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 Table of Contents  
ORIGINAL RESEARCH REPORT
Year : 2019  |  Volume : 16  |  Issue : 4  |  Page : 133-137

Two component preparation of fibrin glue and its clinical evaluation in split skin grafting


1 Department of Urology, Narayana Medical College and Hospital, Nellore, Andhra Pradesh, India
2 Department of Plastic Surgery, Apollo Health City, Jubilee Hills, Hyderabad, India

Date of Web Publication22-Oct-2019

Correspondence Address:
Dr. Guru Prasad Reddy Gorla
Department of Plastic Surgery, Apollo Health City, Jubilee Hills, Hyderabad - 500 033, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcls.jcls_33_18

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  Abstract 

Background: Fibrin glue is an alternative to conventional suturing and stapling of skin grafts and has several advantages. It acts as a sealant and a hemostatic agent with an added adhesive property that has been reportedly used in many specialties with better outcomes. Objective: The objective was to study the effectiveness of fibrin glue in anchoring the split skin graft to the wound bed and to analyze the advantages, disadvantages, and outcome of using fibrin glue compared to suturing and stapling. Methodology: A total of 60 patients undergoing split skin grafting for various indications were studied. Each patient was used as both case and control, where fibrin glue was applied on one half and sutures and/or staples were applied on the other half of the same ulcer. Examination of the wound was conducted by two observers independently from the 3rd postoperative day at regular intervals onward and included inspection for the graft uptake, soakage, and infection and graded accordingly based on the three parameters. Results: Overall, graft uptake was better in fibrin glue study group. Furthermore, soakage and infection were less in fibrin glue study group when compared to the conventional suturing/stapling. No difference in infections rate was found among burns and postsurgical raw area patients. Conclusion: The use of fibrin glue is a simple, safe, and cost-effective method, with a rapid technique to fix the skin graft, avoid peroperative bleeding and postoperative collection, better uptake of graft, and better overall results.

Keywords: Burns, diabetic ulcer, fibrin glue, skin graft


How to cite this article:
Pavan A P, Gorla GP. Two component preparation of fibrin glue and its clinical evaluation in split skin grafting. J Clin Sci 2019;16:133-7

How to cite this URL:
Pavan A P, Gorla GP. Two component preparation of fibrin glue and its clinical evaluation in split skin grafting. J Clin Sci [serial online] 2019 [cited 2019 Nov 13];16:133-7. Available from: http://www.jcsjournal.org/text.asp?2019/16/4/133/269718


  Introduction Top


With the exploding population and road traffic accidents, traumatic injury to the skin has also become very much common. With raising epidemic and India becoming the diabetic capital of the world, diabetic ulcer has been a common and challenging problem to avoid and treat.

Skin grafting came as a major breakthrough in treating ulcers and raw areas which cannot be closed primarily and is still evolving. This led to the evolution of skin grafting where the first autotransplantation of the skin was done by placing a 2–3 mm epidermal graft on a granulating wound.

Once the graft is harvested, it can be fixed to the recipient bed using good old conventional method of sutures and staples. Due to the difficulties, disadvantages, and skill, it mandated for the conventional methods of sutures and stapling the graft. The idea of developing the tissue adhesive was then floated. Bergel first reported the use of fibrin as the biological adhesive, but Tidrick and Warner first used the fibrin glue for fixing skin grafts.[1]

Fibrin glue is an alternative to conventional suturing and stapling of skin grafts and has some added advantages. Conventional methods had some demerits such as foreign body reaction, scarring, infection, and pain during removal and was expensive too, whereas the use of fibrin glue is simple, safe, and cost-effective method,[2],[3] with a rapid technique to fix the skin graft, avoid per-operative bleeding and postoperative collection, better uptake of graft, and better overall results.

Biological fibrin glue initiates the final coagulation cascade when human fibrinogen is activated by thrombin. Fibrin glue is a sealant and a hemostatic agent with an added adhesive property that has been reportedly used in many specialties with better outcomes.[3],[4],[5]

Many techniques have been developed to produce fibrin which is commercially available and these have their own risks, expensive, cumbersome, and time-consuming. In this study, fibrin glue which we have advocated includes cryoprecipitate, which is a rich source of fibrinogen and thrombin from screened healthy donor's fresh-frozen plasma (FFP) is less time-consuming, cost-effective, and safe; and the same has been used in 30 patients admitted in Coimbatore Medical College and Hospital, Coimbatore. This study compares the effectiveness of fibrin glue with conventional sutures and staples.


  Methodology Top


Patients admitted in the General Surgery and Plastic Surgery Departments in a Medical College Hospital undergoing split skin grafting were studied over a period of 1 year. Patients undergoing split skin graft for diabetic ulcers, traumatic ulcers, and burns were included in the study.

Antibiotics were started, as a part of preoperative treatment in all patients undergoing split skin grafting. Peroperatively, each patient was used as the case and control, where fibrin glue is applied on one half and sutures and/or staples are applied on the other half of the same ulcer.

Examinations of the graft for anchorage were considered and graded satisfactory or not. Examination of the wound was started from the 3rd postoperative day onward and included inspection for the graft uptake, soakage, and infection. Fourteenth day scores by both the two observers for all the parameters were taken. Examination was continued for a minimum of 2 weeks, and the scoring was done by assessing the following three parameters, namely graft take, soakage, and infection.

Average of the 14th-day score given by both the observers for each parameter will be taken into account.

The wound beds of all the 60 patients included in the study were prepared well before the surgery. Once the granulation tissue was adequate, and pus culture and sensitivity report showed no growth/microbial load <105/g of tissue, the cases were posted for surgery.

Cryoprecipitate was used since it is a rich source of fibrinogen. It was prepared according to the method described by Armand J Quick. This was obtained from the FFP of healthy donors screened negative for HIV and hepatitis B. About 100 ml of FFP was thawed to 2°C–4°C and was ten times diluted with distilled water, making 1000 ml of solution.

About 10 ml of 1% acetic acid was added to this to bring the pH 5.3, and this resulted in the formation of precipitate. It was kept for ½ h and then centrifuged at 3000 rpm for 5 min.

The precipitate was collected, and in this, normal saline was added to make it 100 ml and then pH was brought up to approximately 7 by titrating with sodium carbonate. This was put in a water bath (37°C), and 1 ml of 0.1 M calcium chloride was added. The clot which formed in 45–120 s was removed by wrapping it around a stirring glass rod. The thrombin solution thus prepared was water clear and was constant in potency. The strength of thrombin was standardized to 10 s of thrombin time with the help of full strength thrombin solution.

This thrombin solution was stored in deep freeze at <−20°C to maintain the potency and could be used up to a month. Once the components are prepared, they were stored in deep freezer and used when required. Cold chain was maintained. On the day of surgery, the components were taken out from the deep freezer and thawed to room temperature. Before surgery, the wound bed is prepared well. Adequate thickness of graft is harvested. One component is sprinkled over the bed and the other component on the graft is applied. Half of each skin graft is fixed with skin staples and the other half with fibrin glue [Figure 1].
Figure 1: Skin graft fixed with skin staples in one half and the other half with fibrin glue

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Once the graft is applied, it is checked for the anchorage by pulling it gently with forceps or moving the graft with hands and noted whether anchorage is satisfactory or not. Grafted limb is immobilized, and paraffin gauze is applied to the donor site. Subsequently in the postoperative period, graft is monitored for graft uptake, soakage, and infection by the observers and results are tabulated. [Table 1], [Table 2], [Table 3], [Table 4].
Table 1: Scale I: Graft take

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Table 2: Scale II: Soakage

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Table 3: Scale III: Infection

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Table 4: Postoperative follow-up

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  Results Top


A total of 60 patients were included in the study. Sex distribution showed a male predominance with two-third of patients in the study being male. Majority of the patients shared diabetes or trauma as the underlying etiology with burns and others contributing to a minority [Figure 2].
Figure 2: Bar chart showing etiology of the raw area

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Most of the patients were in the age group of 51–60 years which accounts for 33.3% and least among 71–80 years accounting for 6.66%. Others contributed to 60% of the study population. [10% between ages 31–40 years, 30% of ages 41–50 years and 20% between 61–70 years] [Table 5].
Table 5: Age distribution of the patients

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Among diabetic patients, graft uptake was 10% better, 13.46% less soakage, and 16.36% less infectious when compared with the control group [Figure 3]. In hypertensive patients, graft uptake was better by 5.67% and superiority among soakage and infection with 7.7% less soakage and 7.7% less infection [Figure 4].
Figure 3: Graft uptake in diabetic patients

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Figure 4: Graft uptake in hypertensive patients

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When posttraumatic raw area group was considered, graft taken was 3.28% better with 2.33% less soakage and 6.53% less infection. Although the anchorage was not so satisfactory among the burns patients, graft uptake was 4.35% better, 12.5% less seroma formation when compared to the control group. However, no difference in infection was found among both the groups.

In postsurgical raw area patient, no difference in soakage and infection was found, but the graft uptake was significantly better by 14.29% [Figure 5].
Figure 5: Graft uptake in postsurgical raw area patients

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Overall, graft uptake was better in fibrin glue study group (P = 0.01). Furthermore, soakage and infection were significantly less in fibrin glue study group (P = 0.01 and 0.001, respectively) when compared to the conventional suturing/stapling.


  Discussion Top


Wound healing by primary intention is the most desirable one. This has been the challenge for surgeons to achieve these feet since ages. To overcome this, sutures were developed, but the expectations and dream of developing an ideal suture were not completely fulfilled. Hence, the search for alternatives kept going on, and that's when tissue adhesives were created. Today, we have both biological (fibrin glue) and synthetic (cyanoacrylate) tissue adhesives.

In our study, we have used fibrin glue as a tissue adhesive for fixing split skin grafting. The principle behind using fibrin glue as tissue adhesive is born from the concept that the first phase of inflammation involves formation of thrombus through a series of events that takes place in coagulation cascade. In our study, we have used fibrin glue that is of human origin and bypassing the problem of anaphylactic reaction, which is encountered when fibrin glue of bovine origin is used.

The process of using fibrin glue in our setting was easy and comfortable, only loose string is preparation of thrombin from FFP. Once thrombin is prepared, it is stored under −20°C to maintain the potency and can be used over a month. This helped to overcome the difficult and cumbersome method of conventional suturing and pain associated with stapling.

Of the 60 patients in our study, diabetes mellitus dominated the strength of patients accounting for 33%, of which 26.4% were male and 6.6% were female, indicating the shift of diabetic epidemic toward India.

Strength of trauma in our study was 26.66%, with males being 19.99% and females being6.66%.

Hypertension association in our study was 23.33% with male population being 16.66% and females making up to 6.66%.

Only eight burns patients participated in the study, of which 75% were female and one male patient with one postmastectomy raw area patient in the study.

Anchorage was satisfactory in 83.33% of the cases, except for burns patients and one patient with hypertension, where anchorage was not satisfactory. Anchorage in our study was comparable to the study done by Saxena et al.[6] in fixing split skin grafting/flaps using fibrin glue. The results were consistent and satisfactory when compared to this study. Anchorage of the graft to bed was rapid, the time consumed for the procedure was very short when compared to conventional suturing and/or stapling, these can be corroborated with those of Bercial et al.[7]

Graft uptake in our study is similar to the study conducted by the Saxena et al.[6] The findings in our study also corroborate with those of de Moraes et al.,[8] where fibrin glue was used for skin grafting and the second intention wound healing following dermatologic surgeries like excision of malignant epithelial cutaneous tumors.

Soakage in our study among cases was very less when compared to the control group. These findings were comparable to Saxena et al.'s [6] study. According to the study conducted by the Bercial et al[7], there is further evidence that when fibrin glue was used as a sealant in abdominoplasty, seroma and soakage were less. According to the study by Milic et al.,[9] fibrin glue can be used as sealant to prevent pocket-related complications in patients undergoing pacemaker transplantations. This shows that fibrin glue is a very good sealant or a hemostatic agent; seroma formation following its application will be very minimal. There are enough literature and studies to show that it is very efficacious as a sealant.[8],[9]

Even though diabetic patients are prone for infections, infection rate among diabetic patients was less in fibrin glue study group following grafting. This can be corroborated to those of study conducted on rats by Jabs et al.,[10] where they inoculated wound with staphylococcus and grafts were placed. The graft was still better among infected wounds.[11]

In our study, no difference in infections rate was found among burns and postsurgical raw area patients.


  Conclusion Top


Graft uptake, soakage, and infection rate among all the patients in the fibrin glue group were better and satisfactory compared to control group with no difference in infection rate among burns and postsurgical raw area patients and no difference in soakage in postsurgical raw areas leading us to a conclusion that fibrin glue is advantageous compared to sutures or staples.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Saltz R, Sierra D, Feldman D, Saltz MB, Dimick A, Vasconez LO. Experimental and clinical applications of fibrin glue. Plast Reconstr Surg 1991;88:1005-15.  Back to cited text no. 1
    
2.
Stechison MT. Rapid polymerizing fibrin glue from autologous or single-donor blood: Preparation and indications. J Neurosurg 1992;76:626-8.  Back to cited text no. 2
    
3.
Stuart JD, Morgan RF, Kenney JG. Single-donor fibrin glue for hand burns. Ann Plast Surg 1990;24:524-7.  Back to cited text no. 3
    
4.
Toma AG, Fisher EW, Cheesman AD. Autologous fibrin glue in the repair of dural defects in craniofacial resections. J Laryngol Otol 1992;106:356-7.  Back to cited text no. 4
    
5.
Mouritzen C, Drömer M, Keinecke HO. The effect of fibrin glueing to seal bronchial and alveolar leakages after pulmonary resections and decortications. Eur J Cardiothorac Surg 1993;7:75-80.  Back to cited text no. 5
    
6.
Saxena S, Jain P, Shukla J. Preparation of two component fibrin glue and its clinical evaluation in skin grafts and flaps. Indian J Plast Surg 2003;36:14-7.  Back to cited text no. 6
  [Full text]  
7.
Bercial ME, Sabino Neto M, Calil JA, Rossetto LA, Ferreira LM. Suction drains, quilting sutures, and fibrin sealant in the prevention of seroma formation in abdominoplasty: Which is the best strategy? Aesthetic Plast Surg 2012;36:370-3.  Back to cited text no. 7
    
8.
de Moraes AM, Annichino-Bizzacchi JM, Rossi AB. Use of autologous fibrin glue in dermatologic surgery: Application of skin graft and second intention healing. Sao Paulo Med J 1998;116:1747-52.  Back to cited text no. 8
    
9.
Milic DJ, Perisic ZD, Zivic SS, Stanojkovic ZA, Stojkovic AM, Karanovic ND, et al. Prevention of pocket related complications with fibrin sealant in patients undergoing pacemaker implantation who are receiving anticoagulant treatment. Europace 2005;7:374-9.  Back to cited text no. 9
    
10.
Jabs AD Jr., Wider TM, DeBellis J, Hugo NE. The effect of fibrin glue on skin grafts in infected sites. Plast Reconstr Surg 1992;89:268-71.  Back to cited text no. 10
    
11.
Buckley RC, Breazeale EE, Edmond JA, Brzezienski MA. A simple preparation of autologous fibrin glue for skin-graft fixation. Plast Reconstr Surg 1999;103:202-6.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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