Abstract
It has been reported that patients exposed to topical bovine thrombin preparations may develop antibodies against bovine thrombin, factr V or various other proteins found in these preparations. Such antibodies can cross-react with human endogenous coagulation proteins and may lead to alterations in the coagulation laboratory parameters, hypersensitivity reactions, and severe bleeding or thrombosis. The underlying mechanisms for the coagulopathy are not fully understood yet. To better understand the cross-reactivity of anti-bovine thrombin antibodies with human corresponding coagulation proteins, bovine crude thrombin, and its purified versions, thrombin 4A (the old version of Thrombin-JMI before year 2008) and thrombin 4B (the current version of Thrombin-JMI on market), were used to generate relevant anti-bovine thrombin immunoglobulin G (IgGs) in rabbits. Using Western blotting, the cross-reactivity of each IgG with human alpha-thrombin and a recombinant version of human thrombin (Recothrom) was investigated. The results indicated that no cross-reactivity with either human alpha-thrombin or Recothrom was observed with both anti-bovine crude thrombin IgGs and thrombin 4B IgGs. However, anti-bovine thrombin 4A IgGs showed apparent cross-reactivity with human alpha-thrombin and Recothrom in a protein amount-dependent manner. Furthermore, the results revealed that the cross-reactivity of anti-bovine thrombin 4A IgGs with human alpha-thrombin and Recothrom was immunization time-dependent. The minimum concentration of 4A IgG required to exhibit cross-reactivity with human alpha-thrombin and Recothrom varied considerably among individual rabbits. These results indicate that rabbit anti-bovine thrombin IgGs can cross-react with human alpha-thrombin and Recothrom, suggesting that human antibodies against bovine thrombin may also cross-react with human recombinant thrombin. Thus, the patients who were previously exposed to bovine thrombin may also develop antibodies which can cross-react with human recombinant thrombin.
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