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Neonatal thrombocytopenia

INTRODUCTION

Although thrombocytopenia is relatively rare in the general newborn population, it occurs frequently in patients admitted to newborn intensive care units. The major mechanisms are either increased destruction or decreased production of platelets. Multiple causes may be involved in some cases.

Thrombocytopenia in the newborn is reviewed here. Evaluation of a child with a bleeding disorder is discussed separately. (See "Approach to the child with bleeding symptoms".)

DEFINITION

Historically, neonatal thrombocytopenia has been defined as a platelet count less than 150,000/microL based upon the definition used in adults, which corresponds to values at or below the 5th percentile. However, healthy preterm and term newborns have counts significantly below this level [1-3].

This was best illustrated from a study from the Intermountain Healthcare group that reviewed the platelet counts of 34,146 neonates (gestational age from 22 to 42 weeks) from the first three days of life [2]. In neonates, the 5th percentile was lower than the standard adult value of 150,000/microL and decreased with decreasing gestational age. For example, the 5th percentile was 104,200/microL for infants below 32 weeks gestation and was 123,100/microL for late preterm (34 to 36 weeks gestation) and term infants (gestational age greater than 37 weeks). Platelet counts increased with advancing postnatal age.

Severe reductions (platelet count <50,000/microL) and/or persistent thrombocytopenia can result in bleeding. Severe and/or persistent thrombocytopenia requires evaluation, even in an asymptomatic infant.

                                                 

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Literature review current through: Aug 2014. | This topic last updated: Aug 2, 2013.
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References
Top
  1. Sola MC, Del Vecchio A, Rimsza LM. Evaluation and treatment of thrombocytopenia in the neonatal intensive care unit. Clin Perinatol 2000; 27:655.
  2. 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.
  3. Andrew M, Kelton J. Neonatal thrombocytopenia. Clin Perinatol 1984; 11:359.
  4. Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med 1993; 329:1463.
  5. Sainio S, Järvenpää AL, Renlund M, et al. Thrombocytopenia in term infants: a population-based study. Obstet Gynecol 2000; 95:441.
  6. Stanworth SJ, Clarke P, Watts T, et al. Prospective, observational study of outcomes in neonates with severe thrombocytopenia. Pediatrics 2009; 124:e826.
  7. Baer VL, Lambert DK, Henry E, Christensen RD. Severe Thrombocytopenia in the NICU. Pediatrics 2009; 124:e1095.
  8. 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.
  9. Castle V, Andrew M, Kelton J, et al. Frequency and mechanism of neonatal thrombocytopenia. J Pediatr 1986; 108:749.
  10. 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.
  11. Kamphuis MM, Paridaans N, Porcelijn L, et al. Screening in pregnancy for fetal or neonatal alloimmune thrombocytopenia: systematic review. BJOG 2010; 117:1335.
  12. Murphy MF, Bussel JB. Advances in the management of alloimmune thrombocytopenia. Br J Haematol 2007; 136:366.
  13. Porcelijn L, Folman CC, de Haas M, et al. Fetal and neonatal thrombopoietin levels in alloimmune thrombocytopenia. Pediatr Res 2002; 52:105.
  14. Bussel JB, Zabusky MR, Berkowitz RL, McFarland JG. Fetal alloimmune thrombocytopenia. N Engl J Med 1997; 337:22.
  15. Bussel JB, Zacharoulis S, Kramer K, et al. Clinical and diagnostic comparison of neonatal alloimmune thrombocytopenia to non-immune cases of thrombocytopenia. Pediatr Blood Cancer 2005; 45:176.
  16. Kaplan C. Immune thrombocytopenia in the foetus and the newborn: diagnosis and therapy. Transfus Clin Biol 2001; 8:311.
  17. Homans A. Thrombocytopenia in the neonate. Pediatr Clin North Am 1996; 43:737.
  18. George D, Bussel JB. Neonatal thrombocytopenia. Semin Thromb Hemost 1995; 21:276.
  19. Davoren A, Curtis BR, Aster RH, McFarland JG. Human platelet antigen-specific alloantibodies implicated in 1162 cases of neonatal alloimmune thrombocytopenia. Transfusion 2004; 44:1220.
  20. Curtis BR, Ali S, Glazier AM, et al. Isoimmunization against CD36 (glycoprotein IV): description of four cases of neonatal isoimmune thrombocytopenia and brief review of the literature. Transfusion 2002; 42:1173.
  21. Rousseau J, Goldman M, David M. HPA-5b (Bra) neonatal alloimmune thrombocytopenia in Quebec: incidence and clinical outcome in 31 cases. Transfusion 2004; 44:844.
  22. Castro V, Kroll H, Origa AF, et al. A prospective study on the prevalence and risk factors for neonatal thrombocytopenia and platelet alloimmunization among 9332 unselected Brazilian newborns. Transfusion 2007; 47:59.
  23. Peterson JA, Gitter ML, Kanack A, et al. New low-frequency platelet glycoprotein polymorphisms associated with neonatal alloimmune thrombocytopenia. Transfusion 2010; 50:324.
  24. Ghevaert C, Campbell K, Walton J, et al. Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia. Transfusion 2007; 47:901.
  25. Knight M, Pierce M, Allen D, et al. The incidence and outcomes of fetomaternal alloimmune thrombocytopenia: a UK national study using three data sources. Br J Haematol 2011; 152:460.
  26. Wilson DB. Acquired platelet defects. In: Nathan and Oski's Hematology of Infancy and Childhood, Nathan DG, Orkin SH, Ginsberg D, Look AT (Eds), WB Saunders, Philadelphia 2003. p.1597.
  27. Killie MK, Husebekk A, Kaplan C, et al. Maternal human platelet antigen-1a antibody level correlates with the platelet count in the newborns: a retrospective study. Transfusion 2007; 47:55.
  28. Gorlin JB, Goorin AM. Hematologic problems: Thrombocytopenia. In: Manual of Neonatal Care, Cloherty JP, Stark AR (Eds), Lippincott-Raven, Philadelphia 1997. p.470.
  29. Kiefel V, Bassler D, Kroll H, et al. Antigen-positive platelet transfusion in neonatal alloimmune thrombocytopenia (NAIT). Blood 2006; 107:3761.
  30. Bennett CM, Rogers ZR, Kinnamon DD, et al. Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura. Blood 2006; 107:2639.
  31. Bassler D, Greinacher A, Okascharoen C, et al. A systematic review and survey of the management of unexpected neonatal alloimmune thrombocytopenia. Transfusion 2008; 48:92.
  32. Kjeldsen-Kragh J, Killie MK, Tomter G, et al. A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia. Blood 2007; 110:833.
  33. Letsky EA, Greaves M. Guidelines on the investigation and management of thrombocytopenia in pregnancy and neonatal alloimmune thrombocytopenia. Maternal and Neonatal Haemostasis Working Party of the Haemostasis and Thrombosis Task Force of the British Society for Haematology. Br J Haematol 1996; 95:21.
  34. Ouwehand WH, Smith G, Ranasinghe E. Management of severe alloimmune thrombocytopenia in the newborn. Arch Dis Child Fetal Neonatal Ed 2000; 82:F173.
  35. Ovali F, Samanci N, Ermiş B, et al. Alternative therapies for neonatal autoimmune thrombocytopenia. Vox Sang 1998; 74:198.
  36. Bussel J. Diagnosis and management of the fetus and neonate with alloimmune thrombocytopenia. J Thromb Haemost 2009; 7 Suppl 1:253.
  37. Kaplan C, Daffos F, Forestier F, et al. Management of alloimmune thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets. Blood 1988; 72:340.
  38. Herman JH, Jumbelic MI, Ancona RJ, Kickler TS. In utero cerebral hemorrhage in alloimmune thrombocytopenia. Am J Pediatr Hematol Oncol 1986; 8:312.
  39. Radder CM, Roelen DL, van de Meer-Prins EM, et al. The immunologic profile of infants born after maternal immunoglobulin treatment and intrauterine platelet transfusions for fetal/neonatal alloimmune thrombocytopenia. Am J Obstet Gynecol 2004; 191:815.
  40. Tchernia G, Morel-Kopp MC, Yvart J, Kaplan C. Neonatal thrombocytopenia and hidden maternal autoimmunity. Br J Haematol 1993; 84:457.
  41. Anteby E, Shalev O. Clinical relevance of gestational thrombocytopenia of < 100,000/microliters. Am J Hematol 1994; 47:118.
  42. Burrows RF, Kelton JG. Pregnancy in patients with idiopathic thrombocytopenic purpura: assessing the risks for the infant at delivery. Obstet Gynecol Surv 1993; 48:781.
  43. Payne SD, Resnik R, Moore TR, et al. Maternal characteristics and risk of severe neonatal thrombocytopenia and intracranial hemorrhage in pregnancies complicated by autoimmune thrombocytopenia. Am J Obstet Gynecol 1997; 177:149.
  44. Valat AS, Caulier MT, Devos P, et al. Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia. Br J Haematol 1998; 103:397.
  45. van den Akker ES, Oepkes D, Lopriore E, et al. Noninvasive antenatal management of fetal and neonatal alloimmune thrombocytopenia: safe and effective. BJOG 2007; 114:469.
  46. Nieminen U, Kekomäki R. Quinidine-induced thrombocytopenic purpura: clinical presentation in relation to drug-dependent and drug-independent platelet antibodies. Br J Haematol 1992; 80:77.
  47. Greaves M, Letsky EA. Guidelines on the investigation and management of thrombocytopenia in pregnancy and neonatal alloimmune thrombocytopenia. Br J Obstet Gynaecol 1997; 104:1108.
  48. Kelton JG, Meltzer D, Moore J, et al. Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro. Blood 1981; 58:524.
  49. Couser RJ, Ferrara TB, Wright GB, et al. Prophylactic indomethacin therapy in the first twenty-four hours of life for the prevention of patent ductus arteriosus in preterm infants treated prophylactically with surfactant in the delivery room. J Pediatr 1996; 128:631.
  50. Kumar RK, Yu VY. Prolonged low-dose indomethacin therapy for patent ductus arteriosus in very low birthweight infants. J Paediatr Child Health 1997; 33:38.
  51. Kasabach HH, Merritt KK. Hemangioma with extensive purpura. Arch Dis Child 1940; 59:1063.
  52. Blei F. New clinical observations in hemangiomas. Semin Cutan Med Surg 1999; 18:187.
  53. Enjolras O, Wassef M, Mazoyer E, et al. Infants with Kasabach-Merritt syndrome do not have "true" hemangiomas. J Pediatr 1997; 130:631.
  54. Propp RP, Scharfman WB. Hemangioma-thrombocytopenia syndrome associated with microangiopathic hemolytic anemia. Blood 1966; 28:623.
  55. Hall GW. Kasabach-Merritt syndrome: pathogenesis and management. Br J Haematol 2001; 112:851.
  56. Blei F, Karp N, Rofsky N, et al. Successful multimodal therapy for kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon: case report and review of the literature. Pediatr Hematol Oncol 1998; 15:295.
  57. Andrew M, Brooker LA. Hemostatic disorders in newborns. In: Avery's Diseases of the Newborn, Taeusch HW, Ballard RA (Eds), WB Saunders, Philadelphia 1998. p.1045.
  58. Cooper LZ, Green RH, Krugman S, et al. Neonatal thrombocytopenic purpura and other manifestations of rubella contracted in utero. Am J Dis Child 1965; 110:416.
  59. Oski FA, Naiman JL. Effect of live measles vaccine on the platelet count. N Engl J Med 1966; 275:352.
  60. Whitley RJ, Cloud G, Gruber W, et al. Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis 1997; 175:1080.
  61. Ververidis M, Kiely EM, Spitz L, et al. The clinical significance of thrombocytopenia in neonates with necrotizing enterocolitis. J Pediatr Surg 2001; 36:799.
  62. Jones KL. Smith's recognizable patterns of human malformation, 6th ed, Elsevier Saunders, Philadelphia 2006.
  63. Letestu R, Vitrat N, Massé A, et al. Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome. Blood 2000; 95:1633.
  64. Hedberg VA, Lipton JM. Thrombocytopenia with absent radii. A review of 100 cases. Am J Pediatr Hematol Oncol 1988; 10:51.
  65. Ballmaier M, Germeshausen M, Schulze H, et al. c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia. Blood 2001; 97:139.
  66. van den Oudenrijn S, Bruin M, Folman CC, et al. Three parameters, plasma thrombopoietin levels, plasma glycocalicin levels and megakaryocyte culture, distinguish between different causes of congenital thrombocytopenia. Br J Haematol 2002; 117:390.
  67. Hord JD, Gay JC, Whitlock JA. Thrombocytopenia in neonates with trisomy 21. Arch Pediatr Adolesc Med 1995; 149:824.
  68. Hohlfeld P, Forestier F, Kaplan C, et al. Fetal thrombocytopenia: a retrospective survey of 5,194 fetal blood samplings. Blood 1994; 84:1851.
  69. Cohen IJ. Cold injury in early infancy. Isr J Med Sci 1977; 13:405.
  70. Cohen IJ, Amir J, Gedaliah A, et al. Thrombocytopenia of neonatal cold injury. J Pediatr 1984; 104:620.
  71. Cohen IJ. Room temperature ADP-induced first-stage hyperaggregation of human platelets: the cause of rewarming deaths by thrombocytopenia in neonatal cold injury. Pediatr Hematol Oncol 1991; 8:61.
  72. Ropert JC, Dreyfus M, Dehan M, Tchernia G. [Severe neonatal thrombopenia. Analysis of the etiologic data on 64 cases]. Arch Fr Pediatr 1984; 41:85.
  73. Oren H, Irken G, Oren B, et al. Assessment of clinical impact and predisposing factors for neonatal thrombocytopenia. Indian J Pediatr 1994; 61:551.
  74. Grainick HR, Williams SB, McKeown LP, et al. Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor. J Clin Invest 1985; 76:1522.
  75. Ruggeri ZM, Pareti FI, Mannucci PM, et al. Heightened interaction between platelets and factor VIII/von Willebrand factor in a new subtype of von Willebrand's disease. N Engl J Med 1980; 302:1047.
  76. Fressinaud E, Mazurier C, Meyer D. Molecular genetics of type 2 von Willebrand disease. Int J Hematol 2002; 75:9.
  77. Murray NA, Roberts IA. Circulating megakaryocytes and their progenitors in early thrombocytopenia in preterm neonates. Pediatr Res 1996; 40:112.
  78. Koenig JM, Christensen RD. Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med 1989; 321:557.
  79. 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.
  80. Andrew M, Vegh P, Caco C, et al. A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants. J Pediatr 1993; 123:285.
  81. 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.
  82. Bonifacio L, Petrova A, Nanjundaswamy S, Mehta R. Thrombocytopenia related neonatal outcome in preterms. Indian J Pediatr 2007; 74:269.
  83. 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.
  84. Calhoun DA, Christensen RD, Edstrom CS, et al. Consistent approaches to procedures and practices in neonatal hematology. Clin Perinatol 2000; 27:733.
  85. Honohan A, van't Ende E, Hulzebos C, et al. Posttransfusion platelet increments after different platelet products in neonates: a retrospective cohort study. Transfusion 2013; 53:3100.