PMID- 16409456
OWN - NLM
STAT- MEDLINE
DCOM- 20060221
LR  - 20230829
IS  - 1538-7933 (Print)
IS  - 1538-7836 (Linking)
VI  - 4
IP  - 1
DP  - 2006 Jan
TI  - Fixed dosage of low-molecular-weight heparins causes large individual variation 
      in coagulability, only partly correlated to body weight.
PG  - 83-9
AB  - BACKGROUND: Low-molecular-weight heparins (LMWHs) are routinely given without the 
      control of their effect on coagulation. The endogenous thrombin potential (ETP) 
      is a sensitive detector of the heparin effect. QUESTION: What is the 
      interindividual variation in TG after a fixed dose of LMWH in normal volunteers, 
      is it explained by variation in weight? METHODS: Subcutaneous (s.c.) injection, 
      in 12 healthy volunteers, of 9000 aXa-units of unfractionated heparin (UFH) and 
      of three heparins with narrow MW distribution around 10.5, 6.0 and 4.5 kD. 
      Measurement of anti-thrombin (aIIa) and antifactor Xa (aXa)-activities and ETP at 
      11 time points over 24 h. RESULTS: The coefficient of variation (CV) of the AUCs 
      of aXa- and aIIa-activities is 50% for UFH and 22-37% for LMWHs. Because of the 
      hyperbolic form of the dose-response curve, the CV of the inhibition of the ETP 
      is lower: 32% for UFH and 13-21% for the LMWHs. Fixed dosage of LMWH caused 
      under-dosage in 10-13% of the samples and over-dosage in 5-11%. High or low 
      response is an individual property independent of the type of heparin injected 
      and only partially explained by variation in body weight. CONCLUSION: Optimized 
      individual dosage of LMWH is possible through recognition of high and low 
      responders, which requires one measurement of the heparin concentration or, 
      preferably, the heparin effect on the ETP, 2-5 h after a first injection.
FAU - Al Dieri, R
AU  - Al Dieri R
AD  - Synapse BV, Cardiovascular Research Institute, Maastricht, The Netherlands. 
      r.aldieri@thrombin.com
FAU - Alban, S
AU  - Alban S
FAU - Beguin, S
AU  - Beguin S
FAU - Hemker, H C
AU  - Hemker HC
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 9000-94-6 (Antithrombin III)
RN  - EC 3.4.21.6 (Factor Xa)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antithrombin III/analysis
MH  - Blood Coagulation/*drug effects
MH  - Blood Coagulation Tests
MH  - Body Weight/*physiology
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation
MH  - Factor Xa/analysis
MH  - Heparin, Low-Molecular-Weight/administration & 
      dosage/pharmacokinetics/*pharmacology
MH  - Humans
MH  - Male
MH  - Molecular Weight
MH  - Reproducibility of Results
MH  - Thrombophilia/chemically induced
EDAT- 2006/01/18 09:00
MHDA- 2006/02/24 09:00
CRDT- 2006/01/18 09:00
PHST- 2006/01/18 09:00 [pubmed]
PHST- 2006/02/24 09:00 [medline]
PHST- 2006/01/18 09:00 [entrez]
AID - S1538-7836(22)11027-5 [pii]
AID - 10.1111/j.1538-7836.2005.01672.x [doi]
PST - ppublish
SO  - J Thromb Haemost. 2006 Jan;4(1):83-9. doi: 10.1111/j.1538-7836.2005.01672.x.