Recombinant Film and Opportunity

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Potent Hemostatic Efficacy of a Novel Recombinant Fibrin Sealant Patch (KTF-374) in Rabbit Bleeding Models

One of the hallmarks of a good scientific study is that it not only answers a question about a process, but also raises questions that can inspire and focus future studies. Surgery has become very technology driven, and many surgical studies look at applications of technology. A good study demonstrates that one technique or tool is equivalent to or better than another that had previously been a standard in the surgical armamentarium. A very interesting study not only accomplishes that task, but the study reveals glimpses of the technology that generate a number of “what if” questions. Doors are opened to other potentials for the technology that may find applications or improvements that could change how surgeons provide care in a much broader area than the original study addressed.

The publication in this edition of the Journal by Sumika Miyabashira and co-workers on a fibrin sealant patch is a straightforward animal model comparison between two hemostatic adjuvants for intra-operative control of bleeding.¹ They used animal models of solid organ injury, venous and arterial bleeding. While there are numerous hemostatic adjuvants already approved and available for use in prehospital and operative settings^2,3. There are two subtle differences in the experimental product described in their study that are noteworthy.

The first is that the thin patch creates a transparent application. Figure 2A in their study depicts an application that adheres to folds and crevasses within the tissue and provides a clear view of the injury site. This means that the adjuvant does not need to be disturbed in order to re-inspect the surgical site. Areas that are at risk for continued bleeding are more likely to be identified without disturbing the sites that are adequately controlled. Any surgical tool that makes subsequent steps in the operative procedure easier and more likely to be successful has added value. Settings where a seal with these characteristics would save operative time could readily be suture line bleeding, biopsy site bleeding, and persistent bleeding from retroperitoneal dissection. While the hope would be that the described film would be helpful in explorations for traumatic bleeding as well as cut surfaces of solid organs, it is not clear that the current animal model provides the levels of injury that mimic these clinical settings. The animal models used in many prehospital studies of traumatic wounds and operative control of traumatic wounds are more severe that the rabbit model used by the authors on this preliminary study^2,4.

Second, the product is made of recombinant proteins (fibrinogen and thrombin) as the active agents. They are placed into separate layers that interact when the sheet becomes moistened. The research model implemented a heparin infusion to mimic a patient who is anti-coagulated for clinical reasons. The fibrin sealant sheet performed well compared to another accepted cellulose and fibrin product³. The technology to layer recombinant proteins into sheets that can be applied to wounds creates multiple “what if” scenarios that could impact many of the problem areas of surgical wounds. It might allow adding additional agents to help promote clotting in other clinical situations where specific clotting components are depleted or blocked⁵. The development process to create the study sheet with recombinant proteins suggests that a different sheet comprised of wound healing factors might also be created for use once bleeding is controlled. Improved healing of suture lines in patients with past radiation therapy, current chemotherapy or who are malnourished would be areas of investigation. The goal of the study was to demonstrate control over bleeding, but control over lymph and third space fluid leak is also a need that could be addressed. This initial study opens the door on numerous possibilities that may allow surgeons to both control bleeding and support tissue healing to minimize the traumatic impact of surgical procedures.

Significant amount of work is still needed before this technology can be approved for use in surgical applications. Studies need to be performed to determine the ideal layer thickness and components for different applications, as well as the initial tensile strength for the application. While in my opinion the transparent aspect of the film in situ is very valuable, it has not yet been shown that this characteristic can be retained while increasing the thickness, adding other active agents or inserting a layer to improve tensile strength if needed.

The durability of the clot produced by this patch needs to be established. If the patch reabsorbs too quickly re-bleeding could become an issue. In damage control surgery, irrigation during a second look procedure might disturb the hemostasis if the clot is not well adhered and the adhesive nature of the patch washes off. If the film retains its' integrity for a longer period, what other factors might be added to promote healing, reduce infection risks or other desired effects? A family of films might be created that can be layered at the time of surgery depending on surgical setting. The realm of operative procedures is large, and the clinical surgeon's needs vary with procedure and patient related variables. The interesting aspect of this deceptively simple study is that it opens doors to the flexibility to meet many of these needs in ways that we have not yet envisioned.

DECLARATION OF INTEREST

The author reports no conflicts of interest. The author alone is responsible for the content and writing of this commentary.