PMID- 20922518
OWN - NLM
STAT- MEDLINE
DCOM- 20110414
LR  - 20181201
IS  - 1618-2650 (Electronic)
IS  - 1618-2642 (Linking)
VI  - 399
IP  - 2
DP  - 2011 Jan
TI  - Protamine neutralisation of low molecular weight heparins and their 
      oligosaccharide components.
PG  - 763-71
LID - 10.1007/s00216-010-4220-8 [doi]
AB  - Protamine sulphate is an effective inhibitor of heparin and is used clinically to 
      neutralise both low molecular weight heparins (LMWH) and unfractionated heparin 
      (UFH). However, protamine sulphate does not fully counter the anti-Xa effect of 
      LMWH, even in excess (>40 mug to 1 IU/ml). To investigate the molecular basis for 
      this observation, the residual potencies in the presence and absence of plasma as 
      well as the molecular weight profiles of commercial LMWH neutralised with 
      increasing amounts of protamine were measured. Materials over 5000 Da are 
      preferentially neutralised by protamine. To further investigate this molecular 
      weight dependence, monodisperse oligosaccharides were prepared from three 
      commercial LMWHs. The specific anti-Xa activity for the fractions increased with 
      molecular weight, and was found to vary between the three preparations for 
      oligosaccharides of the same molecular weight. Our results indicate that 
      protamine sulphate neutralisation is largely dependent on molecular weight, 
      leading to the implication that LMWHs containing a larger proportion of small 
      oligosaccharides will not be as effectively neutralised. Protamine sulphate 
      neutralisation of any given LMWH is also affected by the specific anticoagulant 
      activities of its low molecular weight components, which varies between LMWH 
      products, presumably with the method of manufacture.
FAU - Schroeder, Mette
AU  - Schroeder M
AD  - LEO Pharma, Industriparken 55, 2750, Ballerup, Denmark.
FAU - Hogwood, John
AU  - Hogwood J
FAU - Gray, Elaine
AU  - Gray E
FAU - Mulloy, Barbara
AU  - Mulloy B
FAU - Hackett, Anne-Marie
AU  - Hackett AM
FAU - Johansen, Kristian B
AU  - Johansen KB
LA  - eng
PT  - Journal Article
DEP - 20101005
PL  - Germany
TA  - Anal Bioanal Chem
JT  - Analytical and bioanalytical chemistry
JID - 101134327
RN  - 0 (Anticoagulants)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Heparin Antagonists)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Oligosaccharides)
RN  - 0 (Protamines)
RN  - 7UQ7X4Y489 (Tinzaparin)
RN  - 9001-26-7 (Prothrombin)
RN  - 9002-04-4 (Factor IIa)
RN  - EC 3.4.21.6 (Factor Xa)
RN  - S79O08V79F (Dalteparin)
SB  - IM
MH  - Anticoagulants/*antagonists & inhibitors/*chemistry/metabolism
MH  - Dalteparin/antagonists & inhibitors/chemistry/metabolism
MH  - Factor Xa/metabolism
MH  - Factor Xa Inhibitors
MH  - Heparin Antagonists/*pharmacology
MH  - Heparin, Low-Molecular-Weight/*antagonists & inhibitors/*chemistry/metabolism
MH  - Humans
MH  - Molecular Weight
MH  - Oligosaccharides/antagonists & inhibitors/chemistry/metabolism
MH  - Partial Thromboplastin Time
MH  - Protamines/*pharmacology
MH  - Prothrombin/antagonists & inhibitors/metabolism
MH  - Tinzaparin
EDAT- 2010/10/06 06:00
MHDA- 2011/04/16 06:00
CRDT- 2010/10/06 06:00
PHST- 2010/08/06 00:00 [received]
PHST- 2010/09/12 00:00 [accepted]
PHST- 2010/09/09 00:00 [revised]
PHST- 2010/10/06 06:00 [entrez]
PHST- 2010/10/06 06:00 [pubmed]
PHST- 2011/04/16 06:00 [medline]
AID - 10.1007/s00216-010-4220-8 [doi]
PST - ppublish
SO  - Anal Bioanal Chem. 2011 Jan;399(2):763-71. doi: 10.1007/s00216-010-4220-8. Epub 
      2010 Oct 5.