Scientists Show Chemical in Tainted Heparin Caused IllnessesApr 24, 2008 | Parker Waichman LLP
Scientist now know why contaminated heparin caused serious and sometimes fatal reactions in hundreds of patients. In a study published in the "New England Journal of Medicine", researchers say that pigs treated with tainted heparin have exhibited side effects similar to those seen in humans. The scientists also wrote that a test has been developed that can determine if heparin has been contaminated with the chemical causing the side effects.
The Food & Drug Administration (FDA) has linked tainted heparin with 81 deaths in the US, and hundreds of illnesses. Baxter International recalled nearly all its heparin injections in the U.S. after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC. Last week, FDA Commissioner Andrew von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
The New England Journal of Medicine study, led by researchers at MIT, offers the first potential link between the contaminant and the adverse reactions. The researchers found that the chondroitin sulfate activates two inflammatory pathways: one that initiates blood clotting and dilation of the blood vessels, and one that produces anaphylactic toxins. The first leads to a dangerous decrease in blood pressure, the second a serious allergic reaction. In blinded laboratory tests, the contaminated heparin activated the biological pathways, while normal heparin did not.
The researchers also said that regulators now have a test to detect contaminated heparin. Heparin consists of a long, complex chain of repeating sugar molecules. Oversulfated chondroitin sulfate, which is derived from animal cartilage, has a structure very similar to that of heparin and thus cannot be identified with the tests normally used to inspect batches of heparin. Traditional heparin safety screens test only for contaminants such as protein, lipids or DNA, and thus would not detect the presence of sugar chains that do not belong. The MIT research team played a key role in developing new technologies for analyzing complex sugars. Using the new technology, the research team was able to detect the presence of the faulty sugars.
According to The New York Times, the FDA has identified 12 Chinese companies that have supplied contaminated heparin to 11 countries — Australia, Canada, China, Denmark, France, Germany, Italy, Japan, the Netherlands, New Zealand and the United States. The FDA has not determined the original source of all the contamination or the points in the supply chain at which it was added. The Times also said officials have discovered tainted heparin lots that were manufactured as early as early as 2006, although a spike in illnesses associated with contaminated heparin began in November and persisted through February.