Development of selected coagulation factors and anticoagulants in preterm infants by the age of six months

Marjut Salonvaara; Pekka Riikonen; Elina Vahtera; Eija Mahlamäki; Kirsti Heinonen; Riitta Kekomäki

doi:10.1160/TH03-12-0769

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(04): 688-696
DOI: 10.1160/TH03-12-0769

Theme Issue Article

Schattauer GmbH

Development of selected coagulation factors and anticoagulants in preterm infants by the age of six months

Authors

Marjut Salonvaara

¹Department of Paediatrics, Kuopio University Hospital and Kuopio University, Kuopio, Finland
Pekka Riikonen

¹Department of Paediatrics, Kuopio University Hospital and Kuopio University, Kuopio, Finland
Elina Vahtera

²Finnish Red Cross Blood Service, Helsinki, Finland
Eija Mahlamäki

³Department of Clinical Chemistry, Kuopio University Hospital, Kuopio, Finland
Kirsti Heinonen

¹Department of Paediatrics, Kuopio University Hospital and Kuopio University, Kuopio, Finland
Riitta Kekomäki

²Finnish Red Cross Blood Service, Helsinki, Finland

Abstract

Summary

The development of the coagulation and anticoagulation system in preterm infants was assessed, with special emphasis on extremely low birth weight (ELBW) infants and haemorrhagic or other complications after birth. Coagulation factors II (prothrombin),V (FV),VII (FVII) and X (FX) were analysed at birth and at a corrected age of six months. In addition, antithrombin (AT), protein C (PC) and protein S (PS) were measured at six months, and DNA samples were tested for Factor V Leiden (R506Q). Eighty-two infants, with a median gestational age (GA) of 32 weeks (range 24–36) and a median birth weight of 1562 g (range 695–3520), were studied. Fifteen of these were ELBW infants (range 695-1000g). Prothrombin, FV, FVII and FX reached healthy term six-month-old infant activity levels. Prothrombin and FX did not reach adult values; median activity levels remained at 82% and 78%, respectively. During the follow up, the FV and FVII levels of the ELBW infants (GA 24-27 weeks) increased more than those of the preterm infants born with higher GA (p < 0.001). At birth, prothrombin correlated significantly with FV, FVII and FX (p < 0.001). FVII at birth and at six months correlated significantly with PC (p= 0.021 and p= 0.009, respectively). These findings indicate that the gain in the coagulation factor concentrations in infancy is greatest in infants with the lowest GA at birth. Interesting new inter-relations of coagulation factor and physiological anticoagulant levels may indicate that there are still unrecognised pathways in the function of newborn haemostasis.

Keywords

Prematurity - infant - coagulation factor - physiological anticoagulant - development

Full Text

References

References
1 Hathaway WE. The bleeding newborn. Semin Hematol 1975; 12: 175-88.
2 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72: 1651-57.
3 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the healthy full-term infant. Blood 1987; 70: 165-72.
4 Piecuch RE, Leonard CH, Cooper BA. et al. Outcome of extremely low birth weight infants (500 to 999 grams) over a 12-year period. Pediatrics 1997; 100: 633-9.
5 Forestier F, Daffos F, Galactéros F. et al. Hematological values of 163 normal fetuses between 18 and 30 weeks of gestation. Pediatr Res 1986; 20: 342-6.
6 Reverdiau-Moalic P, Delahousse B, Body G. et al. Evolution of blood coagulation activators and inhibitors in the healthy human fetus. Blood 1996; 88: 900-6.
7 Barnard D, Simmons M, Hathaway W. Coagulation studies in extremely premature infants. Pediatr Res 1979; 13: 1330-5.
8 Shankaran S, Bauer CR, Bain R. et al. Prenatal and perinatal risk and protective factors for neonatal intracranial hemorrhage. Arch Pediatr Adolesc Med 1996; 150: 491-7.
9 Mautone A, Girdano P, Montagna O. et al. Coagulation and fibrinolytic systems in the ill preterm newborn. Acta Paediatr 1997; 86: 1100-4.
10 Puckett RM, Offringa M. Prophylactic vitamin K for vitamin K deficiency bleeding in neonates (Cochrane Review). In: The Cochrane Library. Issue 1 2003. Oxford: Update Software.;
11 Crowther CA, Henderson-Smart DJ. Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage (Cochrane Review). In: The Cochrane Library. Issue 1 2001. Oxford: Update Software.;
12 Salonvaara M, Riikonen P, Kekomäki R. et al. Effects of gestational age and pre-and perinatal events on the coagulation status in premature infants. Arch Dis Child Fetal Ed 2003; 88: F324-F328.
13 Williams MD, Chalmers EA, Gibson BE. Guideline. The investigation and management of neonatal haemostasis and thrombosis. Br J Haematol 2002; 119: 295-309.
14 Kuhle S, Male C, Mitchell L. Developmental hemostasis: pro-and anticoagulant systems during childhood. Semin Thromb Hemost 2003; 29: 329-37.
15 Kühne T, Imbach P. Neonatal platelet physiology and patophysiology. Eur J Pediatr 1998; 157: 87-94.
16 Mann KG, Kalafatis M. Factor V: a combination of Dr Jekyll and Mr Hyde. Blood 2003; 101: 20-30.
17 Van Hylckama Vlieg A, Callas PW, Cushman M. et al. Inter-relation of coagulation factors and D-dimer levels in healthy individuals. J Thromb Haemost 2003; 01: 516-22.
18 Nicolaes GAF, Dahlbäck B. Factor V and thrombotic disease. Description of a Janus Faced Protein. Arterioscl Thromb Vasc Biol 2002; 22: 530-8.
19 Fair DS, Marlar RA. Biosynthesis and secretion of factor VII, protein C, protein S, and the protein C inhibitor from a human hepatoma cell line. Blood 1986; 67: 64-70.
20 Andrew M, Vegh P, Johnston M. et al. Maturation of the hemostatic system during childhood. Blood 1992; 80: 1998-2005.
21 Malm J, Bennhagen R, Holmberg L. et al. Plasma concentrations of C4b-binding protein and vitamin K-dependent protein S in term and preterm infants: low levels of protein SC4b-binding protein complexes. Br J Haematol 1988; 68: 445-9.
22 Sthoeger D, Nardi M, Karpatkin M. Protein S in the first year of life. Br J Haematol 1989; 72: 424-8.
23 Garcia de Frutos P, Mohammed RIAlim, Härdig Y. et al. Differential regulation of α and β chains of C4b-binding protein during acute-phase response resulting in stable plasma levels of free anticoagulant protein S. Blood 1994; 84: 815-22.