Semin Thromb Hemost 2007; 33(8): 816-820
DOI: 10.1055/s-2007-1000373
© Thieme Medical Publishers

Coagulation Testing in Pediatric Patients: The Young Are Not Just Miniature Adults

Giuseppe Lippi1 , Massimo Franchini2 , Martina Montagnana3 , Gian Cesare Guidi1
  • 1Professor, Sezione di Chimica Clinica, Dipartimento di Scienze Biomediche e Morfologiche, Università di Verona, Verona, Italy
  • 2Servizio di Immunoematologia e Trasfusione - Centro Emofilia, Azienda Ospedaliera di Verona, Verona, Italy
  • 3Sezione di Chimica Clinica, Dipartimento di Scienze Biomediche e Morfologiche, Università di Verona, Verona, Italy
Further Information

Publication History

Publication Date:
04 January 2008 (online)

ABSTRACT

During the past few decades, great progress has been made toward a better understanding of the development of the hemostatic system. It is now clear that the physiology of hemostasis in pediatric patients differs widely from that in adults, supporting the hypothesis that children might have natural protective mechanisms that justify such variations. However, the correct interpretation of hemostasis test results in young patients, along with a deep understanding of the normal postnatal development in the human coagulation system, are essential prerequisites to the proper investigation of thrombotic and hemorrhagic problems in pediatric patients. Because the hemostatic system is not fully mature by 3 to 6 months of age, it is important to recognize that interpretation of laboratory data in pediatric patients must be accompanied by appropriate age-dependent reference ranges, which should also be specific for the testing system used, to prevent misclassification of children as having defects of factors and inhibitors of the coagulation system.

REFERENCES

  • 1 Bleyer W A, Hakami N, Shepard T H. The development of hemostasis in the human fetus and newborn infant.  J Pediatr. 1971;  79 838-853
  • 2 Kenet G, Nowak-Gottl U. Bleeding and thrombosis issues in pediatric patients: current approach to diagnosis and treatment.  Acta Haematol. 2006;  115 137-140
  • 3 Hassan H J, Leonardi A, Chelucci C et al.. Blood coagulation factors in human embryonic development: preferential expression of the FVII/tissue factor pathway.  Blood. 1990;  76 1158-1164
  • 4 Karpatkin M, Blei F, Hurlet A, Greco A, Tang Z. Prothrombin expression in the adult and fetal rabbit liver.  Pediatr Res. 1991;  30 266-269
  • 5 Saleh A A, Alshameeri R S, O'Brien J M et al.. Maternal and neonatal primary hemostasis.  Thromb Res. 1994;  73 125-129
  • 6 Manco-Johnson M, Nuss R. Hemostasis in the neonate.  Neo Rev. 2000;  1 e191-e195
  • 7 Franchini M, Lippi G, Veneri D, Targher G, Zaffanello M, Guidi G C. Inherited platelet disorders.  Clin Chim Acta. 2008;  387 1-8
  • 8 Franchini M, Lippi G. The role of von Willebrand factor in hemorrhagic and thrombotic disorders.  Crit Rev Clin Lab Sci. 2007;  44 115-149
  • 9 Sutor A H. New aspects of vitamin K prophylaxis.  Semin Thromb Hemost. 2003;  29 373-376
  • 10 Hathaway W E. Insights on vitamin K.  Hematol Oncol Clin North Am. 1987;  1 367-379
  • 11 Cornelissen E A, Kollee L A, De Abreu R A et al.. Effects of oral and intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II, and clotting factors in breast fed infants.  Arch Dis Child. 1992;  67 1250-1254
  • 12 Karpatkin M. Coagulation problems in the newborn.  Semin Neonatol. 1999;  4 67-73
  • 13 Nowak-Gottl U, Kosch A, Schlegel N. Neonatal thromboembolism.  Semin Thromb Hemost. 2003;  29 227-234
  • 14 Heller C, Nowak-Gottl U. Maternal thrombophilia and neonatal thrombosis.  Best Pract Res Clin Haematol. 2003;  16 333-345
  • 15 Nowak-Göttl U, Kosch A, Schlegel N, Salem M, Manco-Johnson M. Thromboembolism in children.  Curr Opin Hematol. 2002;  9 448-453
  • 16 Nowak-Gottl U, Duering C, Kempf-Bielack B, Strater R. Thromboembolic diseases in neonates and children.  Pathophysiol Haemost Thromb. 2003;  33 269-274
  • 17 Greenway A, Massicotte M P, Monagle P. Neonatal thrombosis and its treatment.  Blood Rev. 2004;  18 75-84
  • 18 Marlar R A, Neumann A. Neonatal purpura fulminans due to homozygous protein C or protein S deficiencies.  Semin Thromb Hemost. 1990;  16 299-309
  • 19 Beardsley D S. Venous thromboemebolism in the neonatal period.  Semin Perinatol. 2007;  31 250-253
  • 20 Andrew M. Developmental hemostasis relevance to thromboembolic complications in pediatric patients.  Thromb Haemost. 1995;  74 415-425
  • 21 Monagle P, Barnes C, Ignjatovic V et al.. Developmental haemostasis. Impact for clinical haemostasis laboratories.  Thromb Haemost. 2006;  95 362-372
  • 22 Pysher T J, Bach P R, Geaghan S M et al.. Teaching pediatric laboratory medicine to pathology residents.  Arch Pathol Lab Med. 2006;  130 1031-1038
  • 23 Andrew M, Paes B, Johnston M. Development of the haemostatic system in the neonate and young infant.  Am J Pediatr Hematol Oncol. 1990;  12 95-104
  • 24 Andrew M, Paes B, Milner R et al.. Development of the human coagulation system in the full-term infant.  Blood. 1987;  70 165-172
  • 25 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood.  Blood. 1992;  80 1998-2005
  • 26 Andrew M, Bhogal M, Karpatkin M. Factors XI and XII and prekallikrein in sick and healthy premature infants.  N Engl J Med. 1981;  305 1130-1133
  • 27 Andrew M, Paes B, Milner R et al.. Development of the human coagulation system in the healthy premature infant.  Blood. 1988;  72 1651-1657
  • 28 Karpatkin M, Mannucci P M, Bhogal M, Vigano S, Nardi M. Low protein C in the neonatal period.  Br J Haematol. 1986;  62 137-142
  • 29 Cohen L, McKinnell J, Puglisi V et al.. Prothrombin synthesis in the adult and fetal liver.  Thromb Haemost. 1997;  78 1468-1472
  • 30 Lippi G, Salvagno G L, Rugolotto S et al.. Routine coagulation tests in newborn and young infants.  J Thromb Thrombolysis. 2007;  24 153-155
  • 31 Flanders M M, Crist R A, Roberts W L, Rodgers G M. Pediatric reference intervals for seven common coagulation assays.  Clin Chem. 2005;  51 1738-1742
  • 32 Flanders M M, Phansalkar A R, Crist R A, Roberts W L, Rodgers G M. Pediatric reference intervals for uncommon bleeding and thrombotic disorders.  J Pediatr. 2006;  149 275-277
  • 33 Andrew M, Mitchell L, Vegh P. Thrombin regulation in children differs from adults in the absence and presence of heparin.  Thromb Haemost. 1994;  72 836-842
  • 34 Fritsch P, Cvirn G, Cimenti C et al.. Thrombin generation in factor VIII-depleted neonatal plasma: nearly normal because of physiologically low antithrombin and tissue factor pathway inhibitor.  J Thromb Haemost. 2006;  4 1071-1077
  • 35 Albisetti M. The fibrinolytic system in children.  Semin Thromb Hemost. 2003;  29 339-348
  • 36 Parmar N, Albisetti M, Berry L R, Chan A K. The fibrinolytic system in newborns and children.  Clin Lab. 2006;  52 115-124
  • 37 Parmar N, Mitchell L G, Berry L R, Andrew M, Chan A K. The influence of age on in vitro plasmin generation in the presence of fibrin monomer.  Acta Haematol. 2006;  115 141-151
  • 38 Sosothikul D, Seksarn P, Lusher J M. Pediatric reference values for molecular markers in hemostasis.  J Pediatr Hematol Oncol. 2007;  29 19-22
  • 39 Rand M L, Kuhle S. Platelets and platelet function testing in children.  Prog Pediatr Cardiol. 2005;  21 63-69
  • 40 Thornburg C, Pipe S. Neonatal thromboembolic emergencies.  Semin Fetal Neonatal Med. 2006;  11 198-206

Prof. Giuseppe Lippi 

Sezione di Chimica Clinica, Dipartimento di Scienze Morfologico-Biomediche, Ospedale Policlinico G.B. Rossi

Piazzale Scuro, 10, 37134 Verona, Italy

Email: giuseppe.lippi@univr.it

Email: ulippi@tin.it

    >