How important is the immunogenicity issue (beyond a theorectical one)?
I also have a question for you. Do you test patients for bovine thrombin antibodies prior to surgical procedures?
The immunogenicity issues is not theoretical, it's just not well reported because there hasn't been anyone interested in funding the studies. Thrombin-JMI was grandfathered under FDA regulations, so it has never had prospective studies. The costs, both dollar and side effects, are not trivial if the patient on your table happens to have been treated with bovine thrombin before.
See publications from Duke's Dr. Jeffrey H Lawson, MD, PhD. He's one of the few docs that have been paying attention to this. See especially "Immunologic Impact and Clinical Outcomes After Surgical Exposure to Bovine Thrombin" Ortel et al., Annals of Surgery, 233(1), 88-96, January 2001. This article provides side effect analyses to show the impact of the immunogenicity issue. (Zymo didn't fund the study.) I reprint the available summary below. See the whole article for detailed information.
Objective
To determine prospectively the immunologic response and adverse clinical events in surgical patients exposed to bovine thrombin during cardiac surgical procedures.
Summary Background Data
Topical bovine thrombin is used extensively as a hemostatic agent during cardiovascular surgery. Antibodies developing after exposure to bovine thrombin have been anecdotally associated with hemorrhagic complications.
Methods
One hundred fifty-one patients undergoing cardiac surgical procedures were prospectively recruited for this study before surgical exposure with topical bovine thrombin. Immunoassays were used to determine antibody levels against both bovine and human coagulation proteins before and after exposure to bovine thrombin. Alterations in coagulation assay parameters and adverse clinical events were followed in all patients enrolled in the study.
Results
Baseline elevated antibody levels to one or more bovine coagulation proteins were observed most frequently in patients with a prior history of a surgical procedure during which bovine thrombin is frequently used. More than 95% of patients developed a seropositive response to bovine coagulation proteins, and 51% manifested elevated antibody levels to the corresponding human coagulation proteins after bovine thrombin exposure. Postoperative coagulation abnormalities were more common in patients with antibodies to human coagulation proteins. Patients with multiple elevated antibody levels to bovine proteins before surgery were more likely to sustain an adverse clinical outcome after surgery. Using a logistic regression model, the adjusted odds ratio for sustaining an adverse event with multiple elevated antibody levels to bovine proteins before surgery was 5.40.
Conclusions
Bovine thrombin preparations are highly immunogenic and appear to be associated with an increased risk for adverse clinical outcomes during subsequent surgical procedures. The clinical safety of these commonly used preparations needs to be reassessed, and reexposure to these agents should likely be avoided.
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