Efficacy of Platelet‐Rich Plasma in Post‐Tonsillectomy Wound Healing and Pain Management: A Randomized Controlled Study

ABSTRACT

Background

Tonsillectomy is one of the most common surgical procedures in otolaryngology, but the healing process remains unknown in individual patients. Several interventions, including platelet‐rich plasma, have been investigated to improve healing and pain control due to their regenerative properties.

Objective

To assess the effect of platelet‐rich plasma injection during tonsillectomy on postoperative results especially on epithelization stage and postoperative pain.

Method

A prospective randomized controlled trial was conducted between January 2023 and December 2024, including 19 patients with platelet‐rich plasma randomly injected in one of the fossae [treatment group] and normal saline in the other fossa [control group]. The endpoints were the epithelialization stage and pain score on days 1–7 after tonsillectomy.

Results

There were no statistically significant differences between groups in the postoperative epithelization stage. At the treatment sites, grade III wound epithelization was 21.1%, compared with the control site, where none had grade III wound epithelization. The p‐values for wound epithelization (0.903) and pain score (0.222) indicate no difference between groups. Both groups' pain scores improved over time (p < 0.001).

Conclusions

Intraoperative injection of platelet‐rich plasma into the tonsillar beds was effective in stimulating tonsillar wound healing. Because of its properties, the treatment group appeared to have faster wound recovery than the control group. However, the differences were not statistically significant. Further studies with larger sample sizes are warranted to elucidate the potential benefits of platelet‐rich plasma in post‐tonsillectomy healing.

Key Points

• Platelet‐rich plasma (PRP) has regenerative properties to improve the healing process in many procedures, including tonsillectomy.

• A prospective randomized controlled design compared PRP and saline within the same patient.

• PRP demonstrated a trend toward improved epithelialization, although this was not statistically significant.

• No significant difference in postoperative pain scores was observed between PRP and control sites.

• Further studies with larger sample sizes are required to determine the clinical benefit of PRP.

1. Introduction

Tonsillectomy is one of the most frequently performed surgical procedures in otolaryngology and is commonly used to treat recurrent tonsillitis or obstructive sleep apnea. Despite its frequency and surgical advancements, postoperative complications, including pain, haemorrhage, and poor oral intake, remain the main reasons for extended hospital stays and prolonged recovery [1].

The post‐tonsillectomy wound‐healing process in the tonsillar fossa remains poorly studied. A review article [2] proposed that wound healing occurs via secondary intention through the growth of keratinized squamous epithelium over the wound bed, as observed macroscopically. Wound healing can be divided into three stages: the early stage, characterized by soft tissue edema and some fibrin growth; the intermediate stage, with fibrin clots within the tonsillar fossae and granulation growth marking the beginning of epithelialization; and the late stage or remodelling phase, in which the epithelium progressively covers the entire tonsillar bed [2]. Factors affecting postoperative wound healing include surgical technique, with cold dissection and intracapsular tonsillectomy demonstrating faster healing times than electrocautery dissection; history of laryngopharyngeal reflux, which prolongs healing time because of the damage to the tonsillar fossae by reflux contents; and the use of adjunctive treatments, such as the use of topical autologous serum on the tonsillar bed, sucralfate to form a barrier over a wound, or hyaluronic acid to stimulate rapid wound healing [2, 3, 4, 5].

Autologous serum, especially platelet‐rich plasma (PRP), has been proposed to improve postoperative outcomes and wound healing and to decrease complications, owing to its regenerative and biostimulating properties [2, 6]. PRP has become recognized in the surgical field for its simple preparation method and safety for application. Since its introduction to open‐heart surgery in 1987, it has gained acceptance across surgical specialties. In ENT surgeries, PRP is applied in tympanoplasty to accelerate graft adhesion and reduce granulation [7]. PRP is the specific plasma layer separated from centrifuged blood, is rich in platelets, and contains many types of growth factors, such as platelet‐derived growth factor, vascular endothelial growth factor, and transforming growth factor, as well as cytokines. These components of PRP play a vital role in the wound‐healing process [8, 9].

PRP application on the resected tonsillar bed has been demonstrated to decrease postoperative haemorrhage and improve postoperative pain, enhancing patient recovery [10, 11, 12, 13, 14, 15]. However, some studies, such as those conducted on paediatric patients, have reported no significant effect of topical PRP on reducing postoperative pain or recovery time [16]. The results vary because, in most studies involving topical application of PRP on tonsillar fossae, PRP may not remain at the surface of the surgical wound for a long duration, which can be attributed to the dynamic wound environment. This may reduce the efficacy of PRP [14, 15, 16, 17].

A recent study proposed an interesting method of PRP injection into tonsillectomy wounds combined with platelet‐rich fibrin glue at surgical sites. This study reported a significant increase in wound healing and reduced postoperative pain [17].

To address the research gaps in the existing literature, this randomized controlled trial evaluated the benefits of PRP injection in enhancing wound healing and reducing postoperative pain in patients undergoing tonsillectomy, aiming to provide reliable evidence that can be adapted to the future care process.

2. Materials and Methods

2.1. Study Design and Ethics

This prospective randomized controlled trial was conducted at the Department of Otolaryngology at our hospital. The Human Research Ethics Committee of the hospital approved this study (Approval No. COA MURA2023/778). Written informed consent was obtained from the participants before they were enrolled in the study.

2.2. Participants

We included patients aged ≥ 18 years scheduled for tonsillectomy at the Department of Otolaryngology at our hospital. We excluded patients undergoing concurrent surgical procedures, having confirmed tonsillar malignancy, having bleeding disorders or thrombocytopenia (platelet count < 100 000/μL), having a history of acid citrate dextrose allergy, and those unable to comply with the study protocol.

2.3. Sample Size Calculation

The sample size was determined based on the proportion of patients with complete wound healing, as reported by Kara et al. [4].

2.4. Randomization and Blinding

A computer‐based randomization process was used to allocate each participant to two treatments within the same surgery. One tonsillar fossa was injected with PRP, whereas the other was injected with normal saline solution (NSS). The participants were blinded to the allocation sequence. Three independent assessors were also blinded to the intervention for each participant. Before the tonsillectomy procedure, the patients' relevant baseline characteristics were collected: age, sex, tonsillar size graded using Brodsky's classification [18], and surgical indication (chronic tonsillitis or sleep‐disturbance breathing).

2.5. Intervention

2.5.1. Preparation of PRP and Normal Saline

PRP was prepared using two‐step centrifugation (LC‐04C; ZENITH LAB) with a centrifuge machine by an operating room nurse serving as a research assistant. All procedures were performed under aseptic conditions. First, 10 mL of venous blood was collected from the patient's vein using a 22‐gauge needle on the morning of the operation day in the inpatient department. The blood sample was transferred into four acid citrate dextrose tubes, which were spun at 300× g for 5 min, separating them into three layers: erythrocytes and leukocytes at the bottom, a buffy coat with elevated platelet concentration in the middle, and platelet‐poor plasma at the top. The buffy coat and platelet‐poor plasma layers were carefully collected using a sterile needle and transferred to sterile tubes. A second spin was performed at 700× g for 17 min to create the PRP [19, 20]. One millilitre of this concentrated PRP was drawn using a sterile, wrapped syringe from the lower third portion. The PRP was immediately prepared for injection into the patient's tonsillar fossa. As the control treatment, another wrapped syringe was drawn with 1 mL of normal saline to inject into the other tonsillar fossa.

2.5.2. Surgical Procedure

All patients underwent a standard tonsillectomy procedure under general anaesthesia. Haemostasis was achieved through monopolar electrocauterization at a power setting of 20 watts. The operating surgeons were not part of the research team. Following resection, a within‐subject study was used, in which 1 mL. of PRP was injected into one tonsillar fossa using a multiple‐site injection technique (0.2 mL each in the superior, inferior, mid, medial, and lateral parts), while 1 mL. of saline was injected into the contralateral fossa in the same fashion, per randomization results. This approach was selected to distribute material widely throughout the tonsillar bed while limiting diffusion to the contralateral side.

2.6. Outcome Measurements

2.6.1. Primary Outcome: Wound Healing

To evaluate the wound healing of both tonsillar fossae, the oropharynx appearance was recorded with 0‐degree endoscopy on postoperative day 7 and is shown in Figure 1. Three independent assessors, blinded to the treatment allocation, evaluated wound epithelialization by reviewing the endoscopic images and graded them from I to IV as follows: grade I indicated that the wound was completely covered with fibrin or had epithelialization between 0% and 25%; grade II indicated epithelialization between 26% and 50%; grade III indicated epithelialization between 51% and 75%; and grade IV indicated near complete epithelialization (> 75%) or fully healed tonsillar fossa (100%).

FIGURE 1.

Endoscopic images following the 7th day of tonsillectomy. (A) Right‐sided tonsillar bed epithelization occurs in 50%. (B) Wound healing was assessed on both sides of the tonsillar bed. Comparative epithelization on the right side was 25%, and on the left side was 75%. Furthermore, (C) More fibrin covering the left‐sided tonsillar bed (epithelization 25%).

2.6.2. Secondary Outcomes: Pain Score

The secondary outcomes included postoperative pain assessment and analgesic consumption. Participants' postoperative pain levels were assessed using the 11‐point visual analog scale (VAS), a validated method in which participants rated their pain intensity on a scale from 0 to 10. Participants used the VAS to record their pain levels expressed by each side of the tonsil wounds on postoperative days 1–7 in the logbook provided. The dosage of analgesics used was also recorded.

2.7. Statistical Analysis

All data were analysed using StataCorp v18 (StataCorp LLC, College Station, TX, USA). Statistical significance was set at p < 0.05. For clinicodemographic data, categorical variables are presented as frequencies and percentages, whereas continuous variables are reported as means ± standard deviation or median (interquartile range [IQR]). Primary (wound healing grading on postoperative day 7) and secondary outcomes (VAS scores) were analysed with multilevel models. Interrater reliability was assessed using Cohen's kappa coefficient.

3. Results

We enrolled 19 participants: 5 men (26.3%) and 14 women (73.7%); their mean age was 34.5 ± 9.8 years. Most participants (n = 17, 89.5%) underwent tonsillectomy for chronic tonsillitis, and two (10.5%) underwent tonsillectomy for severe obstructive sleep apnea.

PRP was randomly injected into the left tonsillar fossa in 9 participants (47.4%) and the right tonsillar fossa in 10 (52.6%). Tonsil size grading was as follows: grade 1 (left: 10.5%, right: 15.8%), grade 2 (left: 57.9%, right: 52.6%), grade 3 (left: 26.3%, right: 31.6%), and grade 4 (left: 5.3%, right: 0%). Most procedures (n = 16) were performed by otolaryngology residents. The mean operative time was 63.1 ± 25.2 min. The median intraoperative blood loss was 10 mL (IQR: 10–20 mL). Two participants experienced postoperative bleeding and were admitted to stop bleeding in the operative room, both presenting on postoperative day 8 and day 13, respectively. Baseline characteristics and perioperative data are summarized in Table 1.

TABLE 1.

Demographic data and baseline characteristics of patients.

	n = 19
Age (years), mean ± SD	34.5 ± 9.8
Sex, n (%)
Male	5 (26.3)
Female	14 (73.7)
Platelet‐rich plasma site, n (%)
Left	9 (47.4)
Right	10 (52.6)
Tonsil grading, n (%)
Left
1	2 (10.5)
2	11 (57.9)
3	5 (26.3)
4	1 (5.3)
Right
1	3 (15.8)
2	10 (52.6)
3	6 (31.6)
Surgery indication, n (%)
CHT	17 (89.5)
Severe OSA	2 (10.5)
Surgeon, n (%)
Resident	16 (84.2)
Staff	3 (15.8)
Operative time (min), mean ± SD	63.1 ± 25.2
Blood loss (mL), median (IQR)	10 (10, 20)
Complication, n (%)	2 (10.5)

Abbreviations: CHT, chronic hypertrophy tonsillitis; OSA, obstructive sleep apnea.

A comparison of postoperative wound healing in PRP‐injected tonsillar fossae and NSS‐injected tonsillar fossae was conducted, and confounding factors, including sex, age, tonsil grade, and surgical indication, were controlled. Wound healing was assessed on postoperative day 7. At PRP‐treated sites, the distribution of wound healing grades was as follows: grade I: 42.1%, grade II: 36.8%, grade III: 21.1%, and grade IV: 0%. At the NSS‐treated sites, the distribution was as follows: grade I: 47.4%, grade II: 42.1%, grade III: 0%, and grade IV: 10.5%. No significant difference was observed in wound healing between the PRP and NSS groups (p = 0.903). Analysis of interrater reliability indicated fair agreement among the three independent raters. The kappa coefficient for wound healing assessments was 0.246 (95% CI: 0.066–0.411) for PRP‐treated sites and 0.257 (95% CI: 0.023–0.539) for NSS‐treated sites, demonstrating a high level of consistency across assessors (Table 2).

TABLE 2.

Wound‐healing assessment.

Epithelialization stage	PRP, n (%)	NSS, n (%)	p
I	8 (42.1)	9 (47.4)	0.903
II	7 (36.8)	8 (42.1)
III	4 (21.1)	0 (0.0)
IV	0 (0.0)	2 (10.5)
Kappa coefficient	0.246 (95% CI: 0.066–0.411)	0.257 (95% CI: 0.023–0.539)

Note: The Fisher's exact test for wound‐ healing assessment analysis.

Postoperative pain mean scores were recorded daily using the VAS between the PRP‐treated and NSS‐treated tonsillar fossae. On day 1, the mean VAS scores were 5.32 (0.46) and 5.16 (0.46), respectively (p = 0.722), for PRP‐treated and NSS‐treated tonsillar fossae; on day 7, the mean VAS scores were 2.68 (0.46) and 2.63 (0.46), respectively (p = 0.905), for PRP‐treated and NSS‐treated tonsillar fossae. No significant between‐group difference was noted in pain scores; however, a significant reduction in pain scores was noted in both groups between days 1 and 7 (p < 0.001). The daily pain score and average pain score are presented in Table 3 and Figure 2.

TABLE 3.

VAS pain score.

Time points	PRP mean (SE)	NSS mean (SE)	Mean difference (95% CI)	p
Day 1	5.32 (0.46)	5.16 (0.46)	0.16 (−0.71, 1.03)	0.722
Day 2	5.53 (0.46)	4.79 (0.46)	0.74 (−0.13, 1.61)	0.096
Day 3	4.21 (0.46)	3.95 (0.46)	0.26 (−0.61, 1.13)	0.553
Day 4	3.63 (0.46)	3.68 (0.46)	−0.05 (−0.92, 0.82)	0.905
Day 5	3.58 (0.46)	3.47 (0.46)	0.11 (−0.76, 0.97)	0.812
Day 6	3.47 (0.46)	3.00 (0.46)	0.47 (−0.40, 1.34)	0.285
Day 7 p‐Value	2.68 (0.46) < 0.001	2.63 (0.46) < 0.001	0.05 (−0.82, 0.92)	0.905
Total	4.06 (0.36)	3.81 (0.36)	0.24 (−0.15, 0.65)	0.222

Note: Data were analysed using mixed‐effect Poisson regression. Statistical significance level is set at 0.05 (α = 0.05).

FIGURE 2.

VAS pain score. Data were analysed with multilevel mixed‐effects linear regression. VAS score shows no difference between groups.

4. Discussion

The randomized controlled trial evaluated the effect of PRP injection on postoperative wound healing and pain following tonsillectomy. Our results revealed slightly higher grade III epithelialization rates in PRP‐treated sites; however, no significant differences in wound healing or epithelialization stage were observed between the PRP and control groups. Furthermore, the administration of PRP to the tonsilla fossae at the end of surgery did not affect the VAS pain scores. However, pain scores decreased over time in both groups. To control for confounding factors across groups that may affect wound healing, a within‐subject design was used; this technique also enhances statistical power while requiring a smaller sample size. Although cross‐side interference should be considered, intervention may influence the contralateral side, which could affect our outcomes. To reduce this effect, we considered the intralesional injection technique.

Following tonsillectomy, the epithelization of wound healing remains unknown. This process occurs via secondary intention, beginning after tissue injury, with interactions among various cells and signalling molecules that result in the secretion of cytokines and the induction of healing. To improve wound healing, many methods have been investigated, with most studies using PRP applied topically, but results are inconsistent. These discrepancies may be attributable to differences in PRP preparation and application protocols, the techniques employed for application, the evaluation methodologies, and the duration of postoperative monitoring [10, 14, 20]. In our study, we used PRP injection with a small needle directly into the tissue, which allows PRP to penetrate deeply and locally. We found that grade III epithelialization percentages were higher in the intervention group than in the control group, as mentioned above. An expanded sample size and extended follow‐up period could reveal statistically significant differences. The associated factors that may affect wound healing include intraoperative or postoperative bleeding, requiring surgeons to use electrocautery to stop bleeding, and inducing tonsillar beds and surrounding tissue to cause more injuries. Postoperative infection arrests the healing process due to bacterial growth. Two patients had postoperative bleeding, which worsened at the epithelialization stage.

Post‐tonsillectomy pain is multifactorial in origin and is caused by mucosal and muscle damage due to heat, pressure, and tear, followed by exposure of the glossopharyngeal and vagus nerves. Pain affects the return to normal eating and daily life. Although PRP is believed to modulate inflammation and enhance tissue repair, it did not demonstrate a significant difference compared with normal saline in reducing pain in our study, consistent with the results of Sidman et al. [16] for paediatric patients undergoing tonsillectomy.

Other studies, however, have suggested that PRP has benefits in reducing post‐tonsillectomy pain [10, 11, 12, 13, 14, 15, 16, 17]. The discrepancy may be attributed to multiple factors, such as differences in adjusted PRP volume, which may have achieved sufficient distribution in patients with larger tonsillar fossae; PRP leakage during administration; and methods used to assess wound healing. Future research would benefit from protocol standardization to address these variables. Another critical consideration is the lack of a standardized grading system to evaluate post‐tonsillectomy wound healing [2]. Establishing a uniform, validated tool for assessing wound healing would enable more reliable comparisons between interventions.

4.1. Limitations

This study was limited by its small sample size and short follow‐up duration, which may have compromised the study's capacity to detect meaningful differences in outcomes. Moreover, we conducted the power of study for testing two independent population proportions from n4Studies Plus, power testing is 0.885, with this result and the within‐subject design can ensure adequate power to detect clinically meaningful effects. To improve difference a larger, well‐designed, randomized controlled trial with a long follow‐up duration and a standardized wound healing grading system is necessary to clarify PRP's role in post‐tonsillectomy recovery.

5. Conclusion

In this randomized controlled trial, PRP injection into the tonsillar fossa during tonsillectomy was found to be safe and well tolerated, but it did not significantly improve wound epithelialization or reduce postoperative pain compared with normal saline. The differences in PRP preparation and application techniques and the absence of a proper wound‐healing measurement method contributed to variable outcomes. PRP remains a promising adjunct therapy, but additional studies are required to optimize PRP application, to more comprehensively assess PRP's effects on post‐tonsillectomy healing and recovery, and to determine whether specific patient populations or altered PRP protocols could provide improved results.

Author Contributions

Nilnetre Mahathanaruk: project administration, methodology, investigatiom, formal analysis, supervision, validation, writing – original draft preparation. Chattarin Jongkittipong: conceptualization, formal analysis, investigation, methodology, resources, writing – original draft preparation. Vipa Rath Marpukdee: conceptualization, project administration, methodology, resources, validation, supervision, writing – review and editing.

Funding

The authors have nothing to report.

Ethics Statement

This study was approved by the Human Research Ethics Committee of the hospital.

Consent

All patients provided written informed consent to participate in the study.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Data S1: coa70128‐sup‐0001‐CONSORTFlowDiagram.docx.

Data S2: coa70128‐sup‐0002‐CONSORT2025checklist30.03.2026.docx.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.