Low molecular weight protamine (LMWP) as nontoxic heparin/low molecular weight heparin antidote (II): In vitro evaluation of efficacy and toxicity

Li Chien Chang, Jun Feng Liang, Hsiao Feng Lee, Lai Ming Lee, Victor C. Yang

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Patients undergoing anticoagulation with heparin or low molecular weight heparin (LMWH) require a superior antidote that possesses more selective biological actions and a better safety profile than protamine. We had previously developed 2 low molecular weight protamine (LMWP) fractions (TDSP4 and TDSP5) from thermolysin-digested protamine as potential nontoxic, heparin-neutralizing agents. In this, the second article in this series, studies focused on in vitro evaluation of heparin/LMWH-neutralizing efficacy and putative toxicity. These LMWP fractions, particularly TDSP5, were effective and fully capable of neutralizing a broad spectrum of heparin-induced anticoagulant activities (ie, aPTT, anti-Xa, and anti-IIa activities). Additionally, these LMWP fractions could neutralize the activities of commercial LMWH. As assessed by the anti-Xa assay, TDSP5 was as effective as, although less potent than, protamine in reversing the activity of Mono-Embolex (molecular weight 5000-7000) and 2 other different sizes (molecular weight of 3000 and 5000 d) of LMWH preparations. Furthermore, compared with protamine, TDSP5 exhibited a much-reduced toxicity and thus an improved safety profile, as reflected by its reduced ability to activate the complement system and cross-react with the antiprotamine antibodies, which are 2 primary indices of protamine toxicity.

Original languageEnglish
JournalAAPS PharmSci
Volume3
Issue number3
DOIs
StatePublished - 2001

Keywords

  • Activation
  • Anti-Xa assay
  • Complement
  • Cross-reactivity
  • Heparin/LMWH
  • Immunogenicity
  • Neutralization
  • Protamine toxicity
  • aPTT clotting assay

Fingerprint

Dive into the research topics of 'Low molecular weight protamine (LMWP) as nontoxic heparin/low molecular weight heparin antidote (II): In vitro evaluation of efficacy and toxicity'. Together they form a unique fingerprint.

Cite this