Hamostaseologie 2008; 28(S 01): S61-S66
DOI: 10.1055/s-0037-1617119
Original article
Schattauer GmbH

Thrombin generation in paediatric patients with congenital heart disease[*]

Determination by calibrated automated thrombographyThrombinbildung bei Kindern mit angeborenem HerzfehlerBestimmung durch kalibrierte automatisierte Thrombographie
M. Koestenberger
1   Division of Pediatric Cardiology, Department of Pediatrics
,
G. Cvirn
2   Institute of Physiological Chemistry, Centre of Physiological Medicine
,
A. Rosenkranz
3   Department of Pediatrics, Medical University Graz, Austria
,
B. Leschnik
3   Department of Pediatrics, Medical University Graz, Austria
,
W. Raith
3   Department of Pediatrics, Medical University Graz, Austria
,
W. Muntean
3   Department of Pediatrics, Medical University Graz, Austria
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
30. Dezember 2017 (online)

Summary

Thrombin generation was studied in paediatric patients with congenital heart disease (CHD) undergoing cardiac surgery using the calibrated automated thrombography (CAT) in terms of the lag time until the onset of thrombin formation, time to thrombin peak maximum (TTP), endogenous thrombin potential (ETP), and thrombin peak height. The suitability to determine the coagulation status of these patients was investigated. Patients, material, methods: CAT data of 40 patients with CHD (age range from newborn to 18 years) were compared to data using standard coagulation parameters such as prothrombin (FII), antithrombin (AT), tissue factor pathway inhibitor (TFPI), prothrombin fragment 1.2 (F 1.2), thrombin-antithrombin (TAT), activated partial thromboplastin time (aPTT), and prothrombin time (PT). Results: A significant positive correlation was seen between ETP and FII (p < 0.01; r = 0.369), as well as between peak height and F II (p < 0.01; r = 0.483). A significant negative correlation was seen between ETP and TFPI values (p < 0.05; r = –0.225) while no significant correlation was seen between peak height and TFPI. A significant negative correlation was seen between F 1.2 generation and ETP (p < 0.05; r = –0.254) and between F 1.2 generation and peak height (p < 0.05; r = –0.236). No correlation was seen between AT and ETP or peak. Conclusions: CAT is a good global test reflecting procoagulatory and inhibitory factors of the haemostatic system in paediatric patients with CHD.

Zusammenfassung

Wir untersuchten die Thrombinentstehung bei Kindern mit angeborenen Herzfehlern rund um Herzoperation, um den Einsatz eines neuen Gerätes (CAT) zu evaluieren, das eine automatische Dokumentation der Thrombinentstehung ermöglicht. Marker sind die Gerinnungszeit bis zum Eintreten der Thrombinentstehung, die Zeit bis zum Thrombinmaximum (TTP), das endogene Thrombinpotential (ETP) und die maximale Höhe des Thrombinbursts. Patienten, Material, Methoden: Wir untersuchten 40 Kinder mit angeborenen Herzfehlern vom Neugeborenen- bis ins Jugendalter. Unsere CAT-Daten haben wir verglichen mit Messgrößen wie FII, AT, F 1.2, TFPI und aPTT. Ergebnisse: Wir fanden eine positive Korrelation zwischen ETP und FII sowie zwischen der maximalen Höhe des Thrombinbursts und FII. Eine negative Korrelation zeigte sich zwischen ETP und TFPI, zwischen F 1.2 und ETP sowie zwischen F 1.2 und maximaler Höhe des Thrombinbursts. Keine Korrelation sahen wir zwischen TFPI und maximaler Höhe des Thrombinbursts sowie zwischen AT und ETP. Schlussfolgerung: Das neue CAT spiegelt die pro- und antikoagulatorischen Faktoren des Gerinnungssystems bei Kindern mit angeborenen Herzfehlern gut wider. Es eignet sich daher als globaler Test.

* All authors have made substantial contributions to the conception and design of the study, to the acquisition of data or to the analysis and interpretation of data.


 
  • References

  • 1 Guzzetta N, Miller B, Todd K. et al. Clinical measures of heparin´s effect and thrombin inhibitor levels in pediatric patients with congenital heart disease. Anesth Analg 2006; 103: 1131-1138.
  • 2 Hemker HC, Beguin S. Phenotyping the clotting system. Thromb Haemost 2000; 84: 747-751.
  • 3 Dietrich W. Reducing thrombin formation during cardiopulmonary bypass: is there a benefit of the additional anticoagulant action of aprotinin?. J Cardiovasc Pharmacol 1996; 27: S50-S57.
  • 4 Boisclair M, Lane D, Philippou H. et al. Thrombin production, inactivation and expression during open heart surgery measured by assays for activation fragments including a new ELISA for prothrombin fragment F 1+2. Thromb Haemost 1993; 70: 253-258.
  • 5 Petaja J, Peltola K, Sairanen H. et al. Fibrinolysis, antithrombin III, and protein C in neonates during cardiac operations. J Thorac Cardiovasc Surg 1996; 112: 665-671.
  • 6 Jahangiri M, Kreutzer J, Zurakowski D. et al. Evaluation of hemostatic and coagulation factor abnormalities in patients undergoing the Fontan operation. J Thorac Cardiovasc Surg 2000; 120: 778-782.
  • 7 Mann KG, Brummel K, Butenas S. What is all that thrombin for?. J Thromb Haemost 2003; 1: 1504-1514.
  • 8 Hemker HC, Giesen P, Al Dieri R. et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemo Thromb 2003; 33: 4-15.
  • 9 Butenas S, Van’t Veer C, Mann KG. ‘Normal’ thrombin generation. Blood 1999; 94: 2169-2178.
  • 10 Sorensen B, Johansen P, Christiansen K. et al. Whole blood coagulation thrombelastographic profiles employing minimal tissue factor activation. J Thromb Haemost 2003; 1: 551-558.
  • 11 Cvirn G, Gallistl S, Koestenberger M. et al. The anticoagulant action of recombinant human activated protein C (rhAPC, Drotrecogin alpha activated): comparison between cord and adult plasma. Thromb Haemost 2004; 91: 912-918.
  • 12 Hemker HC, Giesen P, Al Dieri R. et al. The Calibrated Automated Thrombogram (CAT): a universal routine test for hyper- and hypocoagulability. Pathophysiol Haemo Thromb 2002; 32: 249-253.
  • 13 Nowak-Göttl U, Kotthoff S, Hagemeyer E. et al. Interaction of fibrinolysis and prothrombotic risk factors in neonates, infants, and children with and without thromboembolism and underlying cardiac disease. a prospective cohort study. Thromb Res 2001; 103: 93-101.
  • 14 Ozbek N, Atac F, Yildirim S. et al. Analysis of prothrombotic mutations and polymorphisms in children who developed thrombosis in the perioperative period of congenital cardiac surgery. Cardiol Young 2005; 15: 19-25.
  • 15 Heying R, van Oeveren W, Wilhelm S. et al. Children undergoing cardiac surgery for complex cardiac defects show imbalance between pro- and anti-thrombotic activity. Critical Care 2006; 10: R165.
  • 16 Davie EW, Fujikawa K, Kisiel W. The coagulation cascade: Initiation, maintenance and regulation. Biochemistry 1991; 30: 10363-10370.
  • 17 Cvirn G, Gallistl S, Leschnik B. et al. Low tissue factor pathway inhibitor together with low antithrombin allows sufficient thrombin generation in the neonate. J Thromb Haemost 2003; 1: 263-268.
  • 18 Cvirn G, Gallistl S, Rehak T. et al. Elevated thrombin- forming capacity of tissue factor-activated cord compared with adult plasma. J Thromb Haemost 2003; 1: 1785-1790.
  • 19 Cvirn G, Koestenberger M, Leschnik B. et al. Protein S modulates the anticoagulant action of recombinant human activated protein C: a comparison between neonates and adults. Brit J Pharmacol 2005; 146: 1082-1086.
  • 20 Hemker HC, Al Dieri R, Beguin S. Thrombin generation assays: accruing clinical relevance. Curr Opin Hematol 2004; 11: 170-175.
  • 21 Regnault V, Hemker HC, Wahl D. et al. Phenotyping the haemostatic system by thrombography-potential for the estimation of thrombotic risk. Thromb Res 2004; 114: 539-545.
  • 22 Hemker HC, Beguin S. Thrombin generation in plasma: its assessment via the endogenous thrombin potential. Thromb Haemost 1995; 74: 134-138.
  • 23 Cimenti C, Mangge H, Haidl H. et al. Thrombin generation in severely obese children. J Thromb Haemost 2006; 4: 1834-1836.
  • 24 Haidl H, Cimenti C, Leschnik B. et al. Age-dependency of thrombin generation measurements by means of calibrated automated thrombography (CAT). Thromb Haemost 2006; 95: 772-775.
  • 25 Kuhle S, Male C, Mitchell L. Developmental hemostasis: pro- and anticoagulant systems during childhood. Semin Thromb Hemost 2003; 29: 329-337.
  • 26 Owings J, Pollock M, Gosselin R. et al. Anticoagulation of children undergoing cardiopulmonary bypass is overestimated by current monitoring techniques. Arch Surg 2000; 135: 1042-1047.
  • 27 Kyrle P, Brockmeier J, Weltermann A. et al. Inhibition rather than enhancement of hemostatic system activation during initiation of oral anticoagulant treatment. Thromb Haemost 1997; 77: 685-689.