According to the American College of Obstetricians and Gynecologists (ACOG) committee opinion published in 2020 on topical hemostatic agents, limited data existed evaluating the use of topical hemostatic agents in gynecologic and obstetric surgery. Thus, recommendations are primarily based on findings extrapolated from studies on the use of these agents in other types of surgeries. Topical hemostatic agents have been frequently used when the use of electrocautery or sutures for hemostatic control of surgical bleeding is considered unsafe or not ideal, including bleeding in areas with nearby vulnerable structures (e.g., ureters or nerves) or in the presence of diffuse bleeding from peritoneal surfaces or cut surfaces of solid organs. On the other hand, the panel discouraged using topical hemostatic agents for routine prophylaxis of postoperative bleeding due to an increased risk of infection, adhesion formation, and other complications. [1]
To select the most appropriate and cost-effective topical agent, clinicians should be familiar with the distinct mechanisms of action, potential adverse effect profiles, and varying costs associated with an individual agent. Generally, physical agents (oxidized regenerated cellulose, microfibrillar collagen, and gelatin matrix) are more likely to be effective in patients without coagulation abnormalities and in less severe bleeding situations. However, when bleeding is more active or in the presence of coagulopathy, biologically active agents such as topical thrombin (human, bovine, recombinant, or thrombin+gelatin granules) and fibrin sealants may be considered. While limited head-to-head study (Table 1) has suggested similar efficacy between bovine thrombine (e.g., Thrombin-JMI) vs. recombinant thrombin (e.g., Recothrom), surgeons should avoid administering bovine-derived thrombin in patients who have previously been exposed to the agent due to increased risk of severe antibody-mediated reactions upon re-exposure. On the other hand, use of recombinant thrombin product should be avoided in patients sensitive to snake or hamster proteins. [1]
A 2009 review evaluated available literature regarding safety and efficacy of topical thrombins, including Thrombin-JMI and Recothrom. Bovine thrombin (e.g., Thrombin JMI) is produced by extracting prothrombin from bovine plasma, while human recombinant thrombin (e.g., Recothrom) is produced using recombinant DNA technically from genetically modified Chinese hamster ovary cells that produce human thrombin precursors. Human recombinant thrombin is identical to naturally occurring human thrombin in regards to amino-acid sequence. Topical bovine thrombin has been associated with hemostatic abnormalities due to formation of antibodies against bovine thrombin and/or factor V, which may cross-react with human factor V, sometimes resulting in factor V deficiency and potentially excessive bleeding. This likelihood increases with repeated applications; paradoxical reactions are also possible. The true incidence of such events has not been accurately determined, as most data are derived from case reports. Conversely, human plasma-derived thrombin avoids cross-immunogenicity risk, but it may carry a risk of transmitting infection from infected plasma donors. Human recombinant thrombin is plasma-free, minimizing risk of both immunogenic cross-reactivity and infection transmission from human plasma donors. [2], [3], [4]
A limited number of trials have evaluated therapeutic efficacy of these products, with even fewer investigating direct, comparative efficacy. A phase 3 noninferiority study conducted by Chapman et al. (Table 1) compared the efficacy and tolerability of human recombinant vs. bovine thrombin in 401 adults undergoing hepatic resection, spinal surgery, peripheral arterial bypass surgery, or arteriovenous graft formation, finding similar outcomes. Another study by Weaver et al. (Table 2) compared human recombinant and bovine thrombin in 144 vascular surgery patients, finding improved hemostasis with human recombinant thrombin. Notably, no placebo arm was incorporated into either of these trials. Despite its long history of use, no published studies were identified evaluating the efficacy of stand-alone topical bovine thrombin compared to placebo. [2], [3], [4]
All thrombin products contain a contraindication for injection into the circulatory system due to risk of thrombosis. Bovine thrombin should not be administered to patients with hypersensitivity to any component or other components of bovine origin. Human recombinant thrombin should not be used in patients with known hypersensitivity to hamster proteins, snake proteins (enzymes derived from snake venom are used in this product to activate precursors to human thrombin), or any component of human recombinant thrombin. Based on 2008 data, the average wholesale price of human recombinant thrombin was slightly more expensive than bovine plasma-derived thrombin (approximately $103-$434 vs. $88-$340, depending on formulation). Both bovine thrombin and human recombinant thrombin are supplied as sterile powders to be stored at room temperature, as opposed to human plasma-derived thrombin, which is supplied as a frozen sterile solution and must be stored under refrigeration. Reconstituted bovine thrombin can be refrigerated for up to 24 hours or stored at room temperature for up to 8 hours prior to use. Reconstituted human recombinant thrombin can be stored at room temperature for up to 24 hours prior to use. [2], [3], [4]