Baxter Healthcare has temporarily stopped making its multiple-dose vials of heparin sodium following reports of serious allergic reactions and possibly four patient deaths.

Derived from pig intestines, heparin has been sold in the U.S. since the 1930s. The intravenous medication has helped millions of patients benefit by avoiding potentially life-threatening blood clots in arteries, veins and lungs. It also generates about $30 million in annual sales for Baxter. The Deerfield-based company reported $11.3 billion in total revenue for 2007.

The U.S. Food and Drug Administration said it had received about 350 reports of health problems associated with Baxter’s injectable heparin product since the end of 2007. Dr. John Jenkins, director of the U.S. Food and Drug Administration Office of New Drugs at the Center for Drug Evaluation and Research, said during a Monday teleconference that there were less than 100 reports of adverse reactions in all of 2007, Forbes reported.

The problems occurred primarily in patients undergoing kidney dialysis and heart surgery. Four patients died, but the relationship to the drug is unclear.

“While we have reports of four deaths at this time, it is not possible to establish a relationship between the deaths and the use of heparin. To date, a cause to the adverse events has not been identified,” Jenkins said.

Adverse reactions included difficulty breathing, nausea or vomiting, excessive sweating and falling blood pressure, which can lead to life-threatening shock. These reactions have been seen with as few as several 1000 units per milliliter of heparin, and as much as 50,000 units per milliliter, Jenkins said.

The Missouri Department of Health and Senior Services, which had seen several cases in one pediatric hospital starting in November, first reported the problem to the U.S. Centers for Disease Control and Prevention in January.

Following the reports, Baxter started a voluntary recall of the affected lots of heparin Jan. 17, but adverse reactions have been found in other lots of Baxter’s multi-dose heparin. This led the company to suspend Heparin’s production Monday.

“FDA is currently collaborating with Baxter, the CDC and other experts to determine the root cause of the serious adverse events. Investigators and scientists are conducting inspections of all facilities and processes involved in the manufacture of Baxter’s heparin. FDA investigators and scientists are also conducting tests of samples of Baxter’s products,” Jenkins said.

Heparin is a “medical necessity” and a recall would have caused a severe shortage.

“The FDA is working with other manufacturers of heparin to fill the void that will occur if the Baxter manufacturing suspension continues,” Jenkins said.

More than one million multiple-dose vials of heparin are sold each month in the U.S.

“Given the widespread use of this critical anticoagulant (frequently called a blood thinner) and the impact a product shortage would have on operating rooms, dialysis centers and other critical care areas, the removal of Baxter's heparin from the market would create more risk to the population of patients requiring heparin therapy than the increased potential for experiencing an adverse reaction,” said a statement released Monday by Baxter.

Until the cause of the adverse reactions is known, the FDA is urging doctors to use the lowest possible dose, infuse it slowly, monitor patients closely, and consider administering steroids or antihistamines before heparin.

“There is going to be a shortage problem in the immediate and long-term future with the suspension of Baxter’s manufacturing. Facilities and physicians will have to decide immediately what they do with the heparin on hand, and they’ll have to start looking for heparin for the long term,” Dr. Jenkins said.