Topical thrombin is a potent hemostatic agent that plays a vital role in the surgical setting, acting locally to control minor bleeding and oozing from capillaries and small venules. To serve a variety of surgical applications, it is produced in several different drug forms. The choice of formulation depends on the type of bleeding, the accessibility of the site, and the surgeon's preference. The main forms include powder for reconstitution, prefabricated solutions, and combinations with other absorbent materials.
Lyophilized Powder for Reconstitution
The most common and versatile form of topical thrombin is a sterile, freeze-dried powder, or lyophilized powder, that requires reconstitution with a sterile diluent, typically isotonic saline, before use. This form offers several advantages, such as extended shelf life and stability. For example, THROMBIN-JMI is supplied as a powder, often in vials alongside a separate vial of diluent.
Once reconstituted, the thrombin solution can be applied in several ways:
- Sprayed on: A pump spray or syringe spray kit can deliver the solution as a fine mist to cover broad, oozing surfaces.
- Flooded directly: A syringe and small-gauge needle can be used to flood a specific bleeding area.
- Saturated sponge: Absorbable gelatin sponges can be immersed in the solution and then applied to the bleeding site.
Handling Precautions: It is crucial to use aseptic techniques during reconstitution. The label on reconstituted thrombin products is prominently marked with a warning: FOR TOPICAL USE ONLY – DO NOT INJECT. Inadvertent injection can cause fatal thrombosis.
Prefabricated Solutions and Fibrin Sealants
Some formulations of topical thrombin are available as pre-prepared liquids, such as frozen solutions or as part of more complex products like fibrin sealants. These formulations are designed for specific uses where quick and precise application is needed.
- Frozen Solutions: Brands like EVITHROM contain human-derived thrombin supplied as a frozen solution in vials. This eliminates the need for on-the-spot reconstitution but requires specific cold storage and thawing procedures.
- Fibrin Sealants: These products combine topical thrombin with fibrinogen to create a powerful adhesive that mimics the final stage of the body's natural clotting cascade. Fibrin sealants come in various formats:
- Liquid Kits: Some are supplied as two separate liquid components that are mixed upon application to form a clot, functioning as a surgical glue.
- Patches: Other products, such as TachoSil, are pre-made patches or sponges impregnated with human fibrinogen and thrombin. The patch is applied directly to the bleeding tissue, where the components are released to form a stable, localized fibrin clot.
Combinations with Absorbable Materials
Topical thrombin is also integrated with absorbable materials to create flowable hemostatic agents. These are particularly useful for controlling bleeding in hard-to-reach or irregularly shaped areas.
- Absorbable Gelatin Matrix: Products like GEL-FLOW NT involve mixing the reconstituted thrombin solution with an absorbable gelatin powder to create a thick, flowable paste or gel. This mixture can be smeared or pressed against the bleeding surface.
- Collagen Combinations: While less common for modern thrombin, historical methods sometimes combined thrombin with collagen-based materials for hemostasis.
The Source of Thrombin
The source of thrombin used in manufacturing is an important consideration, impacting potential immunogenicity and allergic reactions.
- Bovine Thrombin: Derived from bovine (cow) plasma, this was one of the earliest topical thrombin products developed. However, it carries a risk of immunologic complications, where patients can develop antibodies against bovine proteins that may interfere with human coagulation factors.
- Human Thrombin: Prepared from pooled human plasma, this variant (e.g., EVITHROM) reduces the risk of bovine-related immune reactions but carries a theoretical risk of transmitting infectious agents, though modern manufacturing includes stringent viral inactivation and removal processes.
- Recombinant Thrombin: This is a man-made protein (e.g., RECOTHROM) produced via recombinant DNA technology in a Chinese Hamster Ovary (CHO) cell line. It is structurally similar to native human thrombin but eliminates the risk of transmitting human or bovine pathogens.
Comparison of Topical Thrombin Forms
| Feature | Powder for Solution (e.g., THROMBIN-JMI) | Prefabricated Solution (e.g., EVITHROM) | Fibrin Sealant (e.g., TachoSil) | Flowable Gel Matrix (e.g., GEL-FLOW NT) | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Drug Form | Sterile lyophilized powder + diluent | Frozen liquid solution | Pre-coated patch or two-liquid kit | Powder + diluent + gelatin matrix | ||||||
| Preparation | Requires reconstitution before use | Thawing required before use | Ready to use (patch) or mix components | Reconstitution and mixing required | n | Primary Use Case | Broad range of surgical bleeding; versatile application | Oozing from capillaries and small venules | Diffuse bleeding over large areas; sealing | Controlling bleeding in hard-to-reach, irregular spaces |
| Application Method | Spray, flood, or saturated sponge | Flooding, syringe application, or saturated sponge | Direct application of the patch | Smeared or pressed via syringe applicator | ||||||
| Storage | Room temperature (powder); refrigerated (solution) | Frozen storage required | Room temperature or refrigeration | Room temperature (components) | ||||||
| Pros | Long shelf life, versatile, multiple applications | Faster preparation time vs. powder | Immediate, localized effect; simple application | Effective in difficult anatomical locations | ||||||
| Cons | Requires mixing; risk of contamination during prep | Specific storage requirements; potential for viral transmission (human-derived) | Higher cost; specific applications only | Requires careful mixing; potential for tissue reaction to gel |
Conclusion
Topical thrombin is not confined to a single drug form but is manufactured and supplied in diverse formats to address a wide range of surgical needs. From the traditional lyophilized powder that offers versatility and a long shelf life, to ready-to-use frozen solutions, and advanced fibrin sealants or flowable gels, each formulation provides a distinct set of benefits for managing surgical bleeding. The evolution from bovine-derived products to safer human and recombinant forms further highlights the ongoing advancements in pharmacology. Surgeons and healthcare professionals must select the appropriate drug form, considering the type of procedure, bleeding characteristics, and potential patient sensitivities, while always adhering to the critical instruction of topical-only application to ensure patient safety.
