Abstract
The risk of thromboembolic complications is considerably less for newborns and children than adults for any given insult, due to lower plasma concentrations of vitamin K-dependent coagulation factors, i.e., prothrombin, and contact factors [1, 2]. The capacity of newborn plasma to generate thrombin is decreased to 30–50% of adult values [3, 4]. In addition, alpha2-macroglobulin (α2-M) has been suggested as a major anticoagulant protein in infancy and has been demonstrated to complex up to 49% of generated alpha thrombin in newborn plasma [5, 6]. On the other hand, α2-M has been shown to bind activated protein C (APC) [7], one of the most important anticoagulant proteins. In addition, increased complex formation between α2-M and APC has been demonstrated to be associated with an unfavorable outcome in patients suffering from disseminated intravascular coagulation (DIC) [8], suggesting that α2-M might abrogate the anticoagulant action of APC. Previously, we have demonstrated a dose-dependent anticoagulant effect of APC in newborn and adult plasma using the determination of thrombin generation (thrombin potential, TP)
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, Powers P. Development of the human coagulation system in the fullterm infant. Blood 1987; 70: 165–170.
Andrew M. Developmental hemostasis: relevance to thromboembolic complications in pediatric patients. Thromb Haemost 1995; 74: 415–25.
Andrew M, Schmidt B, Mitchell L, Paes B, Ofosu F. Thrombin generation in newborn plasma is critically dependent on the concentration of prothrombin. Thromb Haemost 1990; 63: 27–30.
Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992; 8: 1998–2005.
Ling X, Delorme M, Berry L, Ofosu F, Mitchell L, Paes B, Andrew M. Alpha2-macroglobulin remains as important as antithrombin III for thrombin regulation in cord plasma in the presence of endothelial cell surfaces. Pediatr Res 1995; 37: 373–8.
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: 836–42.
Hoogendoorn H, Toh CH, Nesheim ME, Giles AR. Alpha 2-macroglobulin binds and inhibits activated protein C. Blood 1991; 78: 2283–90.
Scully MF, Toh CH, Hoogendoorn H, Manuel RP, Nesheim ME, Solymoss S, Giles AR. Activation of protein C and its distribution between its inhibitors protein C inhibitor, alpha 1-antitrypsin and alpha2-macroglobulin, in patients with disseminated intravascular coagulation. Thromb Haemost 1993; 69: 448–53.
Cvirn G, Gallistl S, Muntean W. Effects of antithrombin and protein C on thrombin generation in newborn and adult plasma. Thromb Res 1999; 93: 183–90.
Hemker HC, Willems GM, Beguin S. A computer assisted method to obtain the prothrombin activation velocity in whole plasma independent of thrombin decay processes. Thromb Haemost 1986; 56: 9–17.
Hemker HC, Wielders S, Kessels H, Beguin S. Continuous registration of thrombin generation in plasma, its use for the determination of the thrombin potential. Thromb Haemost 1993;70:617–24.
Hemker HC, Beguin S. Thrombin generation in plasma: its assessment via the endogenous thrombin potential. Thromb Hemost 1995; 74: 134–8.
Gallistl S, Muntean W, Leis HJ. Effects of heparin and hirudin on thrombin generation and platelet aggregation after intrinsic activation of platelet rich plasma. Thromb Haemost 1995; 74: 1163–8.
Wielders S, Mukherjee M, Michiels J, Rijkers DTS, Cambus JP, Knebel RWC, Kakkar V, Hemker HC. The routine determination of the endogenous thrombin potential, first results in different forms of hyper and hypocoagulability. Thromb Haemost 1997; 77: 629–36.
Kisiel W, Kondo S, Smith KJ, McMullen BA, Smith LF. Characterization of a protein C activator from Agkistrodon contortrix contortrix venom. J Biol Chem 1987; 262: 12607–13.
Svoboda P, Meier J, Freyvogel TA. Purification and characterization of three α2-antiplasmin and α2-macroglobulin inactivating enzymes from the venom of the Mexican coast rattlesnake (crotalus basiliscus). Toxicon 1995; 33: 1331–46.
Mitchell L, Piovella F, Ofosu F, Andrew M. Alpha2-macroglobulin may provide protection from thromboembolic events in antithrombin III-deficient children. Blood 1991; 78: 2299–304.
Massicote P, Leaker M, Marzinotto V, Adams M, Freedom R, Williams W, Vegh P, Berry L, Shah B, Andrew M. Enhanced thrombin regulation during warfarin therapy in children compared to adults. Thromb Haemost 1998; 80: 570–4.
Jolyon J. The kinetics of inhibition of α-thrombin in human plasma. J Biol Chem 1986; 261: 10313–8.
Dreyfus M, Magny JF, Bridey F, Schwarz HP, Planché C, Dehan M, Tchernia G. Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Engl J Med 1991; 325: 1565–8.
Rivard GE, David M, Farrell C, Schwarz HP. Treatment of purpura fulminans in meningococcemia with protein C concentrate. J Ped 1995; 126: 646–52.
David M, Andrew M. Venous thromboembolic complications in children. J Pediatr 1993; 123: 337–46.
Andrew M, David M, Adams M, Ali K, Anderson R, Barnard D, Bernstein M, Brisson L, Cairney B, De Sai D, Grant R, Israels S, Jardine L, Luke B, Massicote P, Silva M. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian registry of VTE. Blood 1994; 83: 1251–7.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Cvirn, G., Gallistl, S., Kutschera, J., Muntean, W. (2001). Anticoagulant Action of Activated Protein C is Diminished by Alpha2-Macroglobulin in Newborn Plasma. In: Scharrer, I., Schramm, W. (eds) 30th Hemophilia Symposium Hamburg 1999. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18240-2_10
Download citation
DOI: https://doi.org/10.1007/978-3-642-18240-2_10
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-67677-5
Online ISBN: 978-3-642-18240-2
eBook Packages: Springer Book Archive