Mechanisms responsible for the failure of protamine to inactivate low-molecular-weight heparin
Mechanisms responsible for the failure of protamine to inactivate low-molecular-weight heparin
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DOI：
10.1046/j.1365-2141.2002.03233.x
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发表时间：
2002-01-01
影响因子：
6.5
通讯作者：
Chan, AKC
中科院分区：
文献类型：
--
作者：
Crowther, MA;Berry, LR;Chan, AKC
Prolamine is unable to completely reverse the anticoagulant effect of the low-molecular-weight heparins (LMWH), a fact of clinical importance given the rapid increase in use of LMWH in clinical practice. This investigation sought to determine the mechanism by which LMWH were able to resist protamine-mediated inactivation. Affinity fractionation of LMWH by passage through a protamine column, with subsequent determination of molecular mass and sulphate charge density, demonstrated that the protamine-resistant fraction in LMWH is an ultra-low-molecular-weight fraction with low sulphate charge density. This group of molecules was not found in unfractionated heparin, even when species of similar molecular mass were compared, We then determined that different commercially available LMWH varied in their ability to be neutralized by protamine, and that this variability correlated with the total sulphate content of the LMWH, We conclude that reduced sulphate charge, not molecular mass, is the principle reason that protamine is unable to fully inactivate LMWH Furthermore, different LMWH vary in their ability to be neutralized by protamine, suggesting that product-specific recommendations for neutralization might be developed.
