In 2017, Yael Bensoussan, MD, an otolaryngology fellow at the University of Southern California Keck School of Medicine in Los Angeles, attended a lecture on platelet-rich plasma (PRP) injections in the larynx. Dr. Bensoussan, who was in medical school in Canada at the time, noticed that PRP was used by oral-maxillofacial surgeons to optimize healing after dental implant surgery and in plastic surgery but was rarely used by otolaryngologists. To find out why, she co-led a survey of Canadian otolaryngologists and maxillofacial surgeons to learn if and how they used autologous platelet products.
Explore This IssueDecember 2020
“The results of our survey showed that only 14% of the OTO-HNS respondents were using PRP, compared to 30% of oral-maxillofacial surgeons. Interestingly, most otolaryngologists said they weren’t using it due to lack of information about the product,” she said.
Now, three years later, Dr. Bensoussan is starting to see more evidence in the otolaryngology literature that autologous platelet products can be effective in promoting healing for procedures such as tympanoplasties, facial rejuvenation, and hair transplantation, as well as myringoplasty. Most published, high-quality evidence on PRP in otolaryngology is from animal studies, with results showing that PRP increases growth factors to promote healing in scars up to 14 days after injection, she said.
To perform PRP therapy, surgeons must draw a patient’s blood and spin it in a centrifuge to extract the platelet-rich portion, which can take up to 30 minutes. The injected, enriched blood must contain 250,000 platelets per milliliter, according to current standards approved by the U.S. FDA. There are many different PRP kits and systems available, so the final concentration of platelets, as well as leukocytes and growth factors, may vary. “There’s more unknown about this biologic modality than there is known, including the ideal concentration of platelets and the frequency of treatment,” said Jeffrey Epstein, MD, a private practice otolaryngologist in Miami and New York City.
Another, newer autologous platelet product is platelet-rich fibrin (PRF). With PRF, the patient’s blood is spun in the centrifuge at a lower speed so that platelets aren’t stripped of their fibrin, and it has no anticoagulants, said Los Angeles facial-plastic surgeon Kian Karimi, MD, who is the medical director for CosmoFrance, a manufacturer of a PRF system. PRF forms a smooth gel that holds in place, while PRP remains liquid. “With PRF, there’s a slow release of growth factors over a longer period of time, almost like an extended-release capsule,” he said.
Alopecia patients at Massachusetts Eye and Ear are treated with PRP as either a less invasive, stand-alone therapy or in conjunction with hair transplant, with a recommended series of three injection treatments four to six weeks apart. “Hair loss can be devastating for patients. Multiple studies have shown that both men and women who are suffering from hair loss are negatively affected and, conversely, benefit greatly after treatment to restore their hair,” said Linda N. Lee, MD, who co-authored a systematic literature review on PRP’s efficacy and safety for alopecia patients in 2018 (Facial Plast Surg. 2018;34:631-640). “Anecdotally, PRP holds a lot of promise as a hair loss treatment. There are so many individual stories about unbelievable patient results with PRP. However, as an evidence-based field, we wanted to evaluate data objectively and understand what the risks and benefits truly were.”
The review by Dr. Lee and colleagues analyzed eight randomized controlled trials and 16 prospective cohort studies, and excluded case reports. They found that 21 of the studies reported positive outcomes based on objective clinical criteria, while three suggested no clinical improvement. However, in two of those three studies, patients reported increased satisfaction with their results. PRP also appears relatively safe, said Dr. Lee: The only complications were transient edema or erythema, and the pain and headaches associated with the procedure.
PRP can promote axon regeneration, where you actually regenerate nerve tissues to switch back on these disrupted neural connections. It may have an anti-inflammatory effect and upregulate growth factors to regenerate these nerves. —Zara M. Patel, MD
Dr. Epstein also currently uses PRP to treat alopecia. “We utilize PRP in the treatment of hair loss in several indications. PRP is performed at the same time as a hair transplant. When injected into the scalp prior to making recipient sites, we believe it reduces the ‘shock’ hair loss and accelerates healing,” he said. “PRP is also done as a stand-alone therapy for the treatment of androgenic alopecia.” Dr. Epstein recommended that alopecia patients have repeat injections two months after the initial treatment, then every four to six months afterward.
Currently, Dr. Lee’s clinic uses PRP only for alopecia treatment, but she believes that PRP may also promote wound healing in patients with tympanic membrane perforations or after facial aesthetic surgeries. “Because of its possible benefits across multiple different indications, PRP has sometimes been referred to as ‘liquid gold,’ but it’s important that as physicians we carefully select the right candidates and accurately inform our patients of the evidence and realistic risks.”
Dr. Karimi believes that adding PRP or PRF injections increases success rates for fat transfer procedures, where fat is taken from the patient’s abdomen and applied to the face for either cosmetic or reconstructive treatment. “We’re using that patient’s own fat cells, or a fat graft, and you need the fat to perform well in its new environment. This hasn’t worked so well in the past,” he said. “When you add PRP or PRF, the take rates of fat can approach 50% to 70% of the volume injected. Patients see better results, and there are improved take rates for the fat.”
PRF is also helpful in rhinoplasty because it increases the blood supply to the grafts, added Dr. Karimi. “The platelets are the first cells to come to a wound to promote healing. They create a spider’s web of fibrin, and spin and signal growth factors to the wound,” he explained. “In rhinoplasty, most of the time we use cartilage grafts that have no inherent blood supply—they rely on the surrounding tissue. PRF is helpful in rhinoplasty because you want something to restore the blood supply and promote wound healing.”
Safety and Evidence Concerns
According to recent evidence, PRP therapy could improve wound healing and outcomes in cosmetic or reconstructive procedures. But otolaryngologic surgeons say safety concerns and a lack of research-based evidence remain hurdles to overcome before adopting it into wider use for their patients.
Rhinologist Zara M. Patel, MD, director of endoscopic skull base surgery at Stanford University School of Medicine in Stanford, Calif., has used PRP only in research settings because of the lack of robust evidence. “As a physician, I want more data so that I can be sure that any therapy is effective and worthwhile to use in a clinical setting,” she said. “PRP isn’t covered by insurance because it isn’t yet proven as effective in olfactory loss or other conditions.” (See the sidebar “Out of Pocket Costs,” below.)
Because PRP is an autologous blood product, some surgeons stress its safety, but questions remain, said Dr. Patel. She specifically wants more data on whether PRP, which upregulates various growth factors to stimulate stem cells and promote new tissue generation (Blood Res. 2016;51:3-5), could trigger tumors if injected into the nasal cavity, but noted that its other benefits look promising. “PRP can promote axon regeneration, where you actually regenerate nerve tissues to switch back on these disrupted neural connections,” she said. “It may have an anti-inflammatory effect and upregulate growth factors to regenerate these nerves.”
In addition, Dr. Epstein has a concern regarding its use in patients infected with the novel coronavirus. Hematology researchers recently published a study that shows that increased platelet activation is associated with poor outcomes in severe COVID-19 patients, and that hypercoagulability could result in thrombosis and death (Blood. 2020;136:1330-1341). Because COVID-19 is such a new infection, however, the pathophysiology behind hypercoagulability in patients isn’t well understood. “At this point, I’m recommending against PRP in patients who have had COVID-19 because of the risk of inducing a hypercoagulable state,” he said.
Research in PRP use in otolaryngology has been slow to develop, but it is becoming easier to find. A decade ago, Dr. Karimi attended a lecture on topical application of PRP after ablative laser procedures. “The speaker found that his patients had a lot of pain and needed a lot of time for healing. Anecdotally, they saw less pain and improvements in healing time with PRP,” he said. He reviewed literature on PRP at the time and found mostly opinion papers and non-randomized trials. “Now, there is more evidence on PRP use in otolaryngology and facial-plastic surgery. The strongest evidence on its use is in wound healing.”
Recent studies on PRP in otolaryngologic surgery are mostly small but show benefits:
- In a 2015 literature review of 47 studies of PRP, leukocyte-rich PRP and PRF in facial rejuvenation surgery, patient recovery, and wound healing after facial plastic surgery, results showed significant, measurable effects on cellular changes, wound healing, and aesthetic outcomes of these surgeries, including enhanced fat graft survival (Aesth Plast Surg. 2015;39:495-505).
- In a 2016 prospective study from the United Arab Emirates, 38 patients who had open rhinoplasties with osteotomies (19 PRP, 19 controls) were followed for 90 days. In the PRP group, surgeons injected 1 ml of PRP under each eye and 2.5 ml into the subperichondrial septum, on the dorsum of the nose, at the sites of osteotomies, and at the columella around the open rhinoplasty wound. There was significant improvement in periorbital and nasal edema and less postoperative bleeding in the PRP group, but no significant differences between groups in postoperative bruising. PRP group patients were able to remove their nasal packing earlier due to less bleeding and edema (Otolaryngol (Sunnyvale). 2016;6:280).
- A 2019 study from Japan evaluated 118 patients who had minimally invasive myringoplasty and surgical closure of chronic tympanic membrane perforations. Surgeons inserted an atelocollagen sponge injected with PRP into the perforations. They found that 98.5% of patients with small perforations, 80% with medium perforations, and 85.7% with large perforations achieved closure, although some required multiple surgeries. The study concluded that PRP was safe, satisfactory, and promising for promoting wound healing in office-based procedures (Auris Nasus Larynx. 2020;47(2):191-1970).
- In February 2020, Dr. Patel co-authored a small, single-arm pilot safety study on one PRP injection into the nasal cavities of seven patients with olfactory dysfunction (Laryngoscope Investig Otolaryngol. 2020;5:187-193). Results showed that PRP was safe, and patients all noted some improvements in smell threshold, but benefits didn’t continue.
The results from Dr. Patel’s study were encouraging enough, however, to prompt a new clinical trial, which will recruit patients soon. (ClinicalTrials.gov Identifier NCT04406584). Patients will be randomized to receive either three 1 ml PRP or saline injections into the olfactory cleft every two weeks to see if a series of injections will trigger more sustained improvement. “We need to find more globally effective therapies to help the other 50% of patients who don’t respond to steroids or other treatments,” said Dr. Patel. “Their condition is very impactful on their quality of life. For some, their sense of smell never comes back.”
Dr. Bensoussan is working on a new trial led by Michael Johns, MD, and Karla O’Dell, MD, to test the effects of PRP injections into vocal fold scars (ClinicalTrials.gov Identifier NCT03749863). Surgical removal of these scars often worsens the condition, and the current standard of care is steroid injection.
“PRP is a promising approach. The goal is to soften the scar tissue to achieve better vibration of vocal cords and optimize the voice,” and PRP could represent an easy, low-risk alternative to current treatments, Dr. Bensoussan said. “For patients who use their voices every day, a vocal fold scar can cause strain and fatigue and have a significant impact on quality of life.”
Susan Bernstein is a freelance medical writer based in Georgia.