Duke researchers suggest that use of a clotting agent commonly used after surgery should be restricted.
The scientists found that the agent known as bovine thrombin produced an immune response that led to lupus-like symptoms in genetically engineered mice after one dose. Lupus, an autoimmune disease in humans, causes behavioral abnormalities.
It is estimated that thrombin is used to control bleeding in over 500,000 surgical procedures annually, which researchers say represent about 5 percent of surgeries performed in the United States every year.
"Because [thrombin is] enzymatic and has biological activity, it can't be made chemically inert so its reactivity and antigenicity are carried with it," said lead investigator Dr. Jeffrey Lawson, assistant professor of surgery and pathology.
While it is still not clear if thrombin produces the same effects in humans as it did in mice, scientists are hoping these findings will shed light on the human risks of multiple exposures to thrombin.
During surgical procedures, the agent is applied directly to areas that need clotting. It works by cleaving molecules of fibrinogen, a process that ultimately converts blood from its fluid state into a solid one.
"As a surgeon you need a couple tricks in your bag, and that's why thrombin has been used. It's cheap, easy to use, and it works," Lawson said.
However, Lawson and his team found that subtle differences between the administered agent and human thrombin trigger an immune response in the body.
In January, researchers studied 150 heart surgery patients and found that more than 90 percent of those patients developed thrombin antibodies, and 30 percent developed antibodies that interacted with other human proteins.
These findings suggest autoimmune complications can increase significantly if a patient is exposed to thrombin more than once.
"Our immune systems are remarkably good about identifying things that are foreign. From our studies we have been able to demonstrate that nearly all people exposed to bovine thrombin develop an immune response to the agent and an increased risk of experiencing adverse clinical effects associated with re-exposure to the agent," Lawson said.
Some of the alternatives to thrombin that are currently available include non-human reagents and human thrombin derivatives. However, although these have been effective, many of them have not been clinically tested for their safety--a potential area for future research.
Furthermore, researchers believe these results will lead to better understanding of lupus.
"These findings represent an apparently unique cause of lupus. There have been a few studies that suggest that the enzymatic activity of thrombin can contribute to autoimmune disease," said investigator Jonathan Schoenecker, an M.D./Ph.D. graduate student. "[In this study] it appears that we might have caused autoimmunity by overloading the [immune] system with this enzyme. If we find that the [response] in our mice is caused by the enzymatic properties of thrombin, this could provide some important insight into autoimmunity."
Researchers also found that the female mice were especially susceptible to thrombin exposure. "We will have to do more research to see if the correlation we observed in the female mice is also evident in humans," said Rachel Johnson, a research technician who helped develop the animal model used in the study.
The findings were reported this month in the American Journal of Pathology.
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