Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Anal Bioanal Chem ; 399(2): 763-71, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20922518

ABSTRACT

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 µg 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.


Subject(s)
Anticoagulants/antagonists & inhibitors , Anticoagulants/chemistry , Heparin Antagonists/pharmacology , Heparin, Low-Molecular-Weight/antagonists & inhibitors , Heparin, Low-Molecular-Weight/chemistry , Protamines/pharmacology , Anticoagulants/metabolism , Dalteparin/antagonists & inhibitors , Dalteparin/chemistry , Dalteparin/metabolism , Factor Xa/metabolism , Factor Xa Inhibitors , Heparin, Low-Molecular-Weight/metabolism , Humans , Molecular Weight , Oligosaccharides/antagonists & inhibitors , Oligosaccharides/chemistry , Oligosaccharides/metabolism , Partial Thromboplastin Time , Prothrombin/antagonists & inhibitors , Prothrombin/metabolism , Tinzaparin
SELECTION OF CITATIONS
SEARCH DETAIL
...