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ORIGINAL ARTICLE
Year : 2019  |  Volume : 22  |  Issue : 4  |  Page : 546-552

Comparison of the effect of advanced platelet-rich fibrin and leukocyte- and platelet-rich fibrin on outcomes after removal of impacted mandibular third molar: A randomized split-mouth study


Department of Oral and Maxillofacial Surgery, Near East University Faculty of Dentistry, Nicosia, Mersin-10, Turkey

Date of Acceptance28-Dec-2018
Date of Web Publication11-Apr-2019

Correspondence Address:
Dr. M G Caymaz
Near East University, Yakin Dogu Bulvari Post Code: 99138, Nicosia, Mersin-10
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_473_18

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   Abstract 


Aim: In this study, it was aimed to investigate and compare the postoperative effects of leukocyte- and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) in terms of pain, swelling, and trismus after mandibular third molar surgery. Subjects and Methods: The study included a total of 27 patients with bilateral impacted mandibular third molar, which surgically operated at different times. Patients were evaluated in two randomly separated groups. For the first and second group, A-PRF and L-PRF were applied into the tooth socket, respectively. The outcome variables were pain, swelling, the number of analgesics taken, and trismus. These variables were also assessed based on first, second, third, and seventh days following the operation. Statistical Analysis Used: The data were collected and analyzed with unpaired Student's t-test and Mann–Whitney U test. Results: The study was conducted with 27 patients, consisting of 15 females and 12 males between ages of 18–26. The visual analog scale pain scores of the L-PRF group during first (P < 0.05), second, and third days and total values (P < 0.01); the number of analgesics on days 2 (P < 0.01) and 3; and their total values (P < 0.05) were significantly higher than the A-PRF group. There was no significant difference between swelling, trismus, and the duration of operation (P > 0.05). Conclusion: The results of this study showed that the use of A-PRF after mandibular third molar extraction significantly reduces postoperative pain and the patients need to take analgesics of A-PRF group compared to L-PRF group.

Keywords: Advanced platelet rich fibrin, impacted third molar surgery, leukocyte- and platelet rich fibrin


How to cite this article:
Caymaz M G, Uyanik L O. Comparison of the effect of advanced platelet-rich fibrin and leukocyte- and platelet-rich fibrin on outcomes after removal of impacted mandibular third molar: A randomized split-mouth study. Niger J Clin Pract 2019;22:546-52

How to cite this URL:
Caymaz M G, Uyanik L O. Comparison of the effect of advanced platelet-rich fibrin and leukocyte- and platelet-rich fibrin on outcomes after removal of impacted mandibular third molar: A randomized split-mouth study. Niger J Clin Pract [serial online] 2019 [cited 2019 Apr 23];22:546-52. Available from: http://www.njcponline.com/text.asp?2019/22/4/546/255931




   Introduction Top


Throughout different studies, various results show that the most frequent tooth to experience a case of impact is the third molar tooth and this proportion constituted 98% of all impacted teeth.[1] Thus, surgical removal of the impacted third molar tooth is one of the most common procedures in the oral and maxillofacial surgeries.[2] In postoperative period following the removal of impacted mandibular third molar tooth, patients usually complain about complications including but not limited to pain, swelling on the cheek, trismus, and secondary bleeding.[3],[4] As inflammatory complications still exist as an issue, various attempts have been made to reduce these complications and to accelerate postoperative recovery period.[5] These attempts include platelet-rich plasma application, using high or low-speed rotary instruments for osteotomy, cryotherapy, postoperative ice packs, and laser.[6],[7],[8],[9],[10] In addition to these attempts, platelet-rich fibrin (PRF) applications have begun to be used in the recent years.[11] In a previous study, placement of leukocyte- and platelet-rich fibrin (L-PRF) after surgical mandibular third molar tooth extractions has been shown to reduce both the pain and total number of analgesics taken during the postoperative period.[11]

L-PRF is a blood derivative that is obtained by centrifuging the patient's own blood, which contains autologous platelets, growth factors, cytokines, and leukocytes that play a key role in tissue regeneration, which enables extracellular matrix synthesis, cell proliferation and differentiation, angiogenesis, and occurrence of chemotaxis.[12] L-PRF consists of close combination of cytokines contained in a fibrin network, glucan chains, and structural glycoproteins and is considered as the second generation of platelet concentrates.[13] Choukroun et al. are considered as the pioneers of PRF utilization.[14]

Choukroun et al. produced an improved PRF form which contains greater number of white blood cells and named it advanced platelet-rich fibrin (A-PRF).[15] Leukocytes have been shown to be very important immunocytes capable of directing various cell types in the healing process of the wound.[16],[17] The fact that high centrifugal forces shift cell populations to the bottom of collection tubes, it has recently been assumed that an increase in leukocyte counts in the PRF matrix can be achieved by reducing the centrifugal g-force.[18] Since then, an increment of total leukocyte count has been observed in the PRF matrix constructs (now called advanced PRF or A-PRF) by decreasing centrifugal g-force.[18] Having said that, in accordance to this hypothesis, the release of several growth factors in A-PRF was found significantly higher compared with L-PRF and PRP.[19]

During this study, the postoperative effects of L-PRF and A-PRF were compared in terms of pain, swelling of the cheek, and trismus after surgical extraction of mandibular third molar tooth. This study bears the distinction of being the first clinical study to compare the postoperative effects of L-PRF and A-PRF after surgical mandibular third molar tooth extractions.


   Subjects and Methods Top


This prospective, randomized, split-mouth study was conducted between November 2017 and May 2018 in Nicosia, Turkey. A total of 27 patients (15 female, 12 male) aged 18–26 were included in the study. This study followed the Declaration of Helsinki in terms of medical protocols and ethics. The protocol design was approved by the Near East University Scientific Research Ethics Committee (project number NEU/2017/51-462). All patients were informed about the surgical procedure, postoperative period, and possible complications and a written consent was obtained from every participants.

The selection criteria of the patients were as follows: (a) age ≥18; (b) the presence of bilaterally symmetrically impacted mandibular third molar, which requires an extraction for prophylactic reasons; (c) absence of systemic diseases; (d) not using chronic opioid; (e) not being pregnant; (f) not smoking and no alcohol usage; and (g) the absence of allergy to penicillin or any other drugs used during standardized postoperative therapy. All patients were classified as physical status I using the guidelines of the American Society of Anesthesiologists. Some cases, in which the tooth could not be completely removed and needed to be sectioned during the operation, were excluded from the study. Additionally, the cases with the operation time exceeding 30 min, the cases with severe periodontal disease or acute pericoronitis, the cases using antibiotics for an existing infection, and the cases not capable of following postoperative instructions were excluded from the study. Thereby, only the patients having vertical and bilaterally symmetrical (in the same position on both sides) full impaction of third molar tooth were included. All patients were selected according to the similar surgical conditions in terms of the relation of inferior alveolar nerve, ramus, depth of impaction, and position of the tooth relative to the jaw bone. Osteotomy is a necessity for all selected patients. According to the classification system of Pell and Gregory, extractions of mandibular third molar are of moderate difficulty operations (class I, level C).[20]

Patients were randomly separated into two groups. In each group, conventional methods were used to perform the extraction. For the first group, A-PRF was applied to the tooth socket (n = 27). For the second group, L-PRF was applied to the tooth socket (n = 27). The operation sides (left or right) to be carried out first and the material (A-PRF or L-PRF) to be placed on the specified side were determined in an objective and random fashion, using a toss of heads or tails. Between the first and second operations, a minimum waiting period of 21 days was agreed upon in order to ensure the parameters to be examined returned to the preoperative period.

Preparation of A-PRF and L-PRF Clot

A-PRF was prepared according to the method described by Ghanaati et al.[18] and L-PRF was prepared according to the technique described by Dohan et al.[13] Approximately 10 min prior to surgery, blood samples collected in 10 ml of vacuumed plain glass tubes (A-PRF+ by Choukroun: Jiangsu Kangjlan Medical Apparatus Co. Ltd, Jiangyan City, Jiangsu, China) were centrifuged (Elektro-mag M415P, Istanbul, Turkey) for 14 min at 1500 rpm without anticoagulant agents in order to obtain A-PRF and in 10 ml of glass coated plastic tubes (BD Vacutainer Clot Activator Tube, BD, Belliver Industrial Estate, Plymouth, UK) were centrifuged (Elektro-mag M415P, Istanbul, Turkey) at 3000 rpm (approximately 400g) without anticoagulant agents for 10 min in order to obtain L-PRF. In each process, platelet-poor plasma was disposed of the tubes. The resulting clots, including all thrombocytes that may be localized under the junction between the clot and the red blood cells, were dissected 2 mm below the contact point of red blood cells at the bottom.[21] For each patient, a sufficient amount of A-PRF or L-PRF was produced from 10 ml tube in order to fill each extraction socket.

Surgical procedure

Radiologic examination including panoramic radiography of each patient was performed and all were treated by the same assistant and surgeon. Surgery was performed using nerve block agents containing 40 mg/ml articaine HCl and 0.012 mg/ml epinephrine HCl (2 ml Ultracaine DS Forte; Sanofi Aventis) on lingual, inferior alveolar, and buccal nerves under local anesthesia. In each group, the full thickness mucoperiosteal flap incision (Archer flap) was performed in a triangular shape in order to prevent the possible involvement of muscle tissue. During both surgeries, the surgeon applied the same approach by only replacing the instruments used. After elevation of the mucoperiosteal flap, in each group in the similar fashion (A-PRF and L-PRF), the osteotomy was performed using W and H Implantmed (W and H Dentalwerk Bürmoos GmbH, Bürmoos, Austria) surgical high-speed hand piece and 1.6 mm round bur under abundant irrigation and at 40,000 rpm. The tooth was loosened with a root elevator. After removal of the tooth, the A-PRF or L-PRF was placed into the socket.

In all cases, a sterile physiological saline solution containing no antibacterial agent was used to clean the cavity left from the extraction; then, A-PRF or L-PRF was placed inside the tooth socket followed by closing the wound with 3-0 silk suture (four stitches). A gauze pad was placed in the surgical area and the patient was asked to bite on for 30 min. Stitches were removed after 7 days. Immediately after the operation, an ice pack was given to the patient to apply every 10 min for 6 h. No pharmacological treatment or antibiotic was given to the patients before the operation. Some postoperative instructions were given to all patients: They were informed to do a 24-h soft and cold diet, to take amoxicillin + clavulanic acid (GlaxoSmithKline, Augmentin BID 1000 mg tablet) twice a day for 5 days and to use a mouthwash containing antiseptic (povidone–iodine 7.5%) three times a day for 7 days. Acetaminophen (500 mg) for postoperative period was inscribed (once in every 4–6 h, 500 mg) for the patients in case of any pain.

Evaluation procedure

For the postoperative period, the pain was evaluated with the help of the visual analog scale (VAS) ranging from 0 (no pain) to 10 (most severe pain).[22] VAS has proven to be a sensitive and reliable method that is widely used and applied to record pain after an oral surgery.[11],[23],[24],[25] The number of consumed analgesic tablets was also recorded.

Trismus, as defined by Üstün et al., was assessed by measuring the distance between the mesioincisal corner of the maxillary and mandibular right incisors, whereas mouth was fully opened.[26] In order to record swelling, a modification of the tape measurement method developed by Gabka and Matsumara was used.[26],[27] Three preoperative measurements were done between the following five reference points: the lateral aspect of the eye, mandibular angle, soft tissue pogonion, tragus, and outer corner of the mouth. Each patient was evaluated in order to obtain measurements on the first, second, third, and seventh days after the operation. The difference between the baseline value and each postoperative measurement was used to determine trismus and facial swelling for those day.[26] Daily changes were recorded in the percentage format.

The operation time was considered to be the time between the start of the incision and the termination of the suture. All preoperative and first, second, third, and seventh day postoperative measurements were acquired approximately at the same time for every individual.

Statistical analysis

Group comparison of VAS pain scores, swelling, and trismus was performed using unpaired Student's t-test and Mann–Whitney U test was used for intergroup comparisons for the number of analgesics taken. Values of P < 0.05 were taken in order to show statistical significance. Data are presented as the mean ± standard deviation or median (min–max). Statistical analyzes were done using the GraphPad Prism software package (ver. 8).


   Results Top


Patient demographics

Between November 2017 and May 2018, a total of 60 teeth of 30 patients (16 female, 14 male) were extracted. In total, three patients were excluded from the present study because two patients did not attend follow-up period and infection occurred in one patient. A total of 27 patients, ranging in age from 18 to 26, were included in the study. Patients were randomly separated into two groups. In each group, conventional methods were used to perform the extraction. For the first group, A-PRF was applied to the tooth socket (n = 27). For the second group, L-PRF was applied to the tooth socket (n = 27). The study was stopped for the thought that enough number of patients reached. Pain, taking number of analgesic, trismus, and swelling were examined in all of 27 patients at the total of 54 tooth extractions. There were no important harms or unintended effects in each group.

Results of visual analog scale pain scores

When the VAS pain scores of L-PRF and A-PRF applications were assessed in patients who underwent impacted mandibular third molar tooth surgery, VAS pain scores were significantly higher in L-PRF group than the ones in A-PRF group during first (P < 0.05), second, and third days and total values (P < 0.01). On the seventh day, there was no significant difference between A-PRF and L-PRF groups in terms of VAS pain scores (P > 0.05) [Table 1].
Table 1: The visual analog scale (VAS) pain scores of leukocyte- and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) applications in patients that underwent impacted mandibular third molar surgery

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Results number of analgesics taken by the patients

The number of analgesics taken by the patients was significantly higher in the L-PRF group than the A-PRF group on days 2 (P < 0.01) and 3 and total values (P < 0.05). On days 1 and 7, there was no significant difference between A-PRF and L-PRF groups in terms of the number of analgesics (P > 0.05) [Table 2].
Table 2: The number of analgesics taken by the patients for leukocyte- and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) applications in patients that underwent impacted mandibular third molar surgery

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Results of the swelling values

When the swelling values were examined, there was no significant difference between groups A-PRF and L-PRF on days 1, 2, 3, and 7 (P > 0.05) [Table 3].
Table 3: The swelling values for leukocyte- and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) applications in patients that underwent impacted mandibular third molar surgery

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Results of trismus values

When trismus values were examined, there was no significant difference between groups A-PRF and L-PRF on days 1, 2, 3, and 7 (P > 0.05) [Table 4].
Table 4: The trismus values for leukocyte- and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) applications in patients that underwent impacted mandibular third molar surgery

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Results for operational periods

There was no significant difference between the groups A-PRF and L-PRF when the duration of operation was evaluated (P > 0.05) [Table 5].
Table 5: The duration of operation for leukocyte- and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) applications in patients that underwent impacted mandibular third molar surgery

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   Discussion Top


Mandibular third molar tooth extraction is a commonly used procedure in the area of oral surgery. Manifold postoperative complications may be seen which may disturb patients and reduce their quality of life. For this reason, clinical trials are necessary to define methods for improving the quality of life for the patient after the surgery.[28] The primary aim of this study is comparative evaluation of postoperative effects of L-PRF and A-PRF placed into the tooth socket after surgical extraction of mandibular third molar tooth with a minimum of 21 days interval. No existing clinical studies evaluate the effect of A-PRF in terms of pain, total number of painkillers, swelling on the cheek, and trismus after the extraction of mandibular third molar tooth. Moreover, there are no clinical studies in the literature comparing the effects of L-PRF and A-PRF about pain, total number of painkillers taken, swelling of the cheek, and trismus after the extraction of the mandibular third molar tooth.

Different results have been reported in the literature about the effects of L-PRF on postoperative pain, swelling on the cheek, and trismus after third molar tooth surgery. In some studies, no significant difference in PRF affecting pain was seen.[23],[24] Other similar studies have reported that PRF has a significant positive effect on pain.[11],[25] In this study, the effect of A-PRF on pain according to L-PRF after mandibular third molar tooth surgery was evaluated.

Due to the consequences of the first animal experiment for A-PRF, it was found that PRF had a dense and stable fibrin structure which is more resistant to cellular penetration and that A-PRF facilitates cellular penetration as it has a more porous structure, thus allowing the endothelial cells to migrate easily into the structure and induce angiogenesis more rapidly.[29] It is also shown in a study that no significant difference in Vaskular endothelial growth factor (VEGF) of these two protocols and may have contributed significantly to higher vascularization in A-PRF than in other factors involved in angiogenesis.[29],[30]

The vibrations of the A-PRF centrifuge have proven to lead to a smaller clot and membrane formation.[31] The same centrifuge device (Electro-mag M415P, Istanbul, Turkey) was used in this study to neutralize the centrifuge vibration variables in both L-PRF and A-PRF produced. The main difference that can explain the size of the clots and the differences in the biological signature of the membranes are mostly associated with centrifugal forces, the change in protocol as well as with the time of proprietary-type centrifuge tubing and centrifugation.

In a study conducted earlier, it was shown that the manufacture of L-PRF platelets was not affected by the use of glass-coated plastic tubes or glass tubes.[32] For this reason, diversity of the tubes between L-PRF and A-PRF may not explain the observed differences. As a result, these differences in size, biological signature, and appearance of the membranes and clots between the original A-PRF and L-PRF could possibly be related to the change in centrifugal forces.

Several methods have been used to measure facial swelling.[26] Our method is the modification of Gabka and Matsamura's tape measurement method defined by Üstün et al.[26] This method uses numerical data that provide us noninvasive, simple, cost-effective, and time-saving soft tissue contour changes, although it is not as accurate as magnetic resonance imaging or computed tomography scan and is not capable of making precise measurements of facial soft tissue volume. In this study, there was no significant difference in terms of swelling between the techniques used.

The position of the tooth may also alter the possibility complications. For this purpose, patients with bilateral symmetrically impacted teeth were selected. Operations were performed in two sessions with 21-day interval. The degree of surgical difficulty was evaluated according to the position of third molar tooth and anatomic factors (ramus relationship and depth of inclusion) determined on radiological data. According to the classification system of Pell and Gregory, extractions of mandibular third molar are of moderate difficulty (class I, level C).[20] This condition was considered as criteria for inclusion to obtain adequate homogeneity between two groups and to reduce the risk of confounding factors.

Not only anatomic factors but also flap design, bone cutting, time spent for surgical procedures, use of rotary instruments, and surgeon-related factors are responsible from incidence of complications. In this study, the flap design was triangular in all extractions and there was no statistical difference between the operation times (P > 0.05). All surveys and extractions were performed by the same surgeon to ensure the homogeneity between each group. In addition, the operative side and age distributions of the surgical groups were homogeneous as well.


   Conclusion Top


In conclusion this study showed that the use of A-PRF after mandibular third molar extraction significantly reduced postoperative pain and showed the need for analgesic for the patients of A-PRF group compared to L-PRF group. However, there was no significant difference between groups in terms of swelling and trismus (P > 0.05). In order to obtain more meaningful results, a larger group of individuals must be used in future studies with different evaluation methods for all variables.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

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



 

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