American Society of Hirudotherapy

Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants

Research article published in Molecules (Basel, Switzerland) (2019)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Research reportClinical LiteratureSafety & Infection ControlMendes A et al. · Molecules (Basel, Switzerland), 2019

Abstract

Nowadays, pharmaceutical heparin is purified from porcine and bovine intestinal mucosa. In the past decade there has been an ongoing concern about the safety of heparin, since in 2008, adverse effects associated with the presence of an oversulfated chondroitin sulfate (OSCS) were observed in preparations of pharmaceutical porcine heparin, which led to the death of patients, causing a global public health crisis. However, it has not been clarified whether OSCS has been added to the purified heparin preparation, or whether it has already been introduced during the production of the raw heparin. Using a combination of different analytical methods, we investigate both crude and final heparin products and we are able to demonstrate that the sulfated contaminants are intentionally introduced in the initial steps of heparin preparation. Furthermore, the results show that the oversulfated compounds are not structurally homogeneous. In addition, we show that these contaminants are able to bind to cells in using well known heparin binding sites. Together, the data highlights the importance of heparin quality control even at the initial stages of its production.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal Article
Indexed MeSH termsAnimalsAnticoagulantsCattleChondroitin SulfatesDrug ContaminationHeparinHeparin LyaseHumansHydrolysisIntestinal MucosaMagnetic Resonance SpectroscopyPolysaccharide-LyasesQuality ControlSwine

Summary

Analyses of crude and finished heparin show that structurally diverse oversulfated contaminants are intentionally introduced during the initial steps of heparin manufacture and can bind cells via known heparin-binding sites, highlighting the need for early-stage quality control.

Context

This study analyzed crude and final pharmaceutical heparin products to trace the origins of structurally diverse oversulfated contaminants, such as oversulfated chondroitin sulfate (OSCS), which previously caused adverse health events. The research is entirely focused on the quality control, manufacturing processes, and cellular binding properties of heparin derived from porcine and bovine intestinal mucosa. The article does not involve leeches, hirudotherapy, or leech-derived anticoagulants like hirudin.

Citation

Reference (Vancouver style)

Mendes A, Meneghetti MCZ, Palladino MV, Justo GZ, Sassaki GL, Fareed J, et al. Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants. Molecules. 2019;24(16):2988. doi:10.3390/molecules24162988. PMID: 31426507

Bibliographic details (authors, volume, pages, DOI) are taken from the PubMed record.

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

This website provides educational information and does not constitute medical advice, diagnosis, or treatment recommendations. Medicinal leech therapy carries clinically meaningful risks and should be performed only by qualified clinicians under institutionally approved protocols. FDA 510(k) clearance for medicinal leeches is limited to specific indications; investigational and off-label discussions are labeled accordingly. For patient-specific guidance, consult a qualified healthcare provider.