Kennedy Hodges, L.L.P. Legal Blog

Chicago Tribune reporter

The U.S. Food and Drug Administration, for the first time, has conclusively linked deaths of patients infused with the blood thinner heparin to a foreign substance found in specific lots of the drug made by Deerfield-based Baxter International Inc.

In an interview Tuesday with the Tribune, the FDA said it completed its review of 93 death reports related to heparin that the agency received from Jan. 1 to March 31, a period when there was a dramatic spike in potentially deadly allergic reactions from patients who had been injected with heparin. The popular blood thinner is used widely in large dosages, often before patients have dialysis or heart surgery.

Of 10 reports of death from severe shock known as anaphylaxis or hypotension, three of those could be traced to lot numbers of Baxter products that tested positive for an animallike substance known as oversulfated chondroitin sulfate. Heparin lot numbers were not known for the other seven deaths from anaphylaxis or hypotension, so the FDA could not determine whether those 7 patients received heparin contaminated with the substance.

"We have what looks like a cause and effect in some patients," Dr. Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, said in an interview, referring to the three deaths linked to contaminated heparin. "We know that they got contaminated heparin, and they died subsequently. This is one of the final links in the chain."

Baxter recalled its heparin products in February in the wake of the spike in the number of the allergic reactions. In recent months, federal health officials and Baxter believe the oversulfated chondroitin sulfate was intentionally put into the product from suppliers in China.

Baxter said it would not comment on the FDA's analysis, saying it has not been able to review it.

"We haven't seen this data and look forward to working with [the] FDA to understand this new information," said Baxter spokeswoman Erin Gardiner. "However, these findings appear to indicate what our own analysis has shown—that only a very small portion of the number of deaths reported seem to have a definitive link to heparin."

Before Baxter recalled and stopped producing heparin earlier this year, the company received heparin's active ingredient from Wisconsin-based Scientific Protein Laboratories, which manufactured the raw ingredients for Baxter's heparin at a plant in China. Scientific Protein's supply chain stretched through unregulated village workshops and farms in rural China. Heparin's active pharmaceutical ingredient is derived from pig intestines.

Earlier this year, the FDA tallied more than 90 reports of deaths and more than 1,000 adverse events associated with patients in the U.S. who had one or more allergic reactions to heparin products, including those sold by Baxter since Jan. 1, 2007.

After months of investigating 93 death reports from Jan. 1 to March 31, the agency Tuesday said it is able to give its most definitive evaluation. Of the remaining 83 reports, 13 were described as "potential complications of heparin use" such as bleeding; 25 cases were due to causes unrelated to heparin use such as pneumonia, sepsis and kidney failure.

"In the remaining 45 deaths, clinical information in the adverse-event reports is insufficient to specify the cause of death with clinical certainty," an FDA spokeswoman said. Woodcock added not enough information was given by providers or others who filled out the reports to make an adequate determination.

"While some of these [reports] appear definitely related [to contaminated heparin] many are still in the gray zone," Woodcock said. "We have looked over all of these death reports and a number of them were probably not related to the contaminated heparin."

Chinese health officials continue to question whether the problems may have originated elsewhere. The Chinese maintain the problems did not originate with active ingredient sourced in China despite analysis by FDA, Baxter and outside experts.