Age-related differences in heparin response.
BACKGROUND
Major physiological differences in the coagulation system throughout childhood, compared to adults, are well documented. However, the impact of this on anticoagulant drugs is unknown. This study aimed to determine whether heparin therapeutic range determination is affected by the age of plasma donors and whether age-specific therapeutic ranges for heparin therapy may need to be considered in the clinical setting.


METHODS
Plasma samples were obtained from healthy children and adults, and pooled into age-specific pools. These were spiked with different concentrations of heparin and APTT; Anti-Factor Xa and Anti-Factor IIa were measured using standard techniques. The experiments were repeated using three separate plasma pools, and results expressed as means with standard deviations.


CONCLUSIONS
The results show clear age-related differences in APTT for the same Anti-Factor Xa heparin concentration. The differences were more pronounced in younger children, with higher APTT for same Anti-Factor Xa. The Anti-Factor IIa activity of heparin for a given Anti-Factor Xa activity also differed between age-specific plasma pools. This study suggests that when using heparin in children, basic assumptions about the drug mechanism of action and implications for therapeutic ranges need to be considered.
Ignjatovic
Vera
V
Department of Haematology, Royal Children's Hospital, Flemington Road, Parkville 3052, Victoria, Australia. verai@unimelb.edu.au
Furmedge
Janine
J
Newall
Fiona
F
Chan
Anthony
A
Berry
Leslie
L
Fong
Chrystal
C
Cheng
Ken
K
Monagle
Paul
P
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000990:Antithrombin III / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D015951:Factor Xa / Q000187:drug effects; D006493:Heparin / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000187:drug effects; D015912:Thrombolytic Therapy / Q000009:adverse effects*
D000990:Antithrombin III; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D015951:Factor Xa