Fibrin glue versus autologous platelet-rich fibrin - comparison of effectiveness on the cohort of patients with fistula-in-ano undergoing video-assisted anal fistula treatment : Journal of Minimal Access Surgery

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Fibrin glue versus autologous platelet-rich fibrin - comparison of effectiveness on the cohort of patients with fistula-in-ano undergoing video-assisted anal fistula treatment

Ramachandran, Riju1,; Gunasekharan, Vaishnavi1; Pillai, Anoop Vasudevan1; Raja, Suyambu1; Nair, Anjaly S2

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Journal of Minimal Access Surgery 18(3):p 443-449, Jul–Sep 2022. | DOI: 10.4103/jmas.jmas_297_21
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Meinero introduced video-assisted anal fistula treatment (VAAFT) as a minimally invasive, sphincter preserving procedure for the management of fistula-in-ano in 2011. The procedure routinely involves the identification and fulguration of the entire length of the tract. This is followed by the instillation of Fibrin glue into the tract, to reinforce the closure of the tract.[1] However, fibrin glue used in this procedure costs between 7000 and 11000 INR for 1 ml depending on the manufacturer.

Our department has been using autologous platelet-rich fibrin (PRF) in the healing of complex wounds with excellent results. As an extension, we attempted the use of PRF instead of fibrin glue in patients undergoing VAAFT with encouraging results.

However, there is no literature comparing these two adjuncts for VAAFT. Since we had satisfactory results with both the adjuncts, we decided to compare the two materials as adjuncts with VAAFT in the treatment of fistula-in-ano.

The aim of this study was to compare the efficacy of fibrin glue versus PRF as adjuncts for VAAFT.


This is a single institution retrospective observational study on a cohort of patients (n = 65) who underwent VAAFT at a tertiary care centre from 2015 to 2020. Ethical committee clearance was taken for the study vide IRB-AIMS-2020–361 before starting the study. Details of the patients were collected from the hospital database.

VAAFT is performed only by one surgical unit at the institute since 2012. All patients were operated on by a single senior surgeon. Patients operated upon in the first 3 years during the learning curve were not considered for the study due to bias in the study results.

All the patients had been initially evaluated in the outpatient with a clinical history and examination. Once the diagnosis of fistula-in-ano was made, important characteristics of the fistula were evaluated with magnetic resonance fistulogram. All the patients were evaluated for surgical fitness. The procedure was performed under spinal anesthesia. Patients were routinely placed in the lithotomy position during the procedure. Occasional patients with external opening that were ergonomically difficult to access in lithotomy positions were placed in the jackknife position. The operative process for VAAFT was tract identification, mapping, endoscopic fulguration of the internal lining of the entire length tract, and closure of the internal opening. The process of fistula mapping was similar in all patients. The entire tract was then fulgurated using a flexible monopolar electrode (Karl Storz, Tuttlingen, Germany). The internal opening was closed using a figure of eight technique and then advancing the mucosa over this using 2-0 vicryl sutures (Ethicon®, U. S LLC). The treated length of the fistula tract was filled with fibrin glue or PRF. Fibrin glue was used in the initial years of the study and PRF in the later years.

Fibrin glue is routinely recommended for use as an adjunct to standard surgical techniques both as a haemostatic and as a sealant to prevent leakage from colonic anastomoses.[23] This adjunct (Tisseel®, Baxter/Evicel®, Omrix Biopharmaceuticals) was prepared according to the manufacturer's recommendation and injected into the tract Figure 1.

Figure 1:
(a) Syringe, (b) Human Fibrin component, (c) Human thrombin component, (d) loading the vials on the syringe, (e) Both the components loaded into syringe and ready for injection, (f) R - Glue being pushed into the treated tract sing a special catheter

Patients who were to receive PRF as an adjunct were shifted to the blood bank on the morning of surgery. Around 150 ml of blood was withdrawn into sterile conical tubes and immediately centrifuged at a rate of 3000 rpm for 10 min. The blood was then allowed to settle for one to 3 h, following which the yellow, clear jelly-like PRF was obtained. This was used to pack the tract after endoscopic fulguration Figure 2.

Figure 2:
(a and b) Paltelet rich fibrin, the bottom half is the platelet free area and the yellow jelly like material if the PRF. A buff layer in between the two layers contain a lot of healing factors. (c) PRF being pushed into the treated cavity. (d) PRF completely pushed inside the cavity. (e) Treated tract after PRF insertion

All patients were discharged on post-operative day 1 and reviewed after 3 weeks, 3 months and 6 months and the details were documented in the case files.

As a part of this study, after ethical clearance in July 2020, all patients were either reviewed in the outpatient department or telephonically interviewed to record any recurrence after the 6 months follow-up (range of 6 months to 5 years) to complete the process of data collection. Any new discharge in the treated fistula, the appearance of new openings or other related symptoms like perianal pain or bleeding were recorded. Adverse events if any were also recorded. A telephonic interview was conducted for the patients that could not travel back or were unwilling to come back to our institution for review [Appendix 1].

In this series of patients undergoing the VAAFT procedure, those who received fibrin glue as an adjunct were included in Group A and those who received PRF were included in Group B. The procedure was considered a failure if the patient had no decrease in discharge and the wound had not healed within 3 months. The fistula was considered to have healed if the external opening had closed and there was no pain or discharge from the region for more than 3 months. Recurrence was considered when the patient had reappearance of symptoms after the fistula had healed, within 1 year of surgery.

The initial five patients from each of the 2 groups were selected as a pilot for calculating the sample size. Based on the recurrence rates in these ten patients, with a confidence interval of 95% and a power of 80%, our sample size comes to 44 (22 in each arm)

Data of all patients in both groups were analysed in relation to demographic details, type of fistula, number of fistulous tracts, the relation of the fistula to levator ani, time taken to heal, recurrence and failure of the procedure.

Statistical analysis was performed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, Newyork, USA). Categorical variables were expressed using frequency and percentage. Continuous variables were expressed using mean, Standard Deviation, median and interquartile range. To test the statistical significance of the difference in the proportion of categorical variables between two groups, Chi-square test was used. To test the statistical significance of the difference in the meantime of healing between two groups, Mann–Whitney U-test was used and for age, Student's t-test was used. P < 0.05 was statistically significant.


The study included 65 patients who underwent VAAFT over 5 years in our department. Follow-up period in these patients ranged from 6 months to a maximum of 5 years.

In this cohort, Group A had 41 patients who received fibrin glue as adjunct and Group B had 24 patients who received PRF as an adjunct. In Group A, 25 had complete healing, 13 had recurrence and 3 had failure of the procedure. In Group B, 22 had complete healing and 2 had recurrence. Parameters such as age, sex and time for healing were comparable in the two groups [Table 1].

Table 1:
Demographic data

When the two groups were compared for recurrence (%), we found a significant reduction in the recurrence, where PRF was used as an adjunct (P = 0.032) [Table 2].

Table 2:
Recurrence (%) between the two groups

There was also a significant reduction in recurrence in those patients who had a single internal opening (P = 0.045), single external opening (P = 0.03) and complex tracts (P = 0.033) in Group B [Table 3].

Table 3:
Comparison of recurrence (%) with respect to fistula parameters between the two groups

There were three patients with Crohn's disease in Group A. All three patients had failure of the procedure. In these patients, the fistula healed when PRF was used as an adjunct to VAAFT. There was no statistical difference for fistula healing in Group B when the relation of the fistula to the number of tracts, relation to the anal sphincter and to levator ani were considered specifically. There were no major complications in both groups of patients in our series.

On comparing the patients having recurrent fistula-in-ano treated by VAAFT we found a significantly increased healing rates in those that received PRF as adjunct [Table 4].

Table 4:
Results in patients with recurrent fistula


Fistula-in-ano, an abnormal communication between the rectum or anal canal and the perianal skin, is a sequeale of cryptoglandular sepsis.[4] Parks et al., classified fistula-in-ano as intersphincteric, transsphincteric, suprasphincteric and extrasphincteric.[5] They based this classification on the relationship with the sphincters. Conventional surgical techniques for the management of fistula-in-ano, including fistulectomy, fistulotomy and seton placement, have been associated with high morbidity, risk of recurrence and faecal incontinence.[6]

Meinero and Mori introduced VAAFT as a minimally invasive alternative to the conventional surgical methods, without the complications of the latter. The procedure involved the application of fibrin sealant to reinforce the closure of the internal opening.[1]

Fibrin was introduced in the year 1909 as a biological adhesive.[7] Fibrinogen, thrombin, and calcium ions-the constituents of fibrin glue result in clot formation when combined and stimulate healing. Abel and Hjortrup published the first case series in the early 90s pertaining to the use of fibrin glue in the treatment of anal fistula with a healing rate of 60% (in ten patients) and 52% (in 15 patients), respectively.[89] More recent studies have reported a healing rate of 21%–69% following the use of fibrin glue as an upfront/adjunct modality for the treatment of fistula in ano.[10] In our department, we had been using Fibrin glue as an adjunct to VAAFT with a 60% success rate.[11]

Various adjuncts have been tried to fill and close the remnant tract after procedures like VAAFT and ligation of intersphincteric fistula tract (LIFT) with relatively good results. Fibrin glue and Permacol collagen paste (Medtronic®) are good examples of these adjuncts.[12]

PRF has been used in our department for the management of complex wounds and for diabetic as well as venous ulcers with satisfactory results.[13] It has not been used for healing of the fistula. Autologous PRF was described by Choukroun et al. in 2006 and from then on has been used in various disciplines of surgery and dentistry.[1415] Growth factors, cytokines and proteins found in autologous PRF hastens wound healing as well as reduce the risk of infections.[1617] This principle was applied to VAAFT, and PRF was tried as an adjunct to VAAFT instead of fibrin glue.[18] In the cohort, PRF was used more frequently in patients undergoing VAAFT after 2018, whereas patients who underwent VAAFT between 2015 and 2018 had received only Fibrin glue. An actual randomisation could not be done as Fibrin glue was the only adjunct described in the literature for VAAFT during the period from 2011 to 2017.

The presenting complaint of these patients was discharge of pus, blood or fecal matter from the external opening soiling the dressings and pain in the perianal area. Most patients had a decrease in the discharge immediately following surgery and the wound healed by 6–8 weeks. Persistence of discharge more than 3 months was considered as a failure of the procedure. A second sitting of the procedure was considered for this set of patients.

One of our patients with recurrent fistula-in-ano in a background of Crohn's disease had undergone multiple open fistulectomy procedures and two sittings of VAAFT with fibrin glue as an adjunct. Following this, VAAFT with PRF as an adjunct was attempted and resulted in successful healing of the fistula. This patient is on follow-up for 3 years and is asymptomatic.[18] After this successful healing of difficult fistula, PRF has been used as a routine adjunct to VAAFT in our unit. When the confounding factors were eliminated, there was statistically significant effect and lower recurrence rates, when PRF was used as an adjunct in comparison to fibrin glue as an adjunct. Time for healing of fistula as well as complication rates (infection/bleeds/perforation) was comparable between the two groups. Lower rates of failure and a reduced need for second procedure were noted when PRF was used as an adjunct. The use of PRF as an adjunct also seemed to give better results in treating recurrent fistula.

PRF was also found to be economical at 300 (INR [Indian rupees]), in comparison to Fibrin glue priced at 11,000 (INR). VAAFT procedure with either adjunct has given earlier and better healing of fistula in comparison to the conventional fistulectomy or seton procedures.[1011] In most procedures for fistula, the risk factors for recurrence are the anatomy of the fistula, comorbidities, inadequate assessment of the fistula preoperatively, incorrect choice of procedure, surgical inexperience and incomplete procedure.[19] This is especially true in patients being considered for conventional procedures like Seton or Fistulectomy. In our study recurrence following VAAFT was not dependent on fistula characteristics since the tract could be identified, mapped, explored and treated adequately. The adjuncts added to the success of the procedure. When the two adjuncts were considered individually, we found that use of PRF gave lower recurrence rates and was more economical in the short and medium term. Long-term results are awaited. For an economically strapped nation, this has potential to improve treatment strategies in the management of fistula and give less morbid, better, and cheaper alternatives to the standard fistulectomy or seton placement.


This is a retrospective study of all patients who underwent VAAFT for 5 years, hence randomisation was not possible. A prospective randomised control study is being planned to compare the efficacy of fistulectomy, VAAFT with fibrin glue and VAAFT with PRF.


Both adjuncts are safe and effective when used in the treatment of fistula-in-ano. PRF is more effective with lower recurrence rates and is economical when compared to Fibrin glue as an adjunct to VAAFT.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


  1. Dr. Veena Shenoy, Department of Transfusion Medicine, for helping us with the preparation of PRF
  2. Anaesthesia and Nursing staff for their constant support
  3. Department of Biostatistics.


Appendix 1: Video assisted anal fistula treatment – Platelet rich fibrin versus fibrin Post-operative questionnaire


Mrd No. Type of adjunct used: Fib/PRF

  1. How long has it been since your surgery?
  2. How much time did it take for the discharge and other symptoms to reduce after the surgery?
  3. Have you had any symptoms after the surgery? Yes/No
No title available.


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Fistula; operative procedure; platelet-rich fibrin; video-assisted anal fistula treatment

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