Neonatology pp 1471-1487 | Cite as

Coagulation Disorders: Clinical Aspects of Platelet Disorders

  • Antonio Del VecchioEmail author
Reference work entry


Platelets contribute to primary hemostasis, and their function is affected by their number and condition. A moderately elevated platelet count in the range of 450,000–600,000/μL is not an uncommon finding in the neonatal population; even thrombocytopenia is common, especially in very sick newborns. An infant with clinical signs of thrombocytopenia but without coagulation abnormalities should prompt examination for hepatosplenomegaly, congenital anomalies, and/or signs of sepsis. Thrombocytopenia can be the result of increased platelet destruction. Common causes include systemic neonatal infection even in the absence of disseminated intravascular coagulation, a localized thrombus in the renal vein or attached to an indwelling catheter or in an ECMO circuit, and placental insufficiency and perinatal hypoxia, especially in preterm babies. In immune thrombocytopenias, autoantibodies, alloantibodies, or drug-dependent antibodies may combine with platelet membranes and produce impairment of platelet function. These mechanisms are responsible for various clinical syndromes, including neonatal alloimmune thrombocytopenia, post-transfusion purpura, and autoimmune thrombocytopenia, which occur in neonates born to mothers with idiopathic thrombocytopenic purpura, systemic lupus erythematosus, lymphoproliferative disorders, or hyperthyroidism. Most cases of decreased platelet production are the consequence of reduced megakaryocytes or impaired platelet production by megakaryocytes, such as congenital amegakaryocytic thrombocytopenia, thrombocytopenia with absent radii syndrome, and chromosomal anomalies. Qualitative disorders of platelets function can be acquired (occurring as a result of medications given to the mother or neonate, NO therapy, or ECMO) or hereditary, which do not cause problems during the neonatal period. Laboratory tests are mandatory for the diagnosis of platelet disorders. Treatment consists of platelet transfusions.


  1. Bader-Meunier B, Tchernia G, Mielot F (1997) Occurrence of myeloproliferative disorders with Noon syndrome. J Pediatr 130:885–889CrossRefGoogle Scholar
  2. Baer VL, Lambert DK, Henry E et al (2007) Do platelet transfusions in the NICU adversely affect survival? Analysis of 1600 thrombocytopenic neonates in a multihospital healthcare system. J Perinatol 27:790–796CrossRefGoogle Scholar
  3. Bednarek FJ, Bean S, Barnard MR, Frelinger AL, Michelson AD (2009) The platelet hyporeactivity of extremely low birth weight neonates is age-dependent. Thromb Res 124:42–45CrossRefGoogle Scholar
  4. Blanchette VS, Rand ML (1997) Platelet disorders in newborn infants: diagnosis and management. Semin Perinatol 21:53–62CrossRefGoogle Scholar
  5. Bussel JB (1997) Immune thrombocytopenia in pregnancy: autoimmune and alloimmune. J Reprod Immunol 37:35–61CrossRefGoogle Scholar
  6. Bussel JB, Corrigan JJ (1995) Platelet and vascular disorders. In: Miller DR, Baehner RL (eds) Blood diseases of infancy and childhood. Mosby, St. Louis, pp 866–923Google Scholar
  7. Bussel JB, Sola-Visner M (2009) Current approaches to the evaluation and management of the fetus and neonate with immune thrombocytopenia. Semin Perinatol 33:35–42CrossRefGoogle Scholar
  8. Chan KL, Summerhayes RG, Ignjatovic V, Horton SB, Monagle PT (2007) Reference values for kaolin-activated thromboelastography in healthy children. Anesth Analg 105:1610–1613CrossRefGoogle Scholar
  9. Cheung PY, Salas E, Schulz R (1997) Nitric oxide and platelet function: implications for neonatology. Semin Perinatol 21:409–417CrossRefGoogle Scholar
  10. Christensen RD (2002) Advances and controversies in neonatal ICU platelet transfusion practice. Adv Pediatr Infect Dis 55:255–269Google Scholar
  11. Christensen RD, Paul DA, Sola-Visner MC, Baer VL (2008) Improving platelet transfusion practices in the neonatal intensive care unit. Transfusion 48:2281–2284CrossRefGoogle Scholar
  12. Christensen RD, Baer VL, Yaish HM (2015) Thrombocytopenia in late preterm and term neonates after perinatal asphyxia. Transfusion 55:187–196CrossRefGoogle Scholar
  13. Clapp DW, Shannon KM, Phibbs RH (2001) Hematologic problems. In: Klaus MH, Fanaroff AA (eds) Care of the high risk neonate. Saunders, Philadelphia, pp 447–479CrossRefGoogle Scholar
  14. Curtis BR (2015) Recent progress in understanding the pathogenesis of fetal and neonatal alloimmune thrombocytopenia. Br J Haematol 171:671–682CrossRefGoogle Scholar
  15. Dame C, Sutor AH (2005) Primary and secondary thrombocytosis in childhood. Br J Haematol 29:165–177CrossRefGoogle Scholar
  16. Del Vecchio A (2002) Use of the bleeding time in the neonatal intensive care unit. Acta Paediatr Suppl 91:82–86CrossRefGoogle Scholar
  17. Del Vecchio A, Sola MC (2000) Performing and interpreting the bleeding time in the neonatal intensive care unit. Clin Perinatol 27:643–654CrossRefGoogle Scholar
  18. Del Vecchio A, Sola MC, Theriaque DW et al (2001) Platelet transfusions in the neonatal intensive care unit: factors predicting which patients will require multiple transfusions. Transfusion 41:803–808CrossRefGoogle Scholar
  19. Del Vecchio A, Sullivan SE, Christensen RD et al (2002) Indomethacin prolongs the bleeding time in neonates significantly more than ibuprofen. Pediatr Res 51:466AGoogle Scholar
  20. Del Vecchio A, Latini G, Henry E, Christensen RD (2008) Template bleeding times of 240 neonates born at 24 to 41 weeks gestation. J Perinatol 28:427–431CrossRefGoogle Scholar
  21. Del Vecchio A, Motta M, Romagnoli C (2015) Neonatal platelet function. Clin Perinatol 42:625–638CrossRefGoogle Scholar
  22. Edstrom CS, Christensen RD, Andrew M (2000) Developmental aspects of blood hemostasis and disorders of coagulation and fibrinolysis in the neonatal period. In: Christensen RD (ed) Hematologic problems of the neonate. Saunders, Philadelphia, pp 239–271Google Scholar
  23. Edwards RM, Naik-Mathuria BJ, Gay AN, Olutoye OO, Teruya J (2008) Parameters of thromboelastography in healthy newborns. Am J Clin Pathol 130:99–102CrossRefGoogle Scholar
  24. El Haouari M, Rosado JA (2009) Platelet function in hypertension. Blood Cells Mol Dis 42:38–43CrossRefGoogle Scholar
  25. Elzey BD, Grant JF, Sinn HW, Nieswandt B, Waldschmidt TJ, Ratliff TL (2005) Cooperation between platelet-derived CD154 and CD4+ T cells for enhanced germinal center formation. J Leukoc Biol 78:80–84CrossRefGoogle Scholar
  26. Gasparini N, Franzese A, Argenziano A (1996) Thrombocytosis in congenital adrenal hyperplasia at diagnosis. Clin Pediatr 35:267–269CrossRefGoogle Scholar
  27. Geddis AE (2009) Congenital amegakaryocytic thrombocytopenia and thrombocytopenia with absent radii. Hematol Oncol Clin North Am 23:321–331CrossRefGoogle Scholar
  28. Gerday E, Baer VL, Lambert DK et al (2009) Testing platelet mass versus platelet count to guide platelet transfusions in the neonatal intensive care unit. Transfusion 49:2034–2039CrossRefGoogle Scholar
  29. Haley KM, Recht M, McCarty OJ (2014) Neonatal platelets: mediators of primary hemostasis in the developing hemostatic system. Pediatr Res 76:230–237CrossRefGoogle Scholar
  30. Halimeh S, Gd A, Sander A, Edelbusch C, Rott H, Thedieck S et al (2010) Multiplate whole blood impedance point of care aggregometry: preliminary reference values in healthy infants, children and adolescents. Klin Padiatr 222:158–163CrossRefGoogle Scholar
  31. Halperin DS, Washer P, Lacourt G (1990) Effects of recombinant human erythropoietin in infants with the anemia of prematurity: a pilot study. J Pediatr 116:779–786CrossRefGoogle Scholar
  32. Handin RI (2003) Blood platelets and the vessel wall. In: Nathan DG (ed) Hematology of infancy and childhood. Saunders, Philadelphia, pp 1457–1474Google Scholar
  33. Hezard N, Amory C, Leroux B, Schlegel N, Potron G, Nguyen P (2002) Platelet hyporeactivity in healthy children remains beyond the neonatal period. Blood 100:69aGoogle Scholar
  34. Israels SJ, Daniels M, McMillan EM (1990) Deficient collagen-induced activation in the newborn platelet. Pediatr Res 27:337–343CrossRefGoogle Scholar
  35. Israels SJ, Odaibo FS, Robertson C, McMillan EM, McNicol A (1997) Deficient thromboxane synthesis and response in platelets from premature infants. Pediatr Res 41:218–223CrossRefGoogle Scholar
  36. Josephson CD, Su LL, Christensen RD et al (2009) Platelet transfusion practices among neonatologists in the United States and Canada: results of a survey. Pediatrics 123:278–285CrossRefGoogle Scholar
  37. Kivivouri SM, Rajantie J, Siimes MA (1996) Peripheral blood cell counts in infants with Down’s syndrome. Clin Genet 49:15–19CrossRefGoogle Scholar
  38. Kühne T, Imbach P (1998) Neonatal platelet physiology and pathophysiology. Eur J Pediatr 157:87–94CrossRefGoogle Scholar
  39. Kuhne T, Ryan G, Blanchette V, Semple JW, Hornstein A, Mody M (1996) Platelet-surface glycoproteins in healthy and preeclamptic mothers and their newborn infants. Pediatr Res 40:876–880CrossRefGoogle Scholar
  40. Li C, Li J, Li Y, Lang S, Yougbare I, Zhu G et al (2012) Crosstalk between platelets and the immune system: old systems with new discoveries. Adv Hematol 2012:384685CrossRefGoogle Scholar
  41. Louden KA, Broughton Pipkin F, Heptinstall S, Fox SC, Tuohy P, O'Callaghan C et al (1994) Neonatal platelet reactivity and serum thromboxane B2 production in whole blood: the effect of maternal low-dose aspirin. Br J Obstet Gynaecol 101:203–208CrossRefGoogle Scholar
  42. MacMillan ML, Davies SM, Wagner JE (1998) Engraftment of unrelated donor stem cells in children with familial amegakaryocytic thrombocytopenia. Bone Marrow Transplant 21:735–737CrossRefGoogle Scholar
  43. Manzoni P (2015) Hematologic aspects of early and late-onset sepsis in preterm infants. Clin Perinatol 42:587–595CrossRefGoogle Scholar
  44. Manzoni P, Arisio R, Mostert M et al (2006) Prophylactic fluconazole is effective in preventing fungal colonization and fungal systemic infections in preterm neonates: a single-center, 6-year, retrospective cohort study. Pediatrics 117:22–32CrossRefGoogle Scholar
  45. Matsubara K, Baba K, Nigami H (2001) Early elevation of serum thrombopoietin levels and subsequent thrombocytosis in healthy preterm infants. Br J Haematol 115:963–968CrossRefGoogle Scholar
  46. McMorran BJ, Marshall VM, de Graaf C, Drysdale KE, Shabbar M, Smyth GK et al (2009) Platelets kill intraerythrocytic malarial parasites and mediate survival to infection. Science 323:797–800CrossRefGoogle Scholar
  47. Murray NA (2002) Evaluation and treatment of thrombocytopenia in the neonatal intensive care unit. Acta Paediatr Suppl 438:74–81CrossRefGoogle Scholar
  48. Murray NA, Howarth LJ, McCloy MP et al (2002) Platelet transfusion in the management of severe thrombocytopenia in neonatal intensive care unit patients. Transfus Med 12:35–41CrossRefGoogle Scholar
  49. Nair S, Ghosh K, Kulkarni B et al (2002) Glanzmann’s thrombasthenia: updated. Platelets 13:387–393CrossRefGoogle Scholar
  50. Nørgaard M, Jensen AØ, Engebjerg MC, Farkas DK, Thomsen RW, Cha S et al (2011) Long-term clinical outcomes of patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Blood 117:3514–3520CrossRefGoogle Scholar
  51. Oncel MY, Erdeve O, Calisici E, Oguz SS, Canpolat FE, Uras N, Dilmen U (2013) The effect of whole-body cooling on hematological and coagulation parameters in asphyxic newborns. Pediatr Hematol Oncol 30:246–252CrossRefGoogle Scholar
  52. Poon MC (2007) The evidence for the use of recombinant human activated factor VII in the treatment of bleeding patients with quantitative and qualitative platelet disorders. Transfus Med Rev 21:223–236CrossRefGoogle Scholar
  53. Radicioni M, Mezzetti D, Del Vecchio A, Motta M (2012) Thromboelastography: might work in neonatology too? J Matern Fetal Neonatal Med 25(Suppl 4):18–21PubMedGoogle Scholar
  54. Rajasekhar D, Barnard MR, Bednarek FJ, Michelson AD (1997) Platelet hyporeactivity in very-low-birth-weight neonates. Thromb Haemost 77:1002–1007CrossRefGoogle Scholar
  55. Roberts I, Stanworth S, Murray NA (2008) Thrombocytopenia in the neonate. Blood Rev 22:173–186CrossRefGoogle Scholar
  56. Sallmon H, Gutti RK, Ferrer-Marin F, Liu ZJ, Sola-Visner MC (2010) Increasing platelets without transfusion: is it time to introduce novel thrombopoietic agents in neonatal care? J Perinatol 30:765–769CrossRefGoogle Scholar
  57. Saxonhouse MA, Sola MC (2004) Platelet function in term and preterm neonates. Clin Perinatol 31:15–28CrossRefGoogle Scholar
  58. Saxonhouse MA, Sola MC, Pastos KM et al (2004) Reticulated platelet percentages in term and preterm neonates. J Pediatr Hematol Oncol 26:797–802PubMedGoogle Scholar
  59. Saxonhouse MA, Rimsza LM, Stevens G et al (2006) Effects of hypoxia on megakaryocyte progenitors obtained from the umbilical cord blood of term and preterm neonates. Biol Neonate 89:104–108CrossRefGoogle Scholar
  60. Semple JW, Freedman J (2010) Platelets and innate immunity. Cell Mol Life Sci 67:499–511CrossRefGoogle Scholar
  61. Sheffield MJ, Schmutz N, Lambert DK et al (2009) Ibuprofen lysine administration to neonates with a patent ductus arteriosus: effect on platelet plug formation assessed by in vivo and in vitro measurements. J Perinatol 29:39–43CrossRefGoogle Scholar
  62. Sola MC, Christensen RD (2000) Developmental aspects of platelets and disorders of platelets in the neonatal period. In: Christensen RD (ed) Hematologic problems of the neonate. Saunders, Philadelphia, pp 273–309Google Scholar
  63. Sola MC, Rimsza LM (2002) Mechanisms underlying thrombocytopenia in the neonatal intensive care unit. Acta Paediatr Suppl 438:66–73CrossRefGoogle Scholar
  64. Sola MC, Rimsza LM, Christensen RD (1999) A bone marrow biopsy technique suitable for use in neonates. Br J Haematol 107:458–460CrossRefGoogle Scholar
  65. Sola MC, Del Vecchio A, Rimsza LM (2000) Evaluation and treatment of thrombocytopenia in the neonatal intensive care unit. Clin Perinatol 27:655–679CrossRefGoogle Scholar
  66. Sola MC, Del Vecchio A, Edwards TJ et al (2001) The relationship between hematocrit and bleeding time in very low birth weight infants during the first week of life. J Perinatol 21:368–371CrossRefGoogle Scholar
  67. Sola-Visner M, Saxonhouse MA, Brown RE (2008) Neonatal thrombocytopenia: what we do and don’t know. Early Hum Dev 84:499–506CrossRefGoogle Scholar
  68. Sola-Visner M, Sallmon H, Brown R (2009) New insights into the mechanisms of nonimmune thrombocytopenia in neonates. Semin Perinatol 33:43–51CrossRefGoogle Scholar
  69. Sparger K, Deschmann E, Sola-Visner M (2015) Platelet transfusion in the neonatal intensive care unit. Clin Perinatol 42:613–623CrossRefGoogle Scholar
  70. Strauss RG (2008) How I transfuse red blood cells and platelets to infants with the anemia and thrombocytopenia of prematurity. Transfusion 48:209–217CrossRefGoogle Scholar
  71. Strauss T, Maayan-Metzger A, Simchen MJ, Morag I, Shenkmean B, Kuint J, Kenet G (2010a) Impaired platelet function in neonates born to mothers with diabetes or hypertension during pregnancy. Klin Padiatr 222:154–157CrossRefGoogle Scholar
  72. Strauss T, Levy-Shraga Y, Ravid B, Schushan-Eisen I, Maayan-Metzger A, Kuint J, Kenet G (2010b) Clot formation of neonates tested by thromboelastography correlates with gestational age. Thromb Haemost 103:344–350CrossRefGoogle Scholar
  73. Sutor AH (1995) Thrombocytosis in childhood. Semin Thromb Hemost 21:330–339CrossRefGoogle Scholar
  74. Velat AS, Caulier MT, Devos P (1998) Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia. Br J Haematol 103:397–401CrossRefGoogle Scholar
  75. Verschoor A, Neuenhahn M, Navarini AA, Graef P, Plaumann A, Seidlmeier A et al (2011) A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3. Nat Immunol 12:1194–1201CrossRefGoogle Scholar
  76. Watts TL, Murray NA, Roberts IAG (1999) Thrombopoietin has a primary role in the regulation of platelet production in preterm babies. Pediatr Res 46:28–32CrossRefGoogle Scholar
  77. Wiedmeier SE, Henry E, Sola-Visner MC, Christensen RD (2009) Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J Perinatol 29:130–136CrossRefGoogle Scholar
  78. Williamson L, Hackett G, Rennie J (1998) The natural history of fetomaternal alloimmunization to the platelet specific antigen HPA-1A as determined by antenatal screening. Blood 92:2280–2287PubMedGoogle Scholar
  79. Zdravic D, Yougbare I, Vadasz B, Li C, Marshall AH, Chen P, Kjeldsen-Kragh J, Ni H (2016) Fetal and neonatal alloimmune thrombocytopenia. Semin Fetal Neonatal Med 21:19–27CrossRefGoogle Scholar
  80. Zipursky A, Jaber HM (1978) The haematology of bacterial infection in newborn infants. Clin Haematol 7:175–193PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Women’s and Children’s Health, Neonatal Intensive Care UnitDi Venere Hospital, ASL BariBariItaly

Personalised recommendations