Author: Gerhard Cvirn

Source: Vascular Disease Prevention, Volume 1, Number 3, November 2004 , pp. 225-231(7)

Publisher: Bentham Science Publishers

Abstract:

Inhibition of exogenous thrombin is impaired in neonatal compared to normal adult plasma due to neonatal antithrombin (AT) deficiency. It has been suggested that newborn infants may be resistant to antithrombotic therapy [administration of unfractionated heparin (UH), low molecular weight heparin (LMWH), antithrombin-heparin complex (ATH)] during overt thrombotic disease when the neutralisation of abnormal thrombin activity is the therapeutic goal. The effects of anticoagulant drugs on de-novo thrombin generation in both cord and adult plasma are influenced by the type of plasma activation applied. In the presence of high amounts of initiator, as usual in conventional clotting assays, cord plasma is significantly more susceptible to addition of the anticoagulant drugs UH, LMWH, ATH, and recombinant human activated protein C (rhAPC) than adult plasma due to reduced neonatal thrombin potential. It can be speculated that lower doses of these anticoagulant drugs may be required to prevent de-novo thrombin generation and possibly thrombosis in newborn infants than in older patients. In contrast, in the presence of low amounts of lipidated tissue factor (TF) to trigger clot formation, probably simulating in-vivo conditions more closely than strong activation, cord plasma is significantly less susceptible to addition of rhAPC and possibly of other anticoagulant drugs. It has been shown that the low anticoagulant efficacy of rhAPC is attributable to the low neonatal levels of tissue factor pathway inhibitor (TFPI) and AT, resulting in concomitant low anticoagulant action of TFPI, AT, and rhAPC associated with efficient thrombin generation in neonates. From this point of view, higher doses of anticoagulant drugs may be required to prevent de-novo thrombin generation and possibly thrombosis in newborn infants than in older patients.

Keywords: cord and adult plasma; tissue factor pathway inhibitor; antithrombin; activated protein c; thrombomodulin; recombinant human activated protein c; thrombin generation; heparin

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1567270043404935

Affiliations: 1: Institute of Medical Chemistry and Pregl Laboratory, Medical University of Graz, Harrachgasse 21 / II, A-8010 Graz, Austria.

Publication date: 2004-11-01

More about this publication?

• Vascular Disease Prevention publishes reviews as well as original papers to update all those concerned with this topic at the clinical or scientific level. In addition to clinically relevant topics, we consider reviews and original papers dealing with the more scientific aspects of vascular disease prevention. This includes the evaluation of emerging vascular risk factors, research dealing with the pathogenesis of atherosclerosis and the investigation of new treatment options both at the clinical and scientific level (e.g. epidemiology, patient-based studies, experimental models, in vitro experiments or molecular research). Therefore, another function of Vascular Disease Prevention is to bridge the gap between clinical practice and ongoing laboratory-based research.
  
  In particular, we welcome critical reviews and comments on recent trials. This is a topic that requires regular updates because of the large number of trials published every year.
  
  Debates are encouraged in the correspondence section of this journal.
  The editorial structure of Vascular Disease Prevention is set up with the aim of dealing with the submitted material as rapidly as possible. Specialist editors will provide a more expert and rapid assessment unlike a more centralized editorial structure.

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