Antiphospholipid antibodies after surgical exposure to topical bovine thrombin.

ABSTRACT

Exposure to topical bovine thrombin during surgery frequently results in the development of antibodies to multiple protein and carbohydrate antigens. We investigated the frequency of increased levels of antibodies to cardiolipin and beta(2)-glycoprotein I (beta(2)-GPI) in two groups of patients, one exposed to bovine thrombin during cardiovascular surgery (n = 151) and a "control" group undergoing cardiovascular surgery but without exposure to bovine thrombin (n = 11). Anticardiolipin antibody levels were increased before surgery in 10 of the 151 patients exposed to topical thrombin (6.6%). Four to 8 weeks after surgery, 84 patients (55.6%) had increased anticardiolipin antibody levels (P <.0001). In the control group, an increased anticardiolipin antibody level was present in a single patient before and after surgery (9%). Increased levels of antibodies to bovine and human beta(2)-GPI were also observed after surgery in the patients exposed to topical thrombin (37.7% and 38.2%, respectively). Increased anticardiolipin levels correlated with higher levels of antibody to bovine, but not human, beta(2)-GPI. In addition, increased levels of anticardiolipin antibody were associated with higher levels of antibodies to bovine factor V and prothrombin, as well as human factor V. Antibody binding on an enzyme-linked immunosorbent assay conducted to detect anticardiolipin antibody was dependent on the presence of anionic phospholipid, indicating that binding was not linked to the fetal bovine serum in the blocking buffer alone. Seven of 8 patients with delayed thromboembolic complications had increased anticardiolipin IgG antibody levels after surgery, but this association was not statistically significant. Nevertheless, our findings support the recommendation that the clinical safety of these commonly used hemostatic agents should be reassessed.