Cross Reactivity of Human Recombinant thrombin (Recothrombin) to Antibovine Thrombin Antibodies. Clinical Implications

Abstract

Bovine thrombin preparations are widely used topical hemostatic agents. Whereas older bovine thrombin preparations were reported to produce immunologic responses upon repeated exposure, the newly introduced recombinant human thrombin preparation (Zymogenetics, Seattle, WA, USA) and bovine thrombin preparations purified by membrane filtration are claimed to be less immunogenic. Despite their reduced immunogenic nature, repeated administration of purified bovine thrombin preparations can result in the generation of antibovine thrombin antibodies. In this study, groups of rabbits were challenged repeatedly with bovine thrombin over a 6 months period and purified IgG preparations were obtained using protein G columns. In order to determine their cross reactivity with human recombinant thrombin (Recothrombin), two batches of this agent were evaluated by immunoblotting techniques using the rabbit IgG fractions. Recothrombin preparations cross reacted with the rabbit antibovine thrombin IgG. The cross reactivity of Recothrombin with antibodies was time dependent and a progressive increase in the immunoreactivity was evident. These results demonstrate that human recombinant thrombin can cross react with antibodies to bovine thrombin. Thus, the use of Recothrombin may not be recommended in patients previously treated/exposed to bovine thrombin.