Developmental Hemostasis: Pro- and Anticoagulant Systems during Childhood

Stefan Kuhle; Christoph Male; Lesley Mitchell

doi:10.1055/s-2003-42584

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2003; 29(4): 329-338
DOI: 10.1055/s-2003-42584

Developmental Hemostasis: Pro- and Anticoagulant Systems during Childhood

Stefan Kuhle¹ , Christoph Male² , Lesley Mitchell³

¹Research Fellow Hospital for Sick Children Population Health Sciences Toronto, Ontario Canada
²Children's Hospital University of Vienna Vienna, Austria
³Hospital for Sick Children, Population Health Sciences, Toronto Ontario, Canada

Abstract

ABSTRACT

An understanding of developmental hemostasis is pivotal for optimal prevention, diagnosis, and treatment of hemostatic problems during childhood. The development of microassays in the early 1980s enabled researchers to delineate age-dependent features of the coagulation system and to establish reference ranges for healthy children of all age groups, from premature infants to adolescents. Based on the results from these studies, the hemostatic system in the young can be described as evolving, and yet functional, since healthy fetuses, infants, and children do not suffer hemorrhagic nor thromboembolic complications spontaneously or in the presence of minor challenges. Plasma concentrations of most pro- and anticoagulant proteins are decreased throughout childhood but provide an effective hemostatic balance on a lower level compared with adults. The current article describes the development of pro- and anticoagulant systems throughout childhood.

KEYWORDS

Coagulation - newborn - children - review

Volltext

Referenzen

REFERENCES

1 Johnston M, Zipursky A. Microtechnology for the study of the blood coagulation system in newborn infants. Can J Med Tech . 1980; 42 159-164
2 Andrew M, Paes B, Milner R. et al . Development of the human coagulation system in the full-term infant. Blood . 1987; 70 165-172
3 Andrew M, Paes B, Milner R. et al . Development of the human coagulation system in the healthy premature infant. Blood . 1988; 72 1651-1657
4 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood . 1992; 80 1998-2005
5 Dahlbäck B. Blood coagulation. Lancet . 2000; 355 1627-1632
6 Cade J F, Hirsh J, Martin M. Placental barrier to coagulation factors: its relevance to the coagulation defect at birth and to haemorrhage in the newborn. Br Med J . 1969; 2 281-283
7 Gitlin D, Biasucci A. Development of gamma G, gamma A, gamma M, beta IC-beta IA, C 1 esterase inhibitor, ceruloplasmin, transferrin, hemopexin, haptoglobin, fibrinogen, plasminogen, alpha₁-antitrypsin, orosomucoid, beta-lipoprotein, alpha2-macroglobulin, and prealbumin in the human conceptus. J Clin Invest . 1969; 48 1433-1446
8 Zilliacus H, Ottelin A M, Mattsson T. Blood clotting and fibrinolysis in human foetuses. Biol Neonat . 1966; 10 108-112
9 Reverdiau-Moalic P, Delahousse B, Body G, Bardos P, Leroy J, Gruel Y. Evolution of blood coagulation activators and inhibitors in the healthy human fetus. Blood . 1996; 88 900-906
10 Mazurier C, Daffos F, Forestier F. Electrophoretic and functional characteristics of the von Willebrand factor in human fetal plasma. Br J Haematol . 1992; 81 263-270
11 Weinstein M J, Blanchard R, Moake J L, Vosburgh E, Moise K. Fetal and neonatal von Willebrand factor (vWF) is unusually large and similar to the vWF in patients with thrombotic thrombocytopenic purpura. Br J Haematol . 1989; 72 68-72
12 Katz J A, Moake J L, McPherson P D. et al . Relationship between human development and disappearance of unusually large von Willebrand factor multimers from plasma. Blood . 1989; 73 1851-1858
13 Thomas K B, Sutor A H, Altinkaya N, Grohmann A, Zehenter A, Leititis J U. von Willebrand factor-collagen binding activity is increased in newborns and infants. Acta Paediatr . 1995; 84 697-699
14 Witt I, Muller H, Künzer W. Evidence for the existence of foetal fibrinogen. Thromb Diath Haemorrhag . 1969; 22 101-109
15 Francis J L, Armstrong D J. Sialic acid and enzymatic desialation of cord blood fibrinogen. Haemostasis . 1982; 11 223-228
16 Hassan H J, Leonardi A, Chelucci C. et al . Blood coagulation factors in human embryonic-fetal development: preferential expression of the FVII/tissue factor pathway. Blood . 1990; 76 1158-1164
17 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
18 Karpatkin M, Lee M, Cohen L, McKinnell J, Nardi M. Synthesis of coagulation proteins in the fetus and neonate. J Pediatr Hematol Oncol . 2000; 22 276-280
19 Holmberg L, Henriksson P, Ekelund H, Åstedt B. Coagulation in the human fetus. Comparison with term newborn infants. J Pediatr . 1974; 85 860-864
20 Kisker C T, Robillard J E, Clarke W R. Development of blood coagulation-a fetal lamb model. Pediatr Res . 1981; 15 1045-1050
21 Andrew M, O'Brodovich H, Mitchell L. Fetal lamb coagulation system during normal birth. Am J Hematol . 1988; 28 116-118
22 McDonald M M, Hathaway W E, Reeve E B, Leonard B D. Biochemical and functional study of antithrombin III in newborn infants. Thromb Haemost . 1982; 47 56-58
23 Schmidt B, Mitchell L, Ofosu F A, Andrew M. Alpha₂-macroglobulin is an important progressive inhibitor of thrombin in neonatal and infant plasma. Thromb Haemost . 1989; 62 1074-1077
24 Cvirn G, Gallistl S, Muntean W. Effects of alpha2-macroglobulin and antithrombin on thrombin generation and inhibition in cord and adult plasma. Thromb Res . 2001; 101 183-191
25 Andrew M, Mitchell L, Berry L. et al . An anticoagulant dermatan sulfate proteoglycan circulates in the pregnant woman and her fetus. J Clin Invest . 1992; 89 321-326
26 Petäjä J, Fernandez J A, Fellman V, Griffin J H. Upregulation of the antithrombotic protein C pathway at birth. Pediatr Hematol Oncol . 1998; 15 489-499
27 Suarez C R, Menendez C E, Walenga J M, Fareed J. Neonatal and maternal hemostasis: value of molecular markers in the assessment of hemostatic status. Semin Thromb Hemost . 1984; 10 280-284
28 Yuen P M, Yin J A, Lao T T. Fibrinopeptide A levels in maternal and newborn plasma. Eur J Obstet Gynecol Reprod Biol . 1989; 30 239-244
29 Greffe B S, Marlar R A, Manco-Johnson M J. Neonatal protein C: molecular composition and distribution in normal term infants. Thromb Res . 1989; 56 91-98
30 Schwarz H P, Muntean W, Watzke H, Richter B, Griffin J H. Low total protein S antigen but high protein S activity due to decreased C4b-binding protein in neonates. Blood . 1988; 71 562-565
31 Menashi S, Aurousseau M H, Gozin D. et al . High levels of circulating thrombomodulin in human foetuses and children. Thromb Haemost . 1999; 81 906-909
32 Weissbach G, Harenberg J, Wendisch J, Pargac N, Thomas K. Tissue factor pathway inhibitor in infants and children. Thromb Res . 1994; 73 441-446
33 Patel P, Weitz J, Brooker L A, Paes B, Mitchell L, Andrew M. Decreased thrombin activity of fibrin clots prepared in cord plasma compared with adult plasma. Pediatr Res . 1996; 39 826-830
34 Schmidt B, Ofosu F A, Mitchell L, Brooker L A, Andrew M. Anticoagulant effects of heparin in neonatal plasma. Pediatr Res . 1989; 25 405-408
35 Andrew M, Mitchell L, Vegh P, Ofosu F. Thrombin regulation in children differs from adults in the absence and presence of heparin. Thromb Haemost . 1994; 72 836-842
36 Chan A K, Berry L R, Monagle P T, Andrew M. Decreased concentrations of heparinoids are required to inhibit thrombin generation in plasma from newborns and children compared to plasma from adults due to reduced thrombin potential. Thromb Haemost . 2002; 87 606-613
37 Cvirn G, Gallistl S, Leschnik B, Muntean W. Low tissue factor pathway inhibitor (TFPI) together with low antithrombin allows sufficient thrombin generation in neonates. J Thromb Haemost . 2003; 1 263-268
38 Knöfler R, Hofmann S, Weissbach G. et al . Molecular markers of the endothelium, the coagulation, and the fibrinolytic systems in healthy newborns. Semin Thromb Hemost . 1998; 24 453-461
39 Ries M, Klinge J, Rauch R. Age-related reference values for activation markers of the coagulation and fibrinolytic systems in children. Thromb Res . 1997; 85 341-344