The effectiveness of the gelatin/thrombin combination to achieve hemostasis has been extensively studied and they have been found to be quite effective. = 43) had a numerically higher incidence of bleeding, thromboembolic events, hypersensitivity, and abnormal activated partial thromboplastin time (aPTT) as compared to those in the bThrombin group that did not develop antibodies (n = 157). This increase was not seen in those with anti-rThrombin antibodies (n = 3) as compared to those in the rThrombin group that did not develop antibodies (n = 198).38 The companion study for the Eslicarbazepine Acetate vascular subgroup in the previously mentioned phase 3 trial showed that adverse events were similar between the two thrombins in this subgroup. In patients undergoing vascular surgery, rThrombin demonstrated a superior immunogenicity profile versus bThrombin. Moreover, a significantly greater proportion of patients receiving rThrombin achieved hemostasis at 3 minutes compared with bThrombin (55% versus 39%, 0.05).39 Pooled results from a recently-published analysis Rabbit Polyclonal to DVL3 from 8 clinical Eslicarbazepine Acetate trials further show compelling evidence of the safety and the low immunogenicity of rThrombin. Data from 8 clinical trials, including the three mentioned above, were used to evaluate the safety and immunogenicity observations of rThrombin. Collectively, these trials included patients undergoing spinal procedures, major hepatic resections, creation of arterivenous grafts for hemodialysis access, peripheral arterial bypass procedures, and skin grafting for burn wounds. Adverse events and laboratory parameters were monitored until 29 days after the procedures. Immunogenicity was evaluated on plasma samples collected at baseline and on day 29. Of the 583 patients who were treated with rThrombin, 5 (0.9%) patients developed antibodies to rThrombin 29 days after surgery, and these antibodies did not Eslicarbazepine Acetate neutralize the biologic activity of native human thrombin (immunologic data only available for 552 patients). Adverse events reported for 10% of patients included incisional site pain, procedural pain, nausea, constipation, pyrexia, anemia, insomnia, vomiting, and pruritis. The reported adverse events were generally consistent with postprocedural events that are usually reported for patients undergoing surgery. Twelve (2.2%) patients with no previous exposure to rThrombin had pre-existing antibodies to rThrombin, however their antibody titers did not increase 10-fold at day 29. The collective results from this analysis demonstrate that rThrombin is well tolerated as a topical hemostatic agent in many surgical settings, and the data further contributes to the evidence of its safety and low immunogenic reactivity.40 Similar safety and immunogenic reactivity data seen in the above surgical patients were also seen in patients undergoing skin grafting for burns. This phase 2, multicenter, open-label study was of 72 patients with burn wounds who underwent partial or full-thickness autologous skin grafting. Patients received a spray application of rThrombin once every 5 minutes for up to 20 minutes. Of 62 patients for whom data was available, 1 patient (1.6%) developed anti-rThrombin antibodies at day 29. One other patient had pre-existing antibodies to rThrombin, however neither of these antibodies to rThrombin neutralized native human thrombin. Adverse events occurred in the majority of patients, however all were typical sequelae of skin grafting.41 One safety issue that has been raised is the question of whether rThrombin would be safe to use in patients who have received other forms of thrombin, such as bovine thrombin, in the past. There is a suggestion that the antibodies formed in those with prior exposure to bovine thrombin may cross-react with rThrombin.42 A recent phase 3b, open-label, single-group study addressed this issue by evaluating the immunogenicity and safety of rThrombin in 209 vascular and spinal operation patients at high risk for pre-existing antibovine thrombin antibodies, who received rThrombin as a topical hemostat. Immunogenicity data were collected at baseline and approximately 1 month after the operation. Of the 200 patients with complete immunogenicity data, 31 (15.5%) had pre-existing anti-bovine thrombin antibodies, and 4 (2%) had pre-existing anti-rThrombin antibodies. None of the 200 patients developed new antibodies against rThrombin on day 29 (defined as 10-fold increase in titer). The reported adverse events were.