Pharmacological properties of the drug Tachocomb
Absorbent hemostatic agent for local use. The drug consists of a collagen plate coated on one side with fibrin glue components (highly concentrated fibrinogen and thrombin), which promote blood clotting. The adhesive surface of the plate is marked in yellow (riboflavin). Upon contact with a bleeding wound, the blood clotting factors contained in the coating (fibrinogen, thrombin) are released, and thrombin activates the conversion of fibrinogen to fibrin. The plate adheres to the wound surface due to the polymerization reaction; During this process (plate 3–5 min), the collagen forms a water- and air-tight layer. During this process, the plate must be pressed against the wound surface. In the body, the components of the plate undergo enzymatic breakdown within 3–6 hours. A special production process guarantees maximum safety against viruses and bacteria entering the contents of the plate.
One of the main goals of any surgical intervention is to minimize blood loss in order to avoid postoperative complications and the need for blood transfusions. Considering that blood transfusions themselves carry the risk of complications, the importance of searching for new surgical approaches to hemostasis and expanding the arsenal of tools used in this becomes obvious. This problem has become especially acute in the practice of laparoscopic surgical interventions, when the hands of the operating surgeon are not able to directly contact the tissues. As is known, during laparoscopic operations it can be difficult to achieve reliable hemostasis in the gallbladder bed. When suturing hollow organs during endoscopic operations, there is also often a need for additional sealing of the suture line. The urgent need for reliable means of local hemostasis, which could be freely used in laparoscopic surgery, prompted the development of new hemostasis systems.
Until recently, both in open surgical interventions and in laparoscopic hemostasis was achieved by ligation, suturing or coagulation of the vessel. Local hemostatic agents are extremely useful adjuncts to surgical hemostasis. The introduction of new techniques, including local ones, has made it possible to significantly facilitate the work of surgeons during laparoscopic surgical interventions.
A hemostatic drug must have the required properties: clinical safety, an optimal ratio of economic costs and benefits. Many auxiliary means introduced into the practice of laparoscopic interventions have found wide application in open surgery. Some of them are widely used and available in all operating rooms [1]. The most common laparoscopic staplers are Ultratision and Ligasure. Mechanical techniques such as suturing, trimming, and electrocoagulation have been used for many years and are the mainstay of surgical hemostasis today. The Ultracision stapler is a unique hemostasis tool that uses ultrasound to generate local energy that promotes adequate hemostasis. It is used when working on small and medium-sized vessels with a diameter not exceeding 7 mm. The Ligasure stapler is also a very useful tool that we use widely in our practice. Compared to the earlier version (Ultracision), it allows hemostasis of larger vessels. An endoscopic stapler is another equally effective tool for hemostasis on large vessels during laparoscopic operations.
Biological hemostatic methods were first developed in the 1940s and continue to be improved. These products have proven themselves in laparoscopic surgery. Local hemostats and sealants serve to achieve adequate hemostasis, help increase tissue strength, strengthen and seal the suture line when traditional methods (mechanical, thermal and chemical) are ineffective or impossible.
Such agents are classified as local hemostatics, sealants and adhesives. Hemostatics promote blood thickening and fibrin clot formation. Sealants create sealing barriers. Adhesives help bind tissues together. Biological hemostats are made from animal, human, plant or synthetic material.
The latter are represented by drugs: Beriplast, Quixil, Tachosil (Tachocomb), Tisseel, Tissucol and medical products: Floseal, Syvek, Tabotamp, Curaspon, Coseal, Glubran, Dermabond, Histoacryl. The mechanism of action differs between drugs and medical devices. The first, consisting of human thrombin, factor XIII, fibrinogen, fibronectin and tranexamic acid, reproduce the last phase of coagulation, when fibrinogen under the influence of thrombin is transformed into fibrin monomer, which polymerizes into a fibrin clot under the influence of factor XIII. The latter creates a mechanical barrier during bleeding [2].
Medical products consist of a base - collagen and bovine thrombin, cellulose polymers soldered in the form of a sponge, polymers from oxidized reduced cellulose, gelatin. These include synthetic polyethylene glycols and cyanoacrylates, which act on a mechanical principle and are collectively called “fibrin glues”.
The clinical literature describes cases of the use of fibrin glues to create a strong network (weave), effective for closing fistulas, as well as for the prevention of postoperative adhesions.
Fibrin glue is a sealant consisting of fibrinogen concentrate and thrombin suspension. Thrombin solution is presented in two categories: commercial product and laboratory-developed. Beriplast, Bioglue, Tissucol, Tisseel, etc. are most commonly consumed as commercial products [3]. Currently, to achieve hemostasis, we also actively use gelatin sponges, which are a mixture of proteins derived from collagen. We most often use Spongostan or Surgiform. Upon contact with bleeding tissues, gelatin granules swell, turning into a dense mass, and stop bleeding, blocking the path of blood flow [4].
Oxidized cellulose is isolated from cotton and is presented in the form of plates. In addition to its mechanical effect, cellulosic acid facilitates hemostasis by denaturing blood proteins. The most commonly used product from this group is Surgicel.
Purified animal collagen, which has been used since 1970, stimulates local platelet release and provides mechanical interaction to promote clotting. The product is obtained from bovine collagen, so it contains small doses of bovine whey protein, which must be taken into account, since a number of patients have allergic reactions to such products.
Collagen is presented in the form of sponges or syringes. Most commonly used hemostatic collagens are presented in the form of preparations: Floseal, Syvek, Tabotamp, etc. Preparations Beriplast, Quixil, Tisseel, Tissucol, etc. are more often used for gluing tissues, strengthening and stabilizing sutures. Some of the products include components such as sodium, silicon, aluminum, magnesium oxide, which adsorb water from the blood, promoting the concentration of coagulation factors, accelerating natural hemostasis.
In some cases, for external bleeding, the drug Celox is used, a highly effective hemostatic agent based on Chitosan, a natural highly purified polymer. The mechanism of action of this drug is the binding of positively charged Celox granules to negatively charged red blood cells and the formation of a gel-like clot. However, Celox does not interfere with the normal blood clotting process and is not a chemical agent. The value of the drug lies in the fact that it is effective in stopping blood containing anticoagulants (Warfarin, Heparin) and antiplatelet agents. However, after 24 hours of being in the wound, Celox begins to break down under the action of lysozyme to the natural metabolite glucosamine, the latter is easily excreted from the body. As we can see, this method is also not without its drawbacks and is not suitable for use in laparoscopic surgery.
So, local hemostatic agents and sealants have become important tools in modern surgery, thanks to them the number of complications associated with bleeding is significantly reduced.
Of course, most topical absorbent hemostatic products, such as fibrin sealants, are not very effective for massive bleeding because they do not have sufficient adhesive strength to resist blood flow. The idea of creating optimal hemostatic agents is aimed at reducing the use of blood products in planned and emergency surgery and increasing the ability to control any type of bleeding, both arterial, venous and parenchymal. Such materials must have sufficient adhesive force so that the plug they form is a reliable and strong obstacle to the flow of blood.
The use of new hemostatic materials in laparoscopic surgery is exciting. In this article we want to discuss the experience of using the Austrian drug Tachocomb as a local hemostatic agent during laparoscopic surgical interventions.
The drug Tachocomb is a collagen sponge in the form of a plate, with active components applied to one of the surfaces: human thrombin and fibrinogen (Fig. 1).
Rice. 1. Structure of the Tachocomb plate.
Tachocomb contains collagen isolated from horse tendons, lyophilized human fibrinogen, thrombin and riboflavin, which colors the adhesive surface yellow.
The drug is available in a ready-to-use form. It is sterile and intended for immediate use.
Tachocomb contains fibrinogen and thrombin in the form of a dry coating (collagen sponge surface). Upon contact with physiological fluids (blood, lymph or electrolyte solutions), the components covering the sponge dissolve and partially diffuse onto the wound surface. This is accompanied by a fibrinogen and thrombin reaction, initiating the last phase of physiological blood clotting.
Fibrinogen is converted into fibrin monomer, which then polymerizes to form a fibrin clot (thrombus), which tightly holds the sponge collagen on the surface of the wound. With the help of blood coagulation factor XIII, fibrin polymers are cross-linked to form a solid, mechanically strong mesh structure with good adhesive properties, which ensures reliable closure of the wound. Collagen additionally stimulates platelet aggregation, thereby enhancing the hemostatic effect.
The polymerization reaction in the adhesive layer occurs within 3-5 minutes, after which the drug plate is tightly connected to the tissues and becomes impermeable to liquids and air. During the polymerization process, the plate must be pressed tightly against the wound surface.
In the body, the components of the drug undergo progressive biodegradation. The fibrin clot is metabolized in the same way as endogenous fibrin, undergoing fibrinolysis and phagocytosis. Sponge collagen also undergoes similar degradation by resorptive granulation tissue.
The most well-known indications for the use of the drug Tachocomb in laparoscopic surgical interventions are to stop bleeding during operations on parenchymal organs or in case of accidental damage to the latter. The technique for applying Tachocomb to splenic wounds depends on the depth of damage to the parenchyma. In this case, it is also necessary to take into account the location of the damage. In cases of organ decapsulation on any surface, it is enough to apply a plate of the drug and fix it tightly [5]. In case of ruptures of the spleen along the diaphragmatic surface, it is necessary to pinch the vascular pedicle with your fingers before application and hold it for the entire period of fixation in order to avoid blood leakage from under the edge of the preparation, which will significantly disrupt its hemostatic properties. Hemostasis of central ruptures of the spleen should not be carried out using the drug Tachocomb, since in this case there is a high risk of secondary bleeding. In this situation, splenectomy is performed [6].
With the help of the drug Tachocomb, it is also possible to stop bleeding from giant gastric ulcers, with pinpoint damage to large arterial and venous vessels, to seal a vascular suture, to stop bleeding near nerve trunks (when the use of electrocoagulation is unacceptable), to strengthen and stabilize intestinal sutures and anastomoses in prognostic unfavorable situations (for example, peritonitis).
During resections of the liver or pancreas, in addition to providing a hemostatic effect, Tachocomb allows one to prevent the leakage of bile and pancreatic juice. However, large bile ducts and the duct of Wirsung must be ligated before application [7]. On the liver wound, the drug is applied in one layer [8], on the pancreatic stump, due to the aggressiveness of pancreatic juice, in two layers, with the drug directly protruding onto the intact surface by 2 cm.
It should be remembered that the possibilities of Tachocomb are not limitless.
. Using this drug without additional means, it is impossible to achieve hemostasis from large arteries and veins in case of terminal wounds. If parenchymal bleeding is combined with bleeding from a large main vessel, the latter should first be ligated, and then the hemostatic properties of the drug should be used. It is also impossible to ensure stable hemostasis using Tachocomb when strengthening technically incorrectly applied surgical sutures, to close intestinal fistulas, etc. [9].
Fixation of the drug on the bleeding surface is carried out for 3-5 minutes, which is quite enough to achieve hemostasis. During pressing, the plate must not be moved, as this prevents the formation of a blood clot and reduces the hemostatic effect.
In some cases, with heavy bleeding, leakage of blood from under the edge of the preparation may indicate insufficient hemostasis in some part of the wound surface. In this case, you should carefully place a new plate on top of the previous one, also fixing the preparation for 3-5 minutes. As a rule, this technique allows to achieve final hemostasis.
The literature describes cases of stopping bleeding from giant gastric ulcers when they are unresectable. As is known, in severe patients with a history of massive bleeding, with severe concomitant pathology, and with disorders of the blood coagulation system, radical surgery is dangerous and not always tolerated. In these situations, after gastrotomy, the bleeding main vessel is locally sutured, and then Tachocomb is applied to the entire surface of the ulcer. The drug plate must exactly match the contours of the ulcer and not extend onto the mucous membrane. It is believed that with such an application, not only a hemostatic effect is achieved, but also faster healing of the ulcer in the postoperative period as a result of the stimulating effect of the Tachocomb drug on the underlying surface. This method can also be used as a palliative control of bleeding in unresectable gastric tumors, supplemented by ligation of the gastric or gastroepiploic arteries of the appropriate localization.
As for stopping bleeding when large vessels are damaged, I would also like to point out the successful experience of using this drug. It is known that during surgery, especially during lymph node dissection, there may be cases of separation of small arterial or venous branches from the great vessels or their puncture wounds. In such cases, hemostasis can be achieved by applying Tachocomb without resorting to a surgical suture. To do this, you should temporarily, for approximately 3 minutes, stop the blood flow through the vessel by clamping the latter and apply a plate of the drug with a length of at least 3 cm along the axis of the vessel. This type of bleeding control can be achieved with both traditional and laparoscopic surgery. In the same way, you can seal the vascular suture by placing the drug on the vessel in the form of a coupling (wrapping technique).
It is known that under unfavorable conditions (peritonitis, intestinal obstruction), the risk of failure of sutures and anastomoses increases. As a number of clinical studies show, the use of the plastic properties of the Tachocomb drug can significantly reduce the risk of complications, which is achieved by increasing the mechanical strength of the anastomotic area and reducing the microbial contamination of this area. Among other things, it has been proven that the drug helps stimulate the fibroblastic reaction and angiogenesis processes. The last factor is the most important, as it helps prevent insolvency, reduces the severity of inflammation, and accelerates reparative processes.
To strengthen surgical sutures, Tachocomb is applied in one layer, the plate is positioned along the entire suture line, with the edges of the preparation on the serous tissue by at least 2 cm. In this case, before application, it is necessary to moisten the preparation with sterile saline solution at the rate of 100 µl per 1 cm2 area or a solution of an antibacterial drug, which is supposed to be used parenterally in the postoperative period. Temporary fixation for 5 minutes is carried out with a gauze swab soaked in the same solution. After fixation, the tampon must be removed carefully, holding the corresponding edge of the Tachocomb plate. Do not move an incorrectly applied medication. In this case, a second one is placed on top of the first plate, also completely covering the suture line.
It was found that in order to strengthen the suture line in the projection of anastomoses applied using end-to-end or end-to-side methods, it is necessary to cover the entire suture line with a plate, capturing part of the intestinal mesentery by at least 2 cm. In the case of lateral anastomoses, not only the anterior and posterior anastomoses are strengthened lip of the anastomosis, but also a sutured stump of the afferent loop [10].
The application of the drug should be performed last before suturing the wounds of the anterior abdominal wall, in order to avoid the risk of displacement of the plate during the insertion of a nasointestinal tube or sanitation of the abdominal cavity.
Considering all of the above, it seems obvious that the drug plays a major role in laparoscopic operations, since these interventions do not have sufficient opportunities to achieve adequate hemostasis in a number of bleedings, the danger of coagulation near the main bile ducts or large vessels increases, and difficulties arise in tightening nodes when comparing infiltrated tissues . In these cases, the hemostatic and plastic properties of Tachocomb are irreplaceable.
In our practice, during laparoscopic operations of various types, we widely use the drug Tachocomb both as a local hemostatic agent and as a sealant to stabilize and strengthen the suture line on hollow organs, especially when forming colorectal anastomoses. We present the results of our observations.
To place the drug into the abdominal cavity, it is given a semicircular shape, and it is necessary to place it with the adhesive surface inward, and in this form it is placed in the adapter. The adapter is inserted into the working port and then the Tachocomb plate is pushed into the abdominal cavity, where it is picked up by a clamp and placed on the wound surface. The application of the drug is made with two endoclamps, then it is fixed - pressed with a small pad over the entire surface of the plate. You can also use nearby organs for fixation. To do this, you can press the hepatic angle of the colon with a tuffer to the plate located in the projection of the gallbladder bed, or use the gallbladder to fix the plate located in the projection of the sutures on the duodenum after suturing the perforated ulcer. The edge of the liver can be used to fix the plate in the projection of the common bile duct sutures after its suturing [11].
The twisted form of the Tachocomb drug that has appeared significantly facilitates the introduction of the drug into the cavity during laparoscopic interventions (Fig. 2).
Rice. 2. Twisted form of the drug Tachocomb.
After removing the twisted form of Tachocomb from the inner sterile packaging, the drug can be passed into the cavity through a 10 mm trocar using forceps. In the abdominal cavity, a twisted sponge is applied with the yellow side to the wound surface at the site of bleeding and untwisted using instruments. After unfolding, the sponge must be pressed with a damp cloth and held in place for 3-5 minutes (Fig. 3).
Rice. 3. Technique for application of the twisted form of the drug Tachocomb. If necessary, the sponge can be moistened with 0.9% sodium chloride solution.
The literature also describes cases of closing small, no more than 0.7 cm, perforated gastroduodenal ulcers with a Tachocomb plate without suturing them. The indication for this method of closing an ulcerative defect was a certain location of the perforation hole, since, for example, suturing a defect in the area of the pylorus can lead to deformation of the latter and stenosis. The presence of pronounced perifocal inflammation contributes to an increased risk of suture cutting, which also speaks in favor of the use of the drug Tachocomb.
In this case, we applied the drug in two layers to form a more durable patch. A plate of such size was used that it extended beyond the edges of the perforation hole by 1.5-2.0 cm. Then, after 5 minutes required for gluing the drug to the serous cover, a second plate of the drug of a larger size was applied on top of the first, first the surface of the first plate moistened with saline solution. The tightness was controlled by introducing a small amount of air through a nasogastric tube [12].
We have also used the drug Tachocomb during laparoscopic operations in patients with adhesive disease. Due to the frequent occurrence of capillary bleeding from the intestinal wall after separation of adhesions, we also had to resort to the application of the drug Tachocomb, since with such bleeding it is not possible to use an endoloop or electrocoagulation.
In conclusion, we note that our experience with the use of Tachocomb during laparoscopic operations has shown it to be a good local hemostatic agent. During laparoscopic operations, the use of the drug Tachocomb in some cases allows one to avoid switching to an open method of surgery in case of unsuccessful electrocoagulation of the gallbladder bed. The drug is indispensable in cases where hemostasis cannot be achieved using electrocoagulation. One of the new directions in the use of the drug Tachocomb was its application to the suture lines of hollow organs in order to strengthen their mechanical strength and additional sealing. All these properties of the Tachocomb drug in the future may expand the indications for the use of laparoscopic operations for various diseases of the abdominal organs.
The authors declare no conflict of interest.
Indications for use of the drug Tachocomb
Used for hemostasis and tissue adhesion, especially during surgical interventions on parenchymal organs, for example, liver, spleen, pancreas, kidneys, adrenal glands, lungs, thyroid gland, lymph nodes; in cases where it is impossible to stop bleeding using conventional methods or when the effectiveness of such methods is insufficient; for therapeutic purposes for lymphatic, biliary and liquor fistulas; for stopping bleeding in ENT surgery, gynecology, urology, vascular and bone surgery, traumatology, etc.
Tachocomb, 2 pcs., sponge
In rare cases, patients who have previously used fibrin sponges/hemostatic products may experience hypersensitivity or allergic reactions, which may include angioedema, burning and tingling sensations at the application site, bronchospasm, chills, skin redness, urticaria (including generalized forms), headache, hypotension, lethargy, nausea, anxiety, tachycardia, chest tightness, tingling sensation, vomiting, wheezing.
In isolated cases, these reactions can progress to severe anaphylactic shock. Such reactions may primarily occur with repeated use of the drug or when used in patients with known hypersensitivity to the components of the drug.
Immunogenicity:
The appearance of antibodies to components of fibrin sponges/hemostatic products is rare.
At the same time, in a clinical study of Tachocomb® in liver surgery, which studied the formation of antibodies in patients, 26% of 96 patients receiving Tachocomb® showed the appearance of antibodies to collagen from equine tendons. Antibodies to horse tendon collagen, which develop in some patients after taking Tachocomb®, did not react with human collagen. One patient developed antibodies to human fibrinogen.
There were no adverse events associated with the formation of antibodies to human fibrinogen or equine tendon collagen. Clinical data regarding repeated exposure to Tachocomb® are extremely limited. No immune-mediated adverse events were reported during repeated dosing of the drug in two patients during the clinical study; at the same time, their status for antibodies to collagen or fibrinogen is unknown.
If such symptoms develop, use of Tachocomb® should be discontinued immediately.
Classification of adverse reactions (ADR) by frequency: very common (≥1/10); often (≥1/100, <1/10); not often (≥1/1000, <1/100); rare (≥1/10,000, <1/1,000); very rare (1/10,000, including individual reports); frequency unknown (cannot be estimated from available data).
Immune system disorders
Frequency unknown: anaphylactic shock, hypersensitivity.
Vascular disorders
Frequency unknown: thrombosis.
Gastrointestinal disorders:
Frequency unknown: obstructive intestinal obstruction (during operations on the abdominal organs), ileus (during operations on the abdominal organs).
General disorders and disorders at the site of application:
Frequency unknown: spikes.
Use of the drug Tachocomb
Used under sterile conditions. Before use, the wound surface must be cleaned of blood, disinfectants and other liquids. It is recommended that surgical gloves and instruments be kept free of blood and body fluids to avoid adhesion to the plate. The plate is applied to the wound surface with the side that contains blood clotting factors (marked in yellow) and pressed for 3–5 minutes. For wounds with exudation, the drug can be used without additional moisturizing. For wounds without exudation, before use, it is recommended to moisten the plate with a physiological solution to achieve complete connection with the dry areas of the wound surface. The moistened plate should be applied immediately!
Tachocomb®
For topical use only. Do not use intravascularly.
Mode of application
Tachocomb® is in sterile packaging and ready for use. The drug can only be used from undamaged packaging. After opening the package, re-sterilization of Tachocomb® is not possible. The outer aluminum packaging bag can be opened in a non-sterile operating room area. The inner sterile blister should be opened in a sterile area. Tachocomb® must be used immediately after opening the sterile inner packaging. Tachocomb® should be applied to surgical wound surfaces under sterile conditions.
Before applying the sponge, the wound surface must be cleaned of blood, disinfectants and other liquids.
After removing the Tachocomb® flat sponge from the inner sterile packaging, the sponge should be moistened with 0.9% sodium chloride solution and used immediately. The side coated with active substances and marked in yellow is applied to the wound surface, if necessary, additionally moistened with 0.9% sodium chloride solution and pressed lightly for 3-5 minutes. Pressing is carried out with moistened gloves or a moistened pad.
After removing the rolled Tachocomb® sponge from the inner sterile packaging, it should be applied immediately through the trocar without prior moistening. When unwinding, the sponge is applied with the yellow side covered with active substances onto the wound surface using tweezers, if necessary, additionally moistened with a 0.9% sodium chloride solution and lightly pressed with a damp cloth for 3-5 minutes. This creates conditions for improving the adhesion of Tachocomb® to the wound surface.
The Tachocomb® sponge may adhere to blood-stained gloves or instruments, or adjacent tissue. This can be avoided by cleaning surgical instruments, gloves and surrounding tissues.
Insufficient cleansing of adjacent tissues can lead to the development of adhesions.
Once you have finished pressing the Tachocomb® sponge onto the wound, carefully remove the glove or pad. To prevent the sponge from leaving the surface, it can be held in place at one end, for example with a pair of tweezers.
In case of severe bleeding, Tachocomb® can be used without prior moisturizing.
The sponge is applied to the wound surface and pressed lightly for 3-5 minutes.
During neurosurgical procedures, Tachocomb® should be applied over the primary dural closure.
The twisted Tachocomb® sponge can be used in both open and minimally invasive procedures and can be passed through a port or trocar with a diameter of 10 mm or larger.
Dosing
The size and number of Tachocomb® sponges depend on the size of the wound surface.
The edges of the wound should be covered with a sponge by 1-2 cm. If more than one sponge is required to close the wound surface, then when applied to the wound their edges should overlap each other.
The sponge can be cut to the desired size.
In clinical studies, individual dosages were typically 1 to 3 sponges (9.5 cm x 4.8 cm); Up to 10 sponges have been reported. For smaller wounds, such as minimally invasive procedures, it is recommended to use smaller sponges (4.8 cm x 4.8 cm or 3.0 cm x 2.5 cm) or rolled sponges (based on the 4.8 cm x 4 sponge .8 cm). Unused sponges or their fragments must be destroyed.
