Serological analysis of patients treated with a new surgical hemostat containing bovine proteins and autologous plasma

Abstract

A randomized, controlled clinical study of the management of diffuse bleeding with CoStasis surgical hemostat, a new hemostat containing bovine thrombin and collagen with the patient's own plasma, included patients undergoing cardiac, hepatic, iliac, and general surgery. Sera from 92 patients treated with CoStasis and 84 control patients were collected preoperatively and at a post surgical follow-up of 8 weeks. Among the control group, 57 patients were treated with Instat collagen sponge in noncardiac indications. Results showed that antibody responses in the CoStasis clinical study were similar to the reported literature for all antigens screened and were not associated with any adverse reactions. The bovine thrombin preparations in CoStasis and other commercially available thrombins were compared with the use of SDS-PAGE and Western blot analyses. Within this clinical study, CoStasis was shown to be a safe and effective hemostatic product containing bovine thrombin and bovine collagen and no pooled human blood products.

Bovine Thrombin Safety Reporting: An Example of Study Design and Publication Bias

“…In 167 general, hepatic, cardiac, and orthopedic patients, CoStasis (Cohesion Technologies, Inc., Palo Alto, CA), a new formulation of thrombin and collagen composite, was compared with 151 similar surgical patients who received a control hemostat for hemistatic success and safety. Investigators found that CoStasis patients were more likely to demonstrate bovine thrombin antibodies than control hemostat exposed patients (48% positive or equivocal versus 19% P 0.01) [43,45]. Despite the fact that more than 80% of these patients had been exposed to thrombin in previous surgeries, only two ''nonserious adverse events occurred in one patient [which was] attributed to the use of Costasis'' [43,45].…”

“…Both edema and mild foreign body reaction ''resolved without incident'' [43,45]. The investigators observed that ''no adverse events or bleeding complications'' occurred in patients with high titers and that overall, ''no serious adverse events [were] related to the use of CoStasis'' [43,45].…”

“…Despite the fact that more than 80% of these patients had been exposed to thrombin in previous surgeries, only two ''nonserious adverse events occurred in one patient [which was] attributed to the use of Costasis'' [43,45]. Both edema and mild foreign body reaction ''resolved without incident'' [43,45]. The investigators observed that ''no adverse events or bleeding complications'' occurred in patients with high titers and that overall, ''no serious adverse events [were] related to the use of CoStasis'' [43,45].…”

“…Investigators found that CoStasis patients were more likely to demonstrate bovine thrombin antibodies than control hemostat exposed patients (48% positive or equivocal versus 19% P 0.01) [43,45]. Despite the fact that more than 80% of these patients had been exposed to thrombin in previous surgeries, only two ''nonserious adverse events occurred in one patient [which was] attributed to the use of Costasis'' [43,45]. Both edema and mild foreign body reaction ''resolved without incident'' [43,45].…”

Reduced Immunogenic Potential of Membrane Filtered Bovine Thrombin Preparations for Hemostatic Application

“…5 Although topical bovine thrombin preparations have been used successfully in most patients with isolated reports of serious adverse events, deranged hemostasis has developed in some surgical patients, resulting in severe or refractory bleeding and/or thrombosis. 8 It is thought that impurities in bovine thrombin preparations might be responsible for the adverse reactions. Patients exposed to topical thrombin preparations may develop antibodies to bovine thrombin, factor V/Va, and various other proteins found in these preparations.…”