The in vitro anticoagulant effects of danaparoid, fondaparinux, and lepirudin in children compared to adults.
BACKGROUND
Major physiological differences in the coagulation system of children compared to that of adults are well documented. We have previously investigated the age-related differences in response to Unfractionated Heparin (UFH). However, the impact of developmental haemostasis on more recent anticoagulant drugs is unknown. A number of these drugs are approved for use in specific indications in adults and none are approved for use in children. This study aimed to determine whether age-related differences in effect and impact on monitoring tests exist in vitro for danaparoid, fondaparinux and lepirudin.


METHODS
Plasma samples were obtained from healthy children and pooled into age-specific pools, in order to obtain sufficient quantity of plasma required for the analysis of the three drugs. Each age-specific pool was spiked with different concentrations of danaparoid, fondaparinux and lepirudin and response was measured using standard techniques. All experiments were repeated using three separate plasma pools. The effect of each drug in children's plasma was compared to the effect in the respective adult plasma pool.


RESULTS
Age-related differences in effect on thrombin potential and monitoring tests were observed only with the drug lepirudin. Specifically, APTT for children up to 5 years of age was increased compared to adults; all children had lower ECT results compared to adults; children up to 10 years of age had increased inhibition of ETP as compared to adults.


CONCLUSIONS
This study confirms age-related differences in response to anticoagulants with predominant anti-IIa effect and highlights the need for further research into this area.
Ignjatovic
Vera
V
Department of Clinical Haematology, Royal Children's Hospital, Melbourne, Australia. verai@unimelb.edu.au
Summerhayes
Robyn
R
Yip
Yan Yan
YY
Monagle
Paul
P
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D003871:Dermatan Sulfate / Q000494:pharmacology*; D000077425:Fondaparinux; D006497:Heparan Sulfate / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D010314:Partial Thromboplastin Time; D011134:Polysaccharides / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014914:Whole Blood Coagulation Time
D000925:Anticoagulants; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D000077425:Fondaparinux; D006497:Heparan Sulfate; D006629:Hirudins; D011134:Polysaccharides; D011994:Recombinant Proteins; C035838:danaparoid; C083544:lepirudin