PMID- 12008942
OWN - NLM
STAT- MEDLINE
DCOM- 20030102
LR  - 20061115
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 87
IP  - 4
DP  - 2002 Apr
TI  - Decreased concentrations of heparinoids are required to inhibit thrombin 
      generation in plasma from newborns and children compared to plasma from adults 
      due to reduced thrombin potential.
PG  - 606-13
AB  - Thrombin generation is decreased and delayed in plasma from newborns and children 
      compared to adults. We hypothesized that lower doses of heparinoid anticoagulants 
      are required to give similar thrombin generation in newborn (umbilical cord) and 
      child plasmas compared to that of adults. Thrombin generation was performed in 
      either the absence or presence of unfractionated heparin (UFH), low molecular 
      weight heparin (LMWH) or a covalent antithrombin-heparin complex (ATH). After 
      contact activation and recalcification of each plasma, thrombin activity was 
      measured by periodic sub-sampling into chromogenic substrate. UFH inhibited 
      thrombin generation to a greater extent compared to LMWH in all plasmas. Cord 
      plasma was more sensitive to inhibition and displayed a greater difference in the 
      effectiveness of UFH compared to LMWH than other plasmas. Lower concentrations of 
      UFH and LMWH were required to inhibit thrombin generation in cord and child 
      plasmas compared to adult plasma. In comparison, ATH strongly inhibited thrombin 
      generation in all 3 plasmas. Similar peak thrombin concentrations were observed 
      at lower ATH concentrations (0.1 U/mL) compared to either UFH (0.25 U/mL) or LMWH 
      (0.25 U/mL). As with UFH and LMWH, cord plasma was more sensitive to inhibition 
      by ATH than the other plasmas and lower ATH concentrations inhibited thrombin 
      generation in cord and child plasmas compared to adult plasma. Decreased thrombin 
      generation with heparinoids in cord and child plasmas compared to adult plasma 
      coincided with decreased rates of prothrombin consumption and increased 
      proportion of thrombin-alpha2-macroglobulin inhibitor complexes. In summary, 
      lower doses of UFH, LMWH or ATH result in similar peak thrombin generation in 
      newborn and child plasmas compared to adult plasma. Cord plasma was the most 
      sensitive to inhibition, with ATH being more effective than UFH or LMWH.
FAU - Chan, Anthony K C
AU  - Chan AK
AD  - Hamilton Civic Hospitals Research Centre, Ontario, Canada. 
      achan@thrombosis.hhscr.org
FAU - Berry, Leslie R
AU  - Berry LR
FAU - Monagle, Paul T
AU  - Monagle PT
FAU - Andrew, Maureen
AU  - Andrew M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 9000-94-6 (Antithrombin III)
RN  - 9001-26-7 (Prothrombin)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
EIN - Thromb Haemost. 2002 Sep;88(3):14
MH  - Adolescent
MH  - Adult
MH  - Aging/*blood
MH  - Anticoagulants/administration & dosage/*pharmacology
MH  - Antithrombin III/administration & dosage/*pharmacology
MH  - Child
MH  - Child, Preschool
MH  - Dose-Response Relationship, Drug
MH  - Fetal Blood
MH  - Heparin/administration & dosage/*pharmacology
MH  - Heparin, Low-Molecular-Weight/administration & dosage/*pharmacology
MH  - Humans
MH  - Infant, Newborn
MH  - International Normalized Ratio
MH  - Partial Thromboplastin Time
MH  - Prothrombin/metabolism
MH  - Prothrombin Time
MH  - Reference Values
MH  - Thrombin/*biosynthesis
EDAT- 2002/05/15 10:00
MHDA- 2003/01/03 04:00
CRDT- 2002/05/15 10:00
PHST- 2002/05/15 10:00 [pubmed]
PHST- 2003/01/03 04:00 [medline]
PHST- 2002/05/15 10:00 [entrez]
PST - ppublish
SO  - Thromb Haemost. 2002 Apr;87(4):606-13.