Neonatal haemostasis

Summary

The maturation and postnatal development of the human coagulation system results in significant and important differences in the coagulation and fibrinolysis of neonates and young children compared to older children and adults. Importantly, these differences, which mostly reflect the immaturity of the neonatal haemostasis system, are functionally balanced. Healthy neonates show no signs of easy bruising or other bleeding diathesis and no increased tendency to thrombosis for any given stimulus compared to adults.

Systemic diseases may affect haemostasis, thus predisposing ill neonates to increased risk for haemorrhagic or thrombotic complications. In hospitalized children, neonates have increased risk of developing thrombosis compared to infants and children, mostly associated with the presence of central venous catheter. For diagnosis of haemostasis disorders, diagnostic laboratories processing pediatric samples should use age, analyzer and reagent appropriate reference ranges. Age specific guidelines should be followed for the management of neonates with hemostatic disorders.

Zusammenfassung

Durch die Reifung und postnatale Entwick-lung des menschlichen Gerinnungssystems weisen Blutgerinnung und Fibrinolyse bei Neugeborenen und Kleinkindern wesentliche Unterschiede gegenüber älteren Kindern und Erwachsenen auf. Entscheidend ist, dass diese Unterschiede, meist Ausdruck der Unreife des neonatalen Hämostasesystems, funktional ausgeglichen sind. Gesunde Neugeborene zeigen im Vergleich zu Erwachsenen weder Neigung zu Hämatombildung oder anderen hämorrhagischen Diathesen noch eine verstärkte Thrombosetendenz jedweder Ursache.

Systemische Krankheiten können sich auf die Hämostase auswirken und so das Risiko für hämorrhagische oder thrombotische Komplikationen bei kranken Neugeborenen erhöhen. Neugeborene haben unter hospitalisierten Kindern ein höheres Risiko, Thrombosen zu entwickeln als Säuglinge und Kinder, meist in Zusammenhang mit einem zentralen Venenkatheter. Bei der Diagnose von Gerinnungsstörungen sollten diagnostische Labore, die pädiatrische Proben verarbeiten, Referenzwerte anwenden, die für das Alter, Analysegerät und Reagenz geeignet sind. Es sollten die altersspezifischen Richtlinien für die Behandlung von Neugeborenen mit Gerinnungsstörungen befolgt werden.

Keywords

Neonate - bleeding - thrombosis - laboratory evaluation

Schlüsselwörter

Neugeborene - Blutung - Thrombose - Laboruntersuchung

• References

• 1 Revel-Vilk S. The conundrum of neonatal coagulopathy. Hematology Am Soc Hematol Educ Program 2012; 2012: 450-454.
• 2 Monagle P, Massicotte P. Developmental hemostasis: secondary hemostasis. Semin Fetal Neo natal Med 2011; 16: 294-300.
• 3 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: 130-136.
• 4 Strauss T, Sidlik-Muskatel R, Kenet G. Developmental hemostasis: primary haemostasis and evaluation of platelet function in neonates. Semin Fetal Neo natal Med 2011; 16: 301-304.
• 5 Israels SJ. Diagnostic evaluation of platelet function disorders in neonates and children: an update. Semin Thromb Hemost 2009; 35: 181-188.
• 6 Del Vecchio A, Latini G, Henry E, Christensen RD. Template bleeding times of 240 neonates born at 24 to 41 weeks gestation. J Perinatol 2008; 28: 427-431.
• 7 Carcao MD, Blanchette VS, Dean JA. et al. The Platelet Function Analyzer (PFA-100): a novel invitro system for evaluation of primary hemostasis in children. Br J Haematol 1998; 101: 70-73.
• 8 Strauss T, Levy-Shraga Y, Ravid B. et al. Clot formation of neonates tested by thromboelastography correlates with gestational age. Thromb Haemost 2010; 103: 344-350.
• 9 Oswald E, Stalzer B, Heitz E. et al. Thromboelastometry (ROTEM®) in children: Age-related reference ranges and correlations with standard coagulation tests. Br J Anaesth 2010; 105: 827-835.
• 10 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70: 165-172.
• 11 Katz JA, Moake JL, McPherson PD. et al. Relationship between human development and disappearance of unusually large von Willebrand factor multimers from plasma. Blood 1989; 73: 1851-1858.
• 12 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72: 1651-1657.
• 13 Monagle P, Barnes C, Ignjatovic V. et al. Developmental hemostasis. Impact for clinical hemostasis laboratories. Thromb Haemost 2006; 95: 362-372.
• 14 Ignjatovic V, Mertyn E, Monagle P. The coagulation system in children: developmental and pathophysiological considerations. Semin Thromb Hemost 2011; 37: 723-729.
• 15 Ignjatovic V, Lai C, Summerhayes R. et al. Age-related differences in plasma proteins: how plasma proteins change from neonates to adults. PloS One 2011; 6: e17213.
• 16 Guzzetta NA, Miller BE. Principles of hemostasis in children: models and maturation. Paediatr Anaesth 2011; 21: 3-9.
• 17 Miller BE, Tosone SR, Guzzetta NA. et al. Fibrinogen in children undergoing cardiac surgery: is it effective?. Anesth Analg 2004; 99: 1341-1346.
• 18 Parmar N, Albisetti M, Berry LR, Chan AK. The fibrinolytic system in newborns and children. Clin Lab 2006; 52: 115-124.
• 19 Nowak-Göttl U, Limperger V, Bauer A. et al. Bleeding issues in neonates and infants – update 2015. Thromb Res 2015; 135 (Suppl. 01) S41-S43.
• 20 Ivanov D, Shabalov N, Petrenko Y. et al. The specific characteristics of DIC syndrome vary with different clinical settings in the newborn. J Matern Fetal Neonatal Med 2014; 27: 1088-1092.
• 21 Sola-Visner M, Sallmon H, Brown R. New insights into the mechanisms of nonimmune thrombocytopenia in neonates. Semin Perinatol 2009; 33: 43-51.
• 22 Sheffield MJ, Lambert DK, Henry E, Christensen RD. Effect of ampicillin on the bleeding time of neonatal intensive care unit patients. J Perinatol 2010; 30: 527-530.
• 23 Sola MC, del Vecchio A, Edwards TJ. et al. The relationship between hematocrit and bleeding time in very low birth weight infants during the first week of life. J Perinatol 2001; 21: 368-371.
• 24 Haizinger B, Gombotz H, Rehak P. et al. Activated thrombelastogram in neonates and infants with complex congenital heart disease in comparison with healthy children. Br J Anaesth 2006; 97: 545-552.
• 25 Curtis BR. Recent progress in understanding the pathogenesis of fetal and neonatal alloimmune thrombocytopenia. Br J Haematol 2015; 171: 671-682.
• 26 Peterson JA, McFarland JG, Curtis BR, Aster RH. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management. Br J Haematol 2013; 161: 3-14.
• 27 Avila L, Barnard D. Bleeding in the neonate. In: Blanchette VK, Breakey VR, Revel-Vilk S. (eds). Sickkids Handbook of Pediatric Thrombosis and hemostasis. Basel: Karger; 2013: 23-41.
• 28 Owens R. Intraventricular hemorrhage in the premature neonate. Neonatal Netw 2005; 24: 55-71.
• 29 Sentilhes L, Leroux P, Radi S. et al. Influence of gestational age on fibrinolysis from birth to postnatal day 10. J Pediatr 2011; 158: 377-382.
• 30 Kuperman AA, Kenet G, Papadakis E, Brenner B. Intraventricular hemorrhage in preterm infants: coagulation perspectives. Semin Thromb Hemost 2011; 37: 730-736.
• 31 Sandoval JA, Sheehan MP, Stonerock CE. et al. Incidence, risk factors, and treatment patterns for deep venous thrombosis in hospitalized children: an increasing population at risk. J Vascul Surg 2008; 47: 837-843.
• 32 Revel-Vilk S, Ergaz Z. Diagnosis and management of central-line-associated thrombosis in newborns and infants. Semin Fetal Neonatal Med 2011; 16: 340-344.
• 33 Saracco P, Parodi E, Fabris C. et al. Management and investigation of neonatal thromboembolic events: genetic and acquired risk factors. Thromb Res 2009; 123: 805-809.
• 34 Trenor 3^rd CC. Thrombosis and thrombophilia: principles for pediatric patients. Blood Coagul Fibrinolysis 2010; 21 (Suppl. 01) S11-S15.
• 35 El Beshlawy A, Alaraby I, Abou Hussein H. et al. Study of protein C, protein S, and antithrombin III in newborns with sepsis. Pediat Crit Care Med 2010; 11: 52-59.
• 36 Monagle P, Ignjatovic V, Savoia H. hemostasis in neonates and children: pitfalls and dilemmas. Blood Rev 2010; 24: 63-68.
• 37 Yurka HG, Wissler RN, Zanghi CN. et al. The effective concentration of epsilon-aminocaproic Acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesth Analg 2010; 111: 180-184.
• 38 Monagle P, Chan A, Goldenberg NA. et al. Anti-thrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9^th ed). Chest 2012; 141 (Suppl. 02) e737S-e801S.
• 39 Schechter T, Finkelstein Y, Ali M. et al. Unfractionated heparin dosing in young infants: clinical outcomes in a cohort monitored with anti-factor Xa levels. J Thromb Haemost 2012; 10: 368-374.
• 40 Ignjatovic V, Kenet G, Monagle P. Developmental hemostasis: recommendations for laboratories reporting pediatric samples. J Thromb Haemost 2012; 10: 298-300.
• 41 Motta M, Del Vecchio A, Chirico G. Fresh frozen plasma administration in the neonatal intensive care unit: Evidence-based guidelines. Clin Perinatol 2015; 42: 639-650.
• 42 Pal S, Curley A, Stanworth SJ. Interpretation of clotting tests in the neonate. Arch Dis Child Fetal Neonatal Ed 2015; 100: F270-F274.