Next Article in Journal
Synthesis and Antiproliferative Activity of Novel Heterocyclic Indole-Trimethoxyphenyl Conjugates
Next Article in Special Issue
Modernization of Enoxaparin Molecular Weight Determination Using Homogeneous Standards
Previous Article in Journal
Individual and Combined Effects of Engineered Peptides and Antibiotics on Pseudomonas aeruginosa Biofilms
Previous Article in Special Issue
The Good the Bad and the Ugly of Glycosaminoglycans in Tissue Engineering Applications
Article Menu
Issue 3 (September) cover image

Export Article

Open AccessArticle
Pharmaceuticals 2017, 10(3), 59;

Precipitation and Neutralization of Heparin from Different Sources by Protamine Sulfate

National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Herts EN6 3QG, UK
Institute for Pharmaceutical Sciences, King’s College London, 10 Stamford Street, London SE1 9HN, UK
Author to whom correspondence should be addressed.
Academic Editor: Jean Jacques Vanden Eynde
Received: 8 June 2017 / Revised: 28 June 2017 / Accepted: 29 June 2017 / Published: 2 July 2017
(This article belongs to the Special Issue Glycosaminoglycans and Proteoglycans)
Full-Text   |   PDF [1282 KB, uploaded 4 July 2017]   |  


Current therapeutic unfractionated heparin available in Europe and US is of porcine mucosal origin. There is now interest, specifically in the US, to use bovine mucosa as an additional source for the production of heparin. The anticoagulant action of heparin can be neutralized by protamine sulfate, and in this study the ability of protamine to bind and neutralize the anticoagulant activities of heparin from porcine mucosa, bovine mucosa and bovine lung were assessed. Protamine sulfate was able to bind and precipitate similar amounts of heparins from different sources on a mass basis. However, differential amounts of anticoagulant activities were neutralized by protamine sulfate, with neutralization of porcine mucosa more effective than for bovine lung and bovine mucosa. For all heparins, potentiation of thrombin inhibition by antithrombin and heparin cofactor II was preferentially neutralized over antithrombin-mediated inhibition of factor Xa or plasma clotting time. Whole blood thromboelastography showed that neutralization by protamine sulfate was more effective than the antithrombin dependent thrombin inhibition assays indicated. While there was no absolute correlation between average or peak molecular weight of heparin samples and neutralization of anticoagulant activity, correlation was observed between proportions of material with high affinity to antithrombin, specific activities and neutralization of activity. View Full-Text
Keywords: heparin; protamine sulfate; neutralization heparin; protamine sulfate; neutralization

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Hogwood, J.; Mulloy, B.; Gray, E. Precipitation and Neutralization of Heparin from Different Sources by Protamine Sulfate. Pharmaceuticals 2017, 10, 59.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Pharmaceuticals EISSN 1424-8247 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top