Heparin Contaminant Confirmed

On April 23, 2008, researchers announced they had identified a chemical contaminating the blood-thinner Heparin from China, which confirmed previous FDA findings that it was oversulfated chondroitin sulfate. The investigators said they had used a standard analytical method to find the contamination, which had been difficult to pinpoint before, and said it might be used to screen other batches.

The tainted Heparin killed at least 81 patients and forced a widespread recall of the commonly used blood-thinner. It also caused a diplomatic squabble between U.S. and Chinese officials. "Given the nature of this contaminant, traditional screening tests cannot differentiate between affected and unaffected lots," Ram Sasisekharan of the Massachusetts Institute of Technology and colleagues wrote in the journal Nature Biotechnology.

"Our analysis suggests effective screening methods that can be used to determine whether or not Heparin lots contain the contaminant reported here."

Many patients in the United States and Europe who got the contaminated Heparin suffered immediate allergic reactions, with plummeting blood pressure, swelling of the larynx and other severe symptoms.

The researchers freeze-dried the Heparin and used a combination of nuclear magnetic resonance imaging and liquid chromatography-mass spectrometry to analyze its structure.

In addition to a known impurity of Heparin called dermatan sulfate, they found that contaminated lots contain a molecule that looks similar to Heparin and showed it was almost certainly oversulfated chondroitin sulfate.

Oversulfated chondroitin sulfate is derived from a popular supplement used to treat arthritis, among other things. It can resemble Heparin’s active ingredient but is much cheaper, leading some experts to suspect it was added deliberately.

"This study also provides a set of screening methods that could be used to monitor the Heparin supply and ensure the absence of oversulfated chondroitin sulfate contamination," they wrote.

In February 2008, Baxter International Inc. recalled most of its Heparin products, made with ingredients from China. Chinese officials said on April 21, 2008 they had tested batches of Heparin used by patients who reported health problems and only some of these batches contained the contaminant.

They said other contaminants; problems with the device used to inject the drug or health factors with the patients who used the drug could be to blame.

Heparin is made from pig intestines that are often collected from small, mostly unregulated farms in China. Baxter maintains the contamination occurred before the product reached Baxter or its raw ingredient supplier.

Democrats in the U.S. House of Representatives have accused the FDA of lax oversight in the case.