Biological and structural analyses of bovine heparin fractions of intermediate and high molecular weight

Research output: Contribution to journalArticle

  • Authors:
  • Alexsandro V Nogueira
  • Daiana L Drehmer
  • Marcello Iacomini
  • Guilherme L Sassaki
  • Thales R Cipriani

Abstract

Low molecular weight heparin, which is generally obtained by chemical and enzymatic depolymerization of unfractionated heparin, has high bioavailability and can be subcutaneously injected. The aim of the present investigation was to fractionate bovine heparin using a physical method (ultrafiltration through a 10kDa cut-off membrane), avoiding structural modifications that can be caused by chemical or enzymatic treatments. Two fractions with different molecular weights were obtained: the first had an intermediate molecular weight (B-IMWH; Mn=9587Da) and the other had a high molecular weight (B-HMWH; 22,396Da). B-IMWH and B-HMWH have anticoagulant activity of 103 and 154IU/mg respectively, which could be inhibited by protamine. Both fractions inhibited α-thrombin and factor Xa in vitro and showed antithrombotic effect in vivo. Moreover, ex vivo aPTT assay demonstrated that B-IMWH is absorbed by subcutaneous route. The results showed that ultrafiltration can be used to obtain two bovine heparin fractions, which differ on their molecular weights, structural components, anticoagulant potency, and administration routes.

Bibliographical metadata

Original languageEnglish
Pages (from-to)72-78
Number of pages7
JournalCarbohydrate Polymers
Volume157
Early online date20 Sep 2016
DOIs
Publication statusPublished - 10 Feb 2017