, Palmer CR, Maciver C, Hadfield R, et al. The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening. Blood. 1998;92:2280–7.Google Scholar
  102. 102.
    Lipitz S, Ryan G, Murphy MF, Robson SC, Haeusler MC, Metcalfe P, et al. Neonatal alloimmune thrombocytopenia due to anti-P1A1 (anti-HPA-1a): importance of paternal and fetal platelet typing for assessment of fetal risk. Prenat Diagn. 1992;12:955–8.PubMedGoogle Scholar
  103. 103.
    McQuilten ZK, Wood EM, Savoia H, Cole S. A review of pathophysiology and current treatment for neonatal alloimmune thrombocytopenia (NAIT) and introducing the Australian NAIT registry. Aust N Z J Obstet Gynaecol. 2011;51:191–8.PubMedGoogle Scholar
  104. 104.
    Anonymous. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120:574–96.Google Scholar
  105. 105.
    Bussel JB, Druzin ML, Cines DB, Samuels P. Thrombocytopenia in pregnancy. Lancet. 1991;337:251.PubMedGoogle Scholar
  106. 106.
    Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med. 1993;329:1463–6.PubMedGoogle Scholar
  107. 107.
    Fujimura K, Harada Y, Fujimoto T, Kuramoto A, Ikeda Y, Akatsuka J, et al. Nationwide study of idiopathic thrombocytopenic purpura in pregnant women and the clinical influence on neonates. Int J Hematol. 2002;75:426–33.PubMedGoogle Scholar
  108. 108.
    Burrows RF, Kelton JG. Low fetal risks in pregnancies associated with idiopathic thrombocytopenic purpura. Am J Obstet Gynecol. 1990;163:1147–50.PubMedGoogle Scholar
  109. 109.
    Burrows RF, Kelton JG. Thrombocytopenia during pregnancy. In: Greer I, Turpie A, Forbes C, editors. Haemostasis and thombosis in obstetrics and gynaecology. London: Chapman and Hall; 1992.Google Scholar
  110. 110.
    Burrows RF, Kelton JG. Alloimmune neonatal thrombocytopenia associated with incidental maternal thrombocytopenia. Am J Hematol. 1990;35:43–4.PubMedGoogle Scholar
  111. 111.
    Rosenblatt DS, Whitehead VM. Cobalamin and folate deficiency: acquired and hereditary disorders in children. Semin Hematol. 1999;36:19–34.PubMedGoogle Scholar
  112. 112.
    Hindmarsh PC, Geary MP, Rodeck CH, Jackson MR, Kingdom JC. Effect of early maternal iron stores on placental weight and structure. Lancet. 2000;356:719–23.PubMedGoogle Scholar
  113. 113.
    Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, et al. Development of the human coagulation system in the full-term infant. Blood. 1987;70:165–72. Google Scholar
  114. 114.
    Monagle P, Barnes C, Ignjatovic V, Furmedge J, Newall F, Chan A, et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost. 2006;95:362–72.PubMedGoogle Scholar
  115. 115.
    Williams MD, Chalmers EA, Gibson BE. The investigation and management of neonatal haemostasis and thrombosis. Br J Haematol. 2002;119:295–309.PubMedGoogle Scholar
  116. 116.
    Shearer MJ. Vitamin k. Lancet. 1995;345:229–34.Google Scholar
  117. 117.
    Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, et al. Development of the human coagulation system in the healthy premature infant. Blood. 1988;72:1651–7. Google Scholar
  118. 118.
    Fanaro S, Chierici R, Guerrini P, Vigi V. Intestinal microflora in early infancy: composition and development. Acta Paediatr. 2003;91:48–55.Google Scholar
  119. 119.
    Anonymous. Controversies concerning Vitamin K and the newborn. American Academy of Pediatrics Committee on Fetus and Newborn. Pediatrics. 2003;112:191–92.Google Scholar
  120. 120.
    Department of Health. Vitamin K for newborn babies. London: HMSO; 1998.Google Scholar
  121. 121.
    Delgado-Escueta AV, Janz D. Consensus guidelines: preconception counseling, management, and care of the pregnant woman with epilepsy. Neurology. 1992;42:149–60.PubMedGoogle Scholar
  122. 122.
    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;29:130–6.PubMedGoogle Scholar
  123. 123.
    George D, Bussel JB. Neonatal thrombocytopenia. Semin Thromb Hemost. 1995;21:276–93.PubMedGoogle Scholar
  124. 124.
    Enjolras O, Riche M, Merland J, Escande J. Management of alarming hemangiomas in infancy. A review of 25 cases. Pediatrics. 1990;85:491–8.PubMedGoogle Scholar
  125. 125.
    Ververidis M, Kiely EM, Spitz L, Drake DP, Eaton S, Pierro A. The clinical significance of thrombocytopenia in neonates with necrotizing enterocolitis. J Pediatr Surg. 2001;36:799–803.PubMedGoogle Scholar
  126. 126.
    Nowak-Gottl U, von Kries R, Gobel U. Neonatal symptomatic thromboembolism in Germany: two year survey. Arch Dis Child Fetal Neonatal Ed. 1997;76:F163–7.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry. Pediatrics. 1995;96:939–43.Google Scholar
  128. 128.
    Kadir RA. Women and inherited bleeding disorders: pregnancy and delivery. Semin Hematol. 1999;36:28–35.PubMedGoogle Scholar
  129. 129.
    Thomas A, Chalmers E. The neonate with hemophilia. In: Lee CA, Berntorp EE, Hoots WK, editors. Textbook of hemophilia. 1st ed. Oxford: Blackwells Publishing Ltd; 2005. p. 125–30.Google Scholar
  130. 130.
    Kulkarni R, Lusher J. Intracranial and extracranial haemorrhages in newborns with haemophilia: a review of the literature. J Pediatr Hematol Oncol. 1999;21:289–95.PubMedGoogle Scholar
  131. 131.
    Buchanan G. Factor concentrate prophylaxis for neonates with hemophilia. J Pediatr Hematol Oncol. 1999;21:254–5.PubMedGoogle Scholar
  132. 132.
    Lorenzo J, Lopez A, Aznar J. Incidence of inhibitors in severe haemophilia: the importance of patient age. Br J Haematol. 2001;113:600–3.PubMedGoogle Scholar
  133. 133.
    Van der Bom J, M-B EP, Fischer K. Age at first treatment and immune tolerance to factor viii in severe haemophilia. Blood Coagul Fibrinolysis. 2003;89:475–9.Google Scholar
  134. 134.
    Steiner LA, Gallagher PG. Erythrocyte disorders in the perinatal period. Semin Perinatol. 2007;31:254–61.PubMedPubMedCentralGoogle Scholar
  135. 135.
    Delaunay J. The molecular basis of hereditary red cell membrane disorders. Blood Rev. 2007;21:1–20.PubMedGoogle Scholar
  136. 136.
    Iolascon A, Heimpel H, Wahlin A, Tamary H. Congenital dyserythropoietic anemias: molecular insights and diagnostic approach. Blood. 2013;122:2162–6.PubMedPubMedCentralGoogle Scholar
  137. 137.
    Foucar K. Anemias. In: Foucar K, Reichard KK, Czuchlewski D, editors. Bone marrow pathology. 3rd ed. Chicago: ASCP Press; 2010. p. 93–129.Google Scholar
  138. 138.
    Bain BJ. Blood cells: a practical guide. 3rd ed. Oxford: Blackwell Science Ltd; 2002.Google Scholar
  139. 139.
    Hoffbrand AV, Pettit JE. Color atlas of clinical hematology. 3rd ed. London: Harcourt Publishers Limited; 2000.Google Scholar
  140. 140.
    Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB. Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet J Rare Dis. 2011;6:26.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Czuchlewski D. Neutropenia and agranulocytosis. In: Foucar K, Reichard KK, Czuchlewski D, editors. Bone marrow pathology. 3rd ed. Chicago: ASCP Press; 2010. p. 207–29.Google Scholar
  142. 142.
    Welte K, Zeidler C. Severe congenital neutropenia. Hematol Oncol Clin North Am. 2009;23:307–20.PubMedGoogle Scholar
  143. 143.
    Sera Y, Kawaguchi H, Nakamura K, Sato T, Habara M, Okada S, et al. A comparison of the defective granulopoiesis in childhood cyclic neutropenia and in severe congenital neutropenia. Haematologica. 2005;90:1032–41.PubMedGoogle Scholar
  144. 144.
    Balduini CL, Savoia A. Genetics of familial forms of thrombocytopenia. Hum Genet. 2012;131:1821–32.PubMedGoogle Scholar
  145. 145.
    Geddis AE. Inherited thrombocytopenias: an approach to diagnosis and management. Int J Lab Hematol. 2013;35:14–25.PubMedGoogle Scholar
  146. 146.
    Reichard KK. Megakaryocytic/platelet disorder. In: Foucar K, Reichard KK, Czuchlewski D, editors. Bone marrow pathology. Chicago: ASCP Press; 2010. p. 231–51.Google Scholar
  147. 147.
    Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D, et al. Haploinsufficiency of cbfa2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet. 1999;23:166–75.PubMedGoogle Scholar
  148. 148.
    Owen C, Barnett M, Fitzgibbon J. Familial myelodysplasia and acute myeloid leukaemia – a review. Br J Haematol. 2008;140:123–32.Google Scholar
  149. 149.
    Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G, et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia. 2003;17:277–82.PubMedGoogle Scholar
  150. 150.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC Press; 2008.Google Scholar
  151. 151.
    West AH, Godley LA, Churpek JE. Familial myelodysplastic syndrome/acute leukemia syndromes: a review and utility for translational investigations. Ann N Y Acad Sci. 2014;1310:111–8.PubMedPubMedCentralGoogle Scholar
  152. 152.
    Pasquet M, Bellanne-Chantelot C, Tavitian S, Prade N, Beaupain B, Larochelle O, et al. High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia. Blood. 2013;121:822–9.PubMedGoogle Scholar
  153. 153.
    Bresters D, Reus AC, Veerman AJ, van Wering ER, van der Does-van den Berg A, Kaspers GJ. Congenital leukaemia: the dutch experience and review of the literature. Br J Haematol. 2002;117:513–24.Google Scholar
  154. 154.
    Choi JK. Hematologic abnormalities in individuals with Down syndrome. In: Proytcheva M, editor. Diagnostic pediatric hematopathology. Cambridge: Cambridge University Press; 2011. p. 310–22.Google Scholar
  155. 155.
    Yoshida K, Toki T, Okuno Y, Kanezaki R, Shiraishi Y, Sato-Otsubo A, et al. The landscape of somatic mutations in Down syndrome-related myeloid disorders. Nat Genet. 2013;45:1293–9.PubMedGoogle Scholar

Copyright information

© Springer International Publishing 2015

Authors and Affiliations

  1. 1.Department of PathologySt. Jude Children’s Research HospitalMemphisUSA
  2. 2.Department of HematologySt. Jude Children’s Research HospitalMemphisUSA

Personalised recommendations