Oversulfated Chondroitin Sulfate Bioassay Developed to Protect Heparin Supplies

A simple in-vitro bioassay for the heparin contaminant oversulfated chondroitin sulfate (OSCS), in addition to procedures currently in place, will help in securing the global supply chain for heparin and reduce the risk of patients being exposed to harmful contaminants.

Testing of heparin products before the contamination (that caused a large number of allergic reactions and a number of fatal cases) did not check for molecules of a similar structure to OSCS, which, like heparin, is composed of a long complex chain of repeating sugar molecules. Rogue proteins, lipids, and DNA were checked for but there was no test for sugar contaminants.

Publications dated April 23, 2008, in the online editions of Nature Biotechnology and The New England Journal of Medicine (NEJM) provided clear evidence of the effects of the heparin contaminant OSCS in the body, and critically identified a way to improve its detection.

A team of scientists from the U.S. National Institute of General Medical Science (NIGMS; Bethesda, MD, USA) showed that OSCS activates two inflammatory pathways. One of these pathways dilates blood vessels and initiates blood clotting and the other pathway causes anaphylactic toxins to be produced. Heparin contaminated with OSCS was shown to initiate these pathways whereas normal heparin did not.

The first pathway results in the victim's blood pressure dropping dramatically. The second induces a serious allergic reaction, which was manifested as profound hypotensive response in the pigs used in the study. These responses match those witnessed in humans.

The scientific team reported that they could rapidly identify a contaminant, quantify its levels, and then finally characterize the compound. Implementation of these processes should help protect against the effects of any future contaminations.

Ram Sasisekharan, senior author of the articles said, "Sophisticated analytical techniques enabled complete characterization of the contaminant present in heparin. Further, this study also provides the scientific groundwork for critical improvements in screening practices that can now be applied to monitor heparin, thus ensuring patient safety.”


Related Links:
U.S. National Institute of General Medical Science