Evaluation of a Novel Fibrin Sealant Patch in Hemorrhage Control After Vascular or Hepatic Injury.

INTRODUCTION: Acute hemorrhage remains the leading cause of death in potentially survivable injuries. The use of topical hemostatic agents has increased over the last two decades with the evolution of damage control surgery. By 2008, the military widely adopted Combat Gauze as the hemostatic dressing of choice for compressible hemorrhage. The goal of this study was to compare the performance of a novel fibrin sealant patch to Combat Gauze in two clinically relevant models of hemorrhage. MATERIALS AND METHODS: Yorkshire swine underwent unilateral femoral artery puncture or a grade V liver laceration with timed free bleeding then received either the fibrin patch or Combat Gauze packing with 3 minutes of standardized pressure. Animals were then resuscitated to maintain a mean arterial pressure of 60 mmHg for 4 hours. Hemostasis, blood loss, resuscitation volume, survival, vessel patency, and hematologic parameters were evaluated. RESULTS: Hemostasis was equivalent in both groups after hepatic and vascular injury. Survival was 80% in the fibrin patch vascular injury group and 100% in all other groups. Hematologic parameters were not significantly different between treatment groups. Femoral artery patency was 80% in both groups after vascular injury. With simulated ambulation after vessel injury, 60% of the Combat Gauze group and 80% of the fibrin patch group remained hemostatic (p > 0.05). In simulated re-exploration with packing removal, all animals rebled after hemostatic product removal. CONCLUSION: There was no significant difference in hemostasis between a novel fibrin patch and Combat Gauze after extremity arterial or hepatic injury. This novel fibrin patch may have a clinical advantage over the Combat Gauze, as it can be left in the body, thereby limiting the potential need for reoperation.

The influence of pterygium morphology on fibrin glue conjunctival autografting pterygium surgery.

To evaluate the influence of pterygium morphology on the efficacy and safety of fibrin glue in pterygium surgery with conjunctival autografting. A prospective case series. During a period of 15 months, 45 patients (51 eyes) were recruited from the General Hospital for pterygium surgery. Seven eyes (13.73 %) were operated on for a recurrent pterygium. Autologous conjunctiva was harvested from the superior bulbar conjunctiva and fixed with fibrin glue. The pterygia were preoperatively divided into atrophic/grade 1 (n = 18; 35.29 %), intermediate/grade 2 (n = 22; 43.14 %) or fleshy/grade 3 (n = 11; 21.57 %) according to clinical morphology. Patients were evaluated for intraoperative and postoperative complications and recurrence rates. The success rate was defined by no pterygium recurrences. Patients with 2-year follow-ups were included in this study. Fifty-one patients (21 females/30 males) with a mean age of 60-65 years (range 24-87 years) took part in the study. All patients completed the study. No intraoperative complications were noted. Postsurgical complications included graft edema (n = 4; 7.8 %), graft hyperemia (n = 2; 3.8 %), and graft dislocation (n = 3; 5.9 %); these complications were transient. One graft unfastened completely (2 %) and five pterygium recurrences occurred (n = 5; 9.8 %). The overall success rate was 90 % after 2 years. In grade I group there were no recurrences, in grade 2 group there were two recurrences, and in grade 3 group there were three recurrences. There were significantly more recurrences in grade 3 group than in grade 2 group. There were more recurrences in both groups than in group 1 (60 vs 40 vs 0 % of all recurrences, p ≤ 0.05). The use of fibrin glue is a safe, easy and effective technique for attaching the conjunctival autograft in pterygium surgery. The morphology of pterygium influences recurrence rates, without significance for intraoperative and postoperative complications.

Transporous hernia mesh fixation with fibrin sealant in an in vitro model of spray application.

BACKGROUND: The spray application of fibrin sealant (FS) is widely used for atraumatic mesh fixation in open and laparoscopic hernia surgery. Studies focusing on the optimization of sealant distribution are rare. This study elucidates the impact of spray distance and pressure, the thrombin concentration of the FS, as well as the mesh design on the spray process and the resulting sealant distribution. Furthermore, the effect of interrupting the spray process on sealant distribution was investigated. MATERIAL AND METHODS: Three different meshes were sprayed in a vertical test arrangement with 0.4 mL FS. Fibrin sealants containing 4 and 500 IU/mL thrombin (Tisseel and Artiss; Vienna, Austria) provided by Baxter Biosciences were used. The application distances varied from 5 to 8 cm. The relative fibrin sealant distribution on the individual mesh surfaces was evaluated and compared, as well as loss of FS and patterns of clot formation. RESULTS: Spray distances between 5 and 8 cm led to a homogenous sealant distribution. Lower thrombin concentrations led to significant losses of FS due to slower polymerization. Differences of the fibrin sealant distribution and mesh pore sizes were found. No differences between continuous and discontinuous application were observed. CONCLUSION: The spray application of FS provides a uniform sealant film in a defined range of distances. However, design and pore size of different meshes substantially impact sealant distribution. These findings should be considered when selecting prosthesis for hernia repair. In general, the amount of sealant should not exceed 0.08 mL per cm(2) to avoid obstruction of mesh pores.

Fixation of mesh to the peritoneum using a fibrin glue: investigations with a biomechanical model and an experimental laparoscopic porcine model.

BACKGROUND: In recent years, the use of fibrin glue has become an established practice in several areas of surgical treatment. For example, fibrin glue is used increasingly as an alternative method for mesh fixation in hernia surgery, significantly helping to reduce the incidence of chronic pain. The experiments in this study were aimed at elucidating the extent to which tack- or suture-based permanent fixation can be replaced by fixation with fibrin glue for laparoscopic intraperitoneal repair of abdominal wall hernias. METHODS: In an initial series of experiments conducted with a biomechanical model, the strength of the fibrin glue for fixation of lightweight mesh (TiMesh light) to muscle tissue was compared with its strength of fixation to the peritoneum. In a second series of experiments, mesh was laparoscopically implanted in an established porcine model. Fibrin glue was used for mesh fixation in six animals. Laparoscopic exploration and explantation of the meshes were conducted after 4 months. Planimetric analysis was performed to investigate adhesion and shrinkage of the mesh surface. RESULTS: The strength of fibrin glue for fixation of mesh to the peritoneum was significantly less than for its fixation to muscle tissue (11.86 N vs. 47.88 N; p = 0.001). Three of the implanted meshes were not completely integrated, and two of these were dislocated. On the average, adhesions were seen on 16% of the mesh surfaces. The mesh shrinkage rate was 24.2%. CONCLUSION: Mesh fixation alone to the undamaged peritoneum in the intraperitoneal region cannot be recommended because of the risk for dislocation. Additional fixation using sutures, tacks, or both is needed until the mesh material is completely integrated.

Hemodinamic behavior of arterial anastomosis using fibrin sealant: experimental study in swine.

OBJECTIVES: To evaluate the flow, tear pressure, the need of reinforcement stitches in sutured arteries reinforced or not using fibrin sealant after a cross-section. METHOD: Tissucol fibrin sealant was used. The femoral and carotid arteries of seventeen swine from the same breed (weighing from 15 to 20 kg) were cross-sectioned after heparinization and subjected to anastomoses using a single continuous plane of prolene 7-0. We worked with 68 artery samples, 34 in the Treatment Group and 34 in the Control Group. For each animal, one carotid and one femoral artery randomly received fibrin sealant with the contralateral side being used as a control. The need and the number of reinforcement stitches were recorded. Ten minutes after protamine infusion, the animals were sacrificed and the arteries were catheterized. The arteries were measured and placed on a flow meter. The arteries were then subjected to air infusion at increasingly higher pressures (stepwise increases of 25 mmHg), the grafts were dipped in saline solution, the first air leakage was observed and the tear pressure recorded. RESULTS: The external diameters and thickness of the arteries were similar in both the Treatment and Control Group. There was no significant difference between the groups regarding the tear pressure (p=0.329), flow rate (p=0.943) and the number of samples with a tear pressure above 200 mmHg. However, the sealant reduced the number of reinforcement stitches necessary (p=0.029). CONCLUSION: Fibrin sealant reduces the need of additional stitches.

Commercial fibrin sealants are not equivalent in a rabbit liver-resection model which quantitatively evaluates hemostasis and formation of adhesions.

A rabbit partial liver resection model was used to determine the hemostatic effectiveness of a new fibrin sealant. Persistent bleeding, with a mean bleeding time of 372 s and blood loss of 18 ml, from a resected lobe of the liver was achieved after rabbits in the untreated control group had been infused continuously with unfractionated heparin over 20 min with 0.2 IU/ml at a rate of 1 ml/min. Spraying the resected surface with the new fibrin sealant, Quixil, reduced bleeding to < 1 ml and the post-resection bleeding times was 25 s. Bleeding time, blood loss and the volume of sealant used in the rabbit model were inversely correlated with the thrombin concentration in the sealant. In direct comparisons with Tissucol and Beriplast, Quixil was associated with the shortest bleeding times, the lowest volume of sealant used and the lowest score of abdominal adhesions.

[Autologous fibrin sealant preparing system in coronary artery bypass grafting].

Autologous fibrin sealant (AFS) which is not based on the conventional method of co-administering fibrinogen, thrombin and aprotinin was prepared by Vivostat system, and was used in coronary artery bypass grafting (CABG). The purpose of this study was to investigate the safety and efficacy of the AFS prepared by the Vivostat system. In 6 of 68 cases of CABG, normal AFS was not prepared due to device failures. AFS was prepared and sprayed in 62 cases. There were the total of 230 anastomosis sprayed AFS and the bleeding could not seen in 225 anastomosis. Surgical hemostatic procedures (4 cases) were or other sealant usage (1 case) was performed 5 bleeding anastomosis sites. The rate of hemostasis at the anastomosis using AFS was 97.8%. This study was conducted in patients undergoing CABG. In this group of patients, a number of commercial available fibrin sealant products are routinely used. The usefulness of Vivostat as medical device to prepare and administer AFS was confirmed in this study.

Database review of possible factors influencing point-of-care platelet gel manufacture.

The application of autologous platelet gel (APG) to surgical wounds has been advocated during the last 10 years to speed bone and wound healing, minimize infection, and modify postoperative pain. There are few data available to confirm these claims. Prior to organized study, consistency and agreement in manufacture of the APG is needed. In this study, an attempt is made to isolate factors that are important in developing a consistent gel. A database review was performed to determine factors that affect PG quality and function. Quality was assessed by platelet count and fibrinogen concentration, whereas function was assessed by an arbitrary scale of gelling, in which a "1" was equal to a soup texture, "3" equal to a "Jell-O" consistency, whereas a grade of "2" was somewhere in between. Data specific to the blood draw and platelet-rich plasma sequestration were collected. Two hundred and sixty cases of APG production were reviewed. The volume of blood drawn was dependent on the machine used. Gelling of the APG was independent of platelet count and fibrinogen concentration. Gels that were rated soupy had an average platelet count of 540 K/microL+/-327 K/microL and a fibrinogen concentration of 225 mg/dL+/-76 mg/dL whereas a firm gel had an average platelet count of 486 K/microL+/-264 K/microL and a fibrinogen concentration of 229 mg/dL+/-78 mg/dL. The manner in which the blood was drawn along with the site from which the blood was drawn influenced the platelet concentration of the platelet-rich plasma. Optimal platelet counts were obtained when blood was drawn from a peripheral vein and sequestration was performed with the Medtronic Sequestra or the Medtronic Magellan. Ultimate gelling of PG is independent of fibrinogen and platelet concentrations. This work suggests a need for further research into the manufacture of APG.

The use of human fibrin glue in the surgical operations.

Human Fibrin Glue (HFG) is made of two components contained in separate vials: a freeze dried concentrate of clotting proteins, mainly fibrinogen, Factor XIII and fibronectin (the sealant) and freeze dried thrombin (the catalyst). The first component is reconstituted with an aprotinin solution that inhibits tissue fibrinolysis. The second component (thrombin), available in 500 I.U. concentration, is dissolved with calcium chloride. It is so a set of substances involved in the hemostatic process and in the wound healing, conferring to the product the following important properties: hemostatic and sealing action, through the strengthening of the last step of the physiological coagulation; biostimulation, which favors the formation of new tissue matrix. The indications for the use of human fibrin sealant are numerous and present in all the surgical branches. A randomized controlled trial of 50 patients undergoing hernia repair according to Lichtenstein's technique under local anesthesia was performed. Patients had concurrent coagulopathies as a consequence of liver disease or long-term treatment with anticoagulants for ischemic heart disease or cardiac rhythm disturbances. Coagulopathies were defined according to the following criteria: prothrombin time < 10.5 seconds, activated partial thromboplastin time < 21 seconds, and fibrinogen < 230 mg/dL. Patients were randomized in a 1:1 ratio with (group A) or without (control group B) use of human fibrin glue: Postoperative hemorrhagic complications were significantly reduced in group A (4%) compared with group B (24%). This study showed that human fibrin glue is effective in preventing local hemorrhagic complications after inguinal hernia repair in patients with concurrent coagulation disorders.

Addition of a propyl gallate-based procoagulant to a fibrin bandage improves hemostatic performance in a swine arterial bleeding model.

Fibrin bandages manufactured by Nycomed Austria (TC-S) were modified by the addition of Hemostyptin (HS), a proprietary platelet-activating reagent containing propyl gallate. HS was added as an additional layer to TC-S fibrin bandages and the bandages were tested for hemostatic efficacy in a swine femoral artery bleeding model. Injuries were treated with a TC-S+HS bandage preparation using HS lyophilized onto a bandage surface that was then attached to the fibrin dressing. This preparation qualitatively and quantitatively exhibited more robust blood clotting at the surgical site than the control bandages. TC-S+HS bandages were more effective than control bandages with a difference in blood loss of 251.8+/-66.5 g for TC-S bandage alone, n=12 vs. 121+/-40.7 g, n=13 for the TC-S+HS bandage, P=0.05. Bleeding times were shortened for animals treated with the HS fortified bandages and residual platelets counts in these animals were higher.

Epsilon-amino caproic acid additive decreases fibrin bandage performance in a swine arterial bleeding model.

epsilon -Amino caproic acid (EACA), a lysine analog that inhibits the activity of plasmin, was added to Nycomed (TC-S) fibrin bandages, and the bandages were tested for hemostatic efficacy in a swine femoral artery bleeding model. The blood loss using the bandage with EACA (TC-S+EACA; 728.8+/-132 g, n=5) was much greater as compared to the TC-S bandage alone (TC-S; 237.8+/-47.9 g, n=6, p=.02). The time to "cessation of bleeding" (T(b)) was also increased for animals treated with TC-S+EACA bandages compared to the TC-S controls (33.6+/-10.8 min vs. 9.2+/-2.2 min; p=.05). Although plasma fibrinogen concentration decreased in animals treated with the TC-S+EACA bandage, activated partial thromboplastin times (aPTT) and thrombin times (TT) were decreased. Animals treated with the TC-S control bandage exhibited no changes in fibrinogen, aPTT or TT. Prothrombin times (PT) were unchanged in either group. In conclusion, addition of EACA to the Nycomed product decreased fibrin bandage efficiency.

[Effectiveness of fibrin tissue adhesive for colocolic anastomosis reliability]. / Kolokolik anastomoz güvenliginde fibrin doku yapistiricinin etkinligi.

Leakage from a colonic anastomosis remains a major complication of surgery for colon emergencies and is associated with a significant increase in postoperative hospital stay and mortality rate. The purpose of our study was to investigate whether fibrin sealant, a well known tissue adhesive, will augment healing of bowel anastomosis in an experimental peritonitis model. Forty-eight male Sprague-Dawley rats were randomized into four groups. All rats underwent conventional sutured colo-colic anastomosis. The rats in group 3 and 4 had been exposed peritonitis before that procedure. In groups 2 and 4 fibrin sealant was added to the suture line. The measurements of bursting pressure and histopathological evaluations of suture lines revealed that peritonitis was deleterious to healing of colonic anastomosis. It was also seen that fibrin sealant augments healing of colonic anastomosis both in normal and peritonitis models.

Thromboelastograph assay for measuring the mechanical strength of fibrin sealant clots.

In order to provide sustained hemostasis or tissue sealing, fibrin sealants must generate adhesive clots with mechanical properties capable of resisting forces, such as shear, that might break or tear the clot. Commercial preparations of fibrin sealants should generate clots of adequate and consistent mechanical strength. The mechanical strength of fibrin sealants is often measured as bonding strength in in vivo or ex vivo animal wound models. These tests can be useful predictors of clinical efficacy. However, these, as well as many in vitro tensile strength tests for fibrin sealant, tend to be laboratory specific and require extensive reagent preparation time and analyst training. The thromboelastograph has historically been used to screen for plasma protein and platelet disorders that lead to defective clot formation. The authors have developed a simple in vitro test, using a standard thromboelastograph that can provide reliable, reproducible information on the rheology of clots generated by fibrin sealant preparations. Using this method, the shear strength of fibrin sealant clots was measured and shown to correlate with the fibrinogen, but not the thrombin, concentration in the sealant. Shear strength was also shown to correlate with the sealant concentration of the fibrin cross-linking proenzyme, factor XIII. Sealants containing lysine, which can act as an alternate substrate for factor XIII enzyme and prevent efficient fibrin chain cross-linking, were shown by this method to generate clots of substantially reduced shear strength. The method distinguished between thrombin-catalyzed clot formation and other fibrinogen clotting mechanisms as evidenced by the significantly lower shear strength associated with batroxobin-generated fibrin clots.

[Production and clinical application of fibrin sealant with high concentrated fibrin (fibrin patch)].

OBJECT: The sealing properties of fibrin sealant with high concentrated fibrin (fibrin patch) were examined. MATERIAL AND METHODS: A commercial fibrin sealant (Bolheal) produced from pooled human plasma was utilized for this study. The fibrin sealant made of fibrinogen and thrombin solutions mixed in a volume ratio 5:1 was applied as the fibrin sealant with high concentrated fibrin (fibrin patch). The burst pressure of the fibrin clots of either 1:1 or 5:1 mixing ratio, which sealed the small holes, was measured by a water-leak preventing model. The tensile strength of the fibrin patch was measured by the breaking pressure of the fibrin clot. The burst pressure of the fibrin patch, which sealed the dural defect with a diameter of 15 mm, was compared with that of expanded polytetrafluoroethylene (ePTFE). RESULTS: The burst pressure was elevated from 287 +/- 23.1 to 445 +/- 30.5 mmHg by changing the mixing ratio from 1:1 to 5:1. The breaking pressure of the fibrin patch showed 131 +/- 25.4 mmHg and that of the patch mixed at the ratio of 1:1 showed 46.6 +/- 9.9 mmHg. The result of dural repair with the fibrin patch revealed higher sealing effectiveness than that of ePTFE. The burst pressure averaged 70.5 +/- 21.4 mmHg in the fibrin patch samples and 51.4 +/- 13 mmHg in the ePTFE samples. CONCLUSION: The fibrin patch revealed higher performance as a sealant and has the potential to be a candidate for acceptance as the new dural repair material.

Purification of salmon clotting factors and their use as tissue sealants.

Fibrin sealant prepared from the blood of farmed Atlantic salmon (Salmo salar) represents a potential source of well-controlled natural material with utility in a variety of clinical settings. A potential advantage of this material is a lower probability of viral or bacterial infection that has limited general approval of fibrin glues made from human or bovine proteins. This report describes the purification of fibrinogen from salmon blood, the use of fibrin glues derived from this material to promote wound healing in rats, and the antigenic response to this material. While the low ambient temperature of these cold water fish significantly lessens the probability of infectious transmission to humans, fibrinogen and factor XIII derived from S. salar are activated by human thrombin at 25 degrees C and 37 degrees C to form clots equivalent to those formed by human fibrin. We compare the reactivity of salmon and human fibrinogen with human and bovine thrombin and the structure and viscoelastic properties of the resulting fibrin gels over a range of pH and salt concentrations. The efficacy of salmon fibrin glues in a wound healing assay and the low antigenic response to salmon fibrinogen suggest that this material may substitute for proteins derived from mammalian sources with lower probability of infections.

Fibrin sealant: summary of a conference on characteristics and clinical uses.

The 2-day conference clearly outlined the formulations of products that are being developed or are commercially available in Europe. The major difference between products in the United States and those in Europe is that US manufacturers are preparing fibrin sealant that does not contain aprotinin, epsilon amino caproic acid, or any other type of antifibrinolytic agent, whereas antifibrinolytic agents are included in all such preparations used in Europe. The conference provided no clear consensus that such agents are essential to the efficacy of the product. Although many investigators believe in the clinical benefit of fibrin sealant, most of the studies to demonstrate efficacy have not been performed in a well-controlled fashion. However, fibrin sealant, if found in a controlled trial to have clinical efficacy, could be approved by the FDA for a narrow indication. Opportunities remain for greater exploration of different forms of the product, not only as a hemostatic agent, but as an adjunct to wound healing and as a matrix for delivery of drugs and proteins with other biologic activities.

Evaluation of tissue adhesives in closure of scleral tunnel incisions.

Using a biomechanical wound strength model, we compared the efficacy of cyanoacrylate and fibrin glues used to close scleral tunnel incisions. Scleral tunnel incisions were made in four groups of rabbits: (1) traditional self-sealing incision, (2) modified non-self-sealing incision, (3) method 2, closed with cyanoacrylate glue, or (4) method 2, closed with fibrin glue. Overall, Groups 1 and 4 showed the least clinical reaction, the slightest decrease in intraocular pressure (which recovered to baseline by day 7), and the most significant recovery of postoperative astigmatism. Initially, the bursting pressure in Groups 1 and 3 was statistically the highest (P < .005). By day 3, wound strengths in Groups 1 and 4 were comparable. Bursting pressure decreased in Groups 2 and 3 by day 7. Our results indicate that clinical responses, intraocular pressure, induced astigmatism, and ultimately wound strength were comparable in fibrin-glue-closed scleral pocket and sutureless self-sealing cataract incisions. Although cyanoacrylate glue cures immediately and initially demonstrates a strong adhesive quality, it causes a severe inflammatory response that inhibits subsequent collagen remodeling. Fibrin tissue adhesives may have an application as adjunctive means of closing scleral tunnel incisions.

Evaluation of canine-derived fibrin sealant as a hemostatic agent.

The purpose of this study was to determine whether canine-derived fibrinogen concentrate applied with bovine thrombin was a safe and effective topical hemostatic agent. A canine liver biopsy model was selected to test this product. Cryoprecipitate was prepared from frozen canine plasma using two freeze/thaw/centrifugation cycles. Six healthy adult dogs (weighing more than 18 kg) were used in the fibrin sealant study, and an additional three dogs were used as controls for the liver biopsy. A 1 x 3 cm liver biopsy specimen was obtained, digital pressure was applied to reduce bleeding, and the fibrinogen concentrate was immediately sprayed on the bleeding surface simultaneously with bovine thrombin (1,000 IU/mL). The mean +/- standard error of the mean (SEM) blood pressure at time of biopsy was 98 +/- 9 mm Hg, and the rate of hemorrhage from the cut liver edge was 8.0 +/- 1.1 mL/min. The total blood loss during fibrin sealant application was 37 +/- 9 mL and total time for hemostasis was 5.5 +/- 1.3 minutes. There was no additional hemorrhage after application of the fibrin sealant. In the three control dogs, fibrin sealant was not applied and only digital compression was used to decrease hemorrhage. Before digital compression, the rate of hemorrhage from the cut liver edge was 13.1 +/- 3.1 mL/min. Bleeding had not stopped after 10 minutes of compression and the mean postcompression rate of hemorrhage was 4.0 +/- 2.6 mL/min. Signs of secondary bleeding after fibrin sealant was applied were not evident during the immediate postoperative period or over the next 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)