Topical thrombin has been used for decades to control minor surgical bleeding, and is used in > 1 million surgical procedures in the United States annually. Initially, topical thrombin was derived from human plasma but concerns over blood-borne pathogens led to widespread use of thrombin from bovine (cattle) plasma by the 1980s. Subsequent reports suggested that antibodies generated by exposure to bovine thrombin cross-react with human clotting factors and cause rare bleeding or clotting abnormalities. This led to the reintroduction of a highly purified human plasma-derived thrombin in 2007 aimed at reducing the risk of pathogenicity. In 2008, recombinant human thrombin was approved, which claimed to reduce the risks of viral exposure associated with human plasma and immunogenicity related to bovine plasma. In 2008, a new, more highly purified version of
bovine thrombin was also introduced.