Neonatology pp 748-762 | Cite as

Pathophysiology of Coagulation and Deficiencies of Coagulation Factors in the Newborn

  • Rodney P. A. Rivers


The main points of difference between neonatal and adult hemostasis are as follows:
  • Platelets show significant differences in function

  • Bleeding times are shorter through increased activity of von Willebrand factor (VWF)

  • Increased tissue factor (TF) availability from monocytes and microparticles

  • Many procoagulant and inhibitor levels are gestationally dependent

  • Thrombin generation equivalent to adult

  • Reduced procoagulant and inhibitor reserve

  • Relatively impaired fibrinolysis

  • In both, normal screening test results do not equate with normal hemostasis.


Disseminate Intravascular Coagulation Fresh Freeze Plasma Thrombin Generation Activate Partial Thromboplastin Time Prothrombin Complex Concentrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Hathaway W, Corrigan J (1991) Report of Scientific and Standardization Subcommittee on Neonatal Hemostasis. Normal coagulation data for fetuses and newborn infants. Thromb Haemost 65: 323–325Google Scholar
  2. 2.
    Holmberg L, Henriksson P, Ekelund H et al (1974) Coagulation in the human fetus. Comparison with term newborn infants. J Pediatr 85: 860–864Google Scholar
  3. 3.
    Barnard DR, Simmons MA, Hathaway WE (1979) Coagulation studies in extremely premature infants. Pediatr Res 13: 1330–1335PubMedCrossRefGoogle Scholar
  4. 4.
    Jensen H, Josso F, Zamet P et al (1973) Evolution of blood clotting factor levels in premature infants during the first 10 days of life: a study of 96 cases with comparison between clinical status and blood clotting factor levels. Pediatr Res 7: 638–644PubMedCrossRefGoogle Scholar
  5. 5.
    Salonvaara M, Riikonen P, Vahtera E et al (2004) Development of selected coagulation factors and anticoagulants in preterm infants by the age of six months. Thromb Haemost 92: 688–696PubMedGoogle Scholar
  6. 6.
    Cvirn G, Gallistl S, Koestenberger M et al (2002) Alpha 2-macroglobulin enhances prothrombin activation and thrombin potential by inhibiting the anticoagulant protein C/protein S system in cord and adult plasma. Thromb Res 105: 433–439PubMedCrossRefGoogle Scholar
  7. 7.
    Långström S, Wartiovaara-Kautto U, Andersson S et al (2006) Exchange transfusion activates coagulation and alters the coagulation profile in newborn infants. Thromb Haemost 96: 142–148PubMedGoogle Scholar
  8. 8.
    Andrew M, Vegh P, Johnston M et al (1992) Maturation of the hemostatic system during childhood. Blood 80: 1998–2005PubMedGoogle Scholar
  9. 9.
    Andrew M, Paes B, Milner R et al (1987) Development of the human coagulation system in the full-term infant. Blood 70: 165–172PubMedGoogle Scholar
  10. 10.
    Andrew M, Paes B, Milner R et al (1988) Development of the human coagulation system in the healthy premature infant. Blood 72: 1651–1657PubMedGoogle Scholar
  11. 11.
    Monagle P, Barnes C, Ignjatovic V et al (2006) Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost 95: 362–372Google Scholar
  12. 12.
    Wiedmeier SE, Henry E, Sola-Visner MC et al (2009) Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J Perinatol 29: 130–136PubMedCrossRefGoogle Scholar
  13. 13.
    Israels SJ, Rand ML, Michelson AD (2003) Neonatal platelet function. Semin Thromb Hemost 29: 363–372PubMedCrossRefGoogle Scholar
  14. 14.
    Saxonhouse MA, Manco-Johnson M (2009) The evaluation and management of neonatal coagulation disorders. Semin Perinatol 33: 52 - 65PubMedCrossRefGoogle Scholar
  15. 15.
    Cvirn G, Kutschera J, Wagner T et al (2009) Collagen/endogenous thrombin-induced platelet aggregation in cord versus adult whole blood. Neonatology 95: 187–192PubMedCrossRefGoogle Scholar
  16. 16.
    Bernhard H, Rosenkranz A, Petritsch M et al (2009) Phospholipid content, expression and support of thrombin generation of neonatal platelets. Acta Paediatr 98: 251–255PubMedCrossRefGoogle Scholar
  17. 17.
    Cvirn G, Gallistl S, Muntean W (1999) Effects of antithrombin and protein C on thrombin generation in newborn and adult plasma. Thromb Res 93: 183–190PubMedCrossRefGoogle Scholar
  18. 18.
    Cvirn G, Gruber HJ, Koestenberger M et al (2007) High availability of intravascular tissue factor in neonates. J Pediatr Hematol Oncol 29: 279–283PubMedCrossRefGoogle Scholar
  19. 19.
    Karimi M, Bereczky Z, Cohan N et al (2009) Factor XIII Deficiency. Semin Thromb Hemost 35: 426–438PubMedCrossRefGoogle Scholar
  20. 20.
    Chalmers EA (2004) Haemophilia and the newborn. Blood Rev 18: 85–92PubMedCrossRefGoogle Scholar
  21. 21.
    Goodeve A (2008) Molecular genetic testing of hemophilia A. Semin Thromb Hemost. 34: 491–501PubMedCrossRefGoogle Scholar
  22. 22.
    Ljung RC (2008) Intracranial haemorrhage in haemophilia A and B. Br J Haematol 140: 378–384PubMedCrossRefGoogle Scholar
  23. 23.
    Street AM, Ljung R, Lavery SA (2008) Management of carriers and babies with haemophilia. Haemophilia 14 (Suppl 3): 181–187PubMedCrossRefGoogle Scholar
  24. 24.
    Fritsch P, Cvirn G, Cimenti C et al (2006) Thrombin generation in factor VIII-depleted neonatal plasma: nearly normal because of physiologically low antithrombin and tissue factor pathway inhibitor. J Thromb Haemost 4: 1071–1077PubMedCrossRefGoogle Scholar
  25. 25.
    Kulkarni R, Lusher J (2001) Perinatal management of newborns with haemophilia. Br J Haematol 112: 264–274PubMedCrossRefGoogle Scholar
  26. 26.
    Astermark J, Lacroix-Desmazes S, Reding MT (2008) Inhibitor development. Haemophilia 14 (Suppl 3): 36–42PubMedCrossRefGoogle Scholar
  27. 27.
    Nichols WL, Hultin MB, James AH et al (2008) von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report ( USA ). Haemophilia 14: 171–232Google Scholar
  28. 28.
    Peyvandi F, Cattaneo M, Inbal A et al (2008) Rare bleeding disorders. Haemophilia 14 (Suppl 3): 202–210PubMedCrossRefGoogle Scholar
  29. 29.
    Peyvandi F, Palla R, Menegatti M et al (2009) Introduction. Rare bleeding disorders: general aspects of clinical features, diagnosis, and management. Semin Thromb Hemost. 35: 349–355PubMedCrossRefGoogle Scholar
  30. 30.
    Bolton-Maggs PH, Perry DJ, Chalmers EA et al (2004) The rare coagulation disorders—review with guidelines for management from the United Kingdom Haemophilia Centre Doctors’ Organisation. Haemophilia 10: 593–628PubMedCrossRefGoogle Scholar
  31. 31.
    de Moerloose P, Neerman-Arbez M (2009) Congenital fibrinogen disorders. Semin Thromb Hemost. 35: 356–366PubMedCrossRefGoogle Scholar
  32. 32.
    Girolami A, Scandellari R, Scapin M et al (2008) Congenital bleeding disorders of the vitamin K-dependent clotting factors. Vitam Horm 78: 281–374PubMedCrossRefGoogle Scholar
  33. 33.
    Lancellotti S, De Cristofaro R (2009) Congenital prothrombin deficiency. Semin Thromb Hemost 35: 367–381PubMedCrossRefGoogle Scholar
  34. 34.
    Asselta R, Peyvandi F (2009) Factor V deficiency. Semin Thromb Hemost 35: 382–389PubMedCrossRefGoogle Scholar
  35. 35.
    Mariani G BF (2009) Factor VII Deficiency. SeminThromb Hemost 35: 400–406PubMedCrossRefGoogle Scholar
  36. 36.
    Menegatti M, Peyvandi F (2009) Factor X deficiency. Semin Thromb Hemost 35: 407–415PubMedCrossRefGoogle Scholar
  37. 37.
    Duga S, Salomon O (2009) Factor XI Deficiency. Semin Thromb Hemost 35: 416 - 425PubMedCrossRefGoogle Scholar
  38. 38.
    Sutor AH, von Kries R, Cornelissen EA et al (1999) Vitamin K deficiency bleeding (VKDB) in infancy. ISTH Pediatric/Perinatal Subcommittee. International Society on Thrombosis and Haemostasis. Thromb Haemost 81: 456–461Google Scholar
  39. 39.
    McCarthy PT, Shearer MJ, Crampton OC et al (1986) Vitamin K content of human liver at different ages. Rec Adv New Dev Hemostaseology. Haemostasis 16 (suppl 5): 84Google Scholar
  40. 40.
    von Kries R, Becker A, Göbel U (1987) Vitamin K in the newborn: influence of nutritional factors on acarboxy-prothrombin detectability and factor II and VII clotting activity. Eur J Pediatr 146: 123–127CrossRefGoogle Scholar
  41. 41.
    Puckett RM, Offringa M (2000) Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. Cochrane Database Syst Rev 4: CD002776Google Scholar
  42. 42.
    Shearer MJ (2009) Vitamin K deficiency bleeding (VKDB) in early infancy. Blood Rev 23: 49–59PubMedCrossRefGoogle Scholar
  43. 43.
    Golding J, Paterson M, Kinlen LJ (1990) Factors associated with childhood cancer in a national cohort study. Br J Cancer 62: 304–308PubMedCrossRefGoogle Scholar
  44. 44.
    Golding J, Greenwood R, Birmingham K et al (1992) Childhood cancer, intramuscular vitamin K, and pethidine given during labour. BMJ 305: 341–346PubMedCrossRefGoogle Scholar
  45. 45.
    Parker L, Cole M, Craft AW et al (1998) Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case-control study. BMJ 316: 189–193PubMedCrossRefGoogle Scholar
  46. 46.
    Passmore SJ, Draper G, Brownbill P et al (1998) Case-control studies of relation between childhood cancer and neonatal vitamin K administration. BMJ 316: 178–184PubMedCrossRefGoogle Scholar
  47. 47.
    Clarke P, Mitchell SJ, Wynn R et al (2006) Vitamin K prophylaxis for preterm infants: a randomized, controlled trial of 3 regimens. Pediatrics 118: e1657–e1666PubMedCrossRefGoogle Scholar
  48. 48.
    Pichler E, Pichler L (2008) The neonatal coagulation system and the vitamin K deficiency bleeding–a mini review. Wien Med Wochenschr 158: 385–395PubMedCrossRefGoogle Scholar
  49. 49.
    Van Winckel M, De Bruyne R, Van De Velde S (2009) Vitamin K, an update for the paediatrician. Eur J Pediatr 168: 127–134PubMedCrossRefGoogle Scholar
  50. 50.
    Widdershoven J, Motohara K, Endo F et al (1986) Influence of the type of feeding on the presence of PIVKA-II in infants. Helv Paediatr Acta 41: 25–29PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Rodney P. A. Rivers
    • 1
  1. 1.Section of Paediatrics, Department of MedicineImperial CollegeLondonUK

Personalised recommendations