Harvard-MIT scientists unlock chemical and biological secrets of tainted heparin

In two separate reports yesterday, two international teams led by Ram Sasisekharan of the Harvard-MIT Division of Health Sciences and Technology offered insights into the contamination of the blood-thinner heparin that has been linked to 81 deaths since November.

How the contaminant entered the manufacturing process is still a mystery, but the researchers have confirmed the identity of the chemical culprit, and explained why it eluded detection, and how it caused serious reactions in so many people. Patients typically need the drug to prevent blood clots while they undergo kidney dialysis or cardiac surgery. The main ingredient for heparin, which is manufactured in China, is derived from pig intestines.

In one paper, Sasisekharan’s team confirmed that the contaminant is a complex sugar known as oversulfated chondroitin sulfate, and showed why its chemical structure made it particularly difficult to detect. The report appears in Nature Biotechnology.

The second team showed the biological link between the contaminant and the symptoms reported in patients who received it. They demonstrated in laboratory samples and in pigs how the contaminant triggered an allergic-like immune response and lowered blood pressure. Patients who suffered bad reactions after receiving the tainted heparin had extremely low blood pressure, shortness of breath, nausea, and swelling of the skin and mucous membranes. This work is described in the New England Journal of Medicine.

Both teams included researchers from Momenta Pharmaceuticals in Cambridge, which makes products that analyze complex mixtures. Sasisekharan receives consulting fees from Momenta.