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Thromb Haemost 2004; 91(05): 912-918
DOI: 10.1160/TH03-12-0739
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The anticoagulant action of recombinant human activated protein C (rhAPC, Drotrecogin α activated): comparison between cord and adult plasma

Gerhard Cvirn
1   Institute of Medical Chemistry and Pregl Laboratory, Medical University of Graz, Graz, Austria
2   Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Medical University of Graz, Graz, Austria
,
Siegfried Gallistl
3   Department of Pediatrics, Medical University of Graz, Graz, Austria
,
Martin Koestenberger
3   Department of Pediatrics, Medical University of Graz, Graz, Austria
,
Katrin Baier
2   Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Medical University of Graz, Graz, Austria
3   Department of Pediatrics, Medical University of Graz, Graz, Austria
,
Peter Fritsch
2   Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Medical University of Graz, Graz, Austria
3   Department of Pediatrics, Medical University of Graz, Graz, Austria
,
Joachim Greilberger
1   Institute of Medical Chemistry and Pregl Laboratory, Medical University of Graz, Graz, Austria
,
Günther Jürgens
1   Institute of Medical Chemistry and Pregl Laboratory, Medical University of Graz, Graz, Austria
,
Wolfgang Muntean
2   Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Medical University of Graz, Graz, Austria
3   Department of Pediatrics, Medical University of Graz, Graz, Austria
› Author AffiliationsFinancial support: This study was supported by grants from the “Gesellschaft zur Förderung der Gesundheit des Kindes (INVITA)” and the “Franz-Lanyar-Stiftung”.
Further Information

Publication History

Received 04 December 2003

Accepted after resubmission 18 February 2004

Publication Date:
01 December 2017 (online)

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Summary

The present study was performed to compare the anticoagulant efficiency of recombinant human activated protein C (rhAPC) in cord with that in adult plasma. RhAPC is a promising candidate to improve the outcome of severe sepsis. However, different anticoagulant efficiency of rhAPC in cord compared with adult plasma has to be expected due to physiological low plasma levels of tissue factor pathway inhibitor (TFPI) and antithrombin (AT) present in neonates, two inhibitors known to markedly influence the anticoagulant action of APC. Clot formation was induced in our experiments by addition of high (30 µM) or low (20 pM) amounts of lipidated tissue factor (TF). High amounts of TF are conventionally applied in standard clotting assays, whereas plasma activation with low amounts of TF probably better matches the conditions in vivo. We demonstrate that under low coagulant challenge increasing amounts of rhAPC (0.1 – 0.5 µg/ml final plasma concentration) dose-dependently prolonged clotting time and suppressed thrombin potential and prothrombin fragment 1 + 2 generation in both cord and adult plasma. The same was true for experiments performed under high coagulant challenge when 4 – 16 µg/ml of rhAPC were added. Whereby, cord plasma was significantly more susceptible to addition of rhAPC in the presence of high amounts of TF and adult plasma was significantly more susceptible to addition of rhAPC in the presence of low amounts of TF. We demonstrate that increased anticoagulant efficiency of rhAPC in adult plasma under low coagulant challenge is attributable to the physiological high levels of TFPI and AT present in adults.

Keywords

Recombinant human activated protein C - tissue factor pathway inhibitor - antithrombin - tissue factor - thrombin potential - cord and adult plasma
 

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