Thrombin is a powerful topical hemostatic agent supplied as a freeze-dried, or lyophilized, powder that must be properly reconstituted before use. It acts by converting fibrinogen to fibrin at the bleeding site, leading to rapid clot formation. Improper mixing can lead to ineffective clotting, product waste, or, most critically, severe patient harm if the product is inadvertently administered intravascularly. Adherence to strict aseptic technique and manufacturer guidelines is non-negotiable for all medical professionals involved in preparation.
General Principles of Thrombin Reconstitution
While specific mixing instructions vary by manufacturer and product type, several core principles apply to all thrombin preparations:
- Aseptic Technique: All mixing must be performed under strict sterile conditions, typically within a sterile field in an operating room or clinical setting. Ensure all surfaces, components, and hands (if gloved) are kept sterile.
- Read the Instructions: Always consult the specific package insert and prescribing information for the product being used. Manufacturers like Pfizer and Baxter provide detailed, kit-specific instructions for products such as THROMBIN-JMI and FLOSEAL.
- Use the Correct Diluent: The standard diluent is sterile isotonic saline (0.9% sodium chloride). Other diluents may be specified for certain formulations, so verify before starting.
- Avoid Vigorous Shaking: Lyophilized proteins, including thrombin, can be denatured by vigorous shaking, which creates foam and can render the product less effective. Instead, use gentle swirling and inversion until the powder is fully dissolved.
- Correct Concentration: The volume of diluent added determines the final concentration of the thrombin solution. Different clinical applications require different concentrations. For example, plastic surgery may use a weaker 100 IU/mL concentration, while profuse bleeding requires a higher 1,000-2,000 IU/mL concentration.
- Immediate Use or Proper Storage: Reconstituted thrombin solutions have limited stability. They should be used promptly, but can often be refrigerated for a short period. Check the manufacturer's insert for specific storage and discard times.
Reconstituting Standard Thrombin Solution (e.g., THROMBIN-JMI)
For a basic topical thrombin solution, a vial of powder is reconstituted with sterile saline:
- Prepare the Vials: Flip the plastic caps off the vial containing the thrombin powder and the vial containing the sterile isotonic saline diluent.
- Attach Transfer Device (if supplied): If the kit includes a sterile transfer device, attach it according to the manufacturer’s instructions. This creates a closed system for sterile transfer between vials.
- Draw the Diluent: Using a sterile syringe (or via the transfer device), draw the required volume of sterile saline from its vial.
- Inject the Diluent: Slowly inject the diluent into the thrombin powder vial. A tip provided for the THROMBIN-JMI kit suggests placing the vial on a flat surface and injecting the diluent straight down.
- Dissolve the Powder: Gently swirl and invert the vial until the thrombin powder is completely dissolved. Avoid shaking.
- Withdraw the Solution: Draw the newly reconstituted thrombin solution back into the sterile syringe.
- Finalize: Label the syringe clearly with “FOR TOPICAL USE ONLY” and the concentration. The solution is now ready for application via syringe or for saturating a gelatin sponge.
Mixing for Flowable Gel Matrix (e.g., FLOSEAL or GEL-FLOW)
Mixing thrombin with an absorbable gelatin matrix creates a thick, flowable paste for hard-to-reach bleeding sites. The process often involves two syringes:
- Reconstitute Thrombin: Prepare the thrombin solution first, typically by injecting a diluent into the thrombin vial and drawing it back into a syringe.
- Connect Syringes: Remove the luer caps and connect the syringe containing the thrombin solution to the syringe containing the gelatin matrix.
- Mix Contents: Begin transferring the thrombin solution into the gelatin matrix syringe. Then, push the combined material back and forth between the two syringes. FLOSEAL instructions specify passing the mixture approximately 10 times until it is thoroughly mixed and homogenous.
- Wait and Recheck: After mixing, wait 10-15 seconds to allow the powder to fully hydrate and form a uniform gel consistency. The final mixture can be dispensed directly from one of the syringes.
Comparison of Thrombin Preparation Methods
| Feature | Standard Solution (e.g., THROMBIN-JMI) | Flowable Gel Matrix (e.g., FLOSEAL) |
|---|---|---|
| Form | Liquid solution | Flowable, gel-like paste |
| Purpose | Flooding or spraying bleeding surfaces; saturating sponges | Applying to difficult-to-reach or irregular surfaces |
| Components | Lyophilized powder and sterile saline diluent | Thrombin solution and pre-packaged gelatin matrix |
| Mixing Steps | Simple reconstitution in a single vial or syringe | Reconstitution of thrombin, followed by repeated syringe-to-syringe mixing with gel matrix |
| Consistency | Watery liquid | Viscous, putty-like gel |
| Duration of Use | Often shorter stability, e.g., 8-24 hours | Some kits stable for up to 8 hours after mixing |
Critical Safety Precautions
Proper mixing is essential, but safety extends to the entire handling process. Intravascular injection of thrombin is extremely dangerous and can cause fatal, extensive clotting. The following precautions must be observed:
- Never Inject: Thrombin is for topical use only. Always apply auxiliary labels that explicitly state “FOR TOPICAL USE ONLY - DO NOT INJECT” on the prepared syringe.
- Isolate and Differentiate: The Institute for Safe Medication Practices (ISMP) recommends segregating topical thrombin preparations from injectable medications to prevent accidental injection.
- Do Not Reuse: Discard unused contents and components after the specified time frame.
- Monitor for Hypersensitivity: Patients may develop antibodies to bovine thrombin, potentially leading to allergic reactions or severe bleeding/thrombosis. Monitor for symptoms like leg swelling, chest pain, or shortness of breath.
Conclusion
Mixing thrombin requires meticulous attention to detail, adherence to sterile protocols, and a clear understanding of the manufacturer’s instructions. Whether preparing a standard topical solution for saturating sponges or creating a specialized flowable gel for complex surgical sites, the fundamental principles of gentle reconstitution and accurate concentration remain paramount. The potential for fatal intravascular clotting necessitates unwavering commitment to safety measures, including clear labeling and physical separation from injectable medications. Always consult the official manufacturer's prescribing information to ensure the product is prepared and handled correctly for its intended clinical purpose. A well-mixed and safely administered thrombin solution is a vital tool for achieving reliable hemostasis during surgical procedures.
Optional outbound link: THROMBIN-JMI® Dosage and Administration - Pfizer Medical Information
