A review on Hair Regrowth with platelet rich plasma-Hair Regrowth




Abstract Plaquelet rich plasma (PRP) is described as a small amount of plasma with higher levels of platelets than those in peripheral blood. It was originally utilized as a transfusion drug to treat thrombocytopenia. It has been discovered that there are a variety of cell-growth factors as well as cytokines which could speed up wound healing and tissue regeneration, which leads to a broader range of uses in healthcare, including in sports medical, regenerative medicine as well as aesthetic medical. A number of studies have proven that PRP is a viable option efficiently to treat hair loss. While it is extensively used, the precise mechanism of PRP’s actions is not completely understood. The purpose of this paper is to hope to summarize and revise current information regarding its definition, classification, the mechanism of action, clinical efficacy hair regrowthand other negative effects of PRP.

 

The plasma rich in platelets (PRP) is identified as a treatment for thrombocytopenia in Hematology as a tiny amount of plasma with higher concentrations of platelets than those in peripheral blood. It was initially used as a transfusion agent for the treatment of thrombocytopenia from 1970. Today, PRP is the most sought-after treatment for numerous ailments in sports treatment, medicine for regenerative purposes cosmetic medicine 4, as well as hair loss treatment because it is a source of a wide range in cytokines and growth factors which will speed up healing from wounds and restore tissue. The instrument used to separate platelets as well as the subsequent use of the product are regulated by the by the US Food and Drug Administration (FDA). Any other use of PRP than blood transfusions is considered an “off label usage” that isn’t prohibited by FDA regulations if it is carried out by a physician who has the intention to practice medical practice. However, despite its wide-spread use however, the mechanism behind the effects of hair growth induced by PRP has not been completely studied. We will review the efficacy of PRP as an option for treating hair loss and loss of hair, including definition, classification mechanism of effect, clinical efficacy, hair growth, as well as negative effects.

Definition

Platelet-rich plasma, also referred to as growth factors with a high level of platelets (or platelet concentrate), is the concentration of plasma proteins rich in platelets that are taken from whole blood and centrifuged to eliminate Red blood cell debris. Apart from the principal component which has high levels of platelets, there’s other components, including whether or not leucocytes are present, and platelet-activating agents. These are serve to determine different kinds of PRP. The efficacy of stimulating tissue regeneration is dependent on the amount of platelets in the plasma. Numerous studies have revealed that concentrations of two to six times greater than the normal platelet count are required to ensure optimal outcomes.

Preparation

In the absence of any standard procedure for preparation and use of PRP it is possible to use a selection of techniques for its preparation. The idea is to make concentrated platelets using the blood of the patient. The PRP preparation procedures follow the same general procedure, beginning by obtaining venous blood of 10 to 60 milliliters from the patient before putting it in tubes that contain an anticoagulant such as acid citrate dextrose solution or sodium citrate to prevent coagulation as well as premature release of the alpha granules. After that, the whole blood is centrifuged, and then divided into three layers according to particular gravity. The lower layer is composed of the red blood cell (RBCs) with leukocytes , the middle layer is PRP and that on top is platelet-poor Plasma (PPP). 9 There are many kinds that are available commercially which simplify the preparation of PRP. The kits vary in the concentration of platelets, as well as and the amount of leukocytes as well as platelet activator , which results in the different growth factors ‘ concentrations. This explains the different positive clinical effects of PRP that have been that are reported in the research literature. Certain studies stimulated growth factor release and the degradation of alpha granules using calcium gluconate, calcium chloride or thrombin prior to the administration (activated PRP). There isn’t a consensus on whether platelets need to be activated externally or rely on host thrombin as an activated endogenously to maximize the therapeutic effects. The alpha granules of platelets release hormones that stimulate growth within 10 minutes after clotting activation. Therefore, PRP should be administered within 10 minutes after activation to reap the greatest benefit.

Classification of Platelet Rich Plasma

There are numerous variations in PRP preparations depending on the collection tubes to the amount of power as well as how many cycles used, the time of centrifugation components of PRP, and the activation procedure was employed. A uniform classification of PRP is known as DEPA was suggested by Magalon and colleagues using four elements that include dose of the platelets injected (baseline level of platelets of 200×10 9/L) as well as the effectiveness of the procedure (platelet recovery rate in %) as well as the high purity of PRP (relative composition of platelets percent) and activation procedure. According to this classification it is clear that an “AAA” DEPA score is refers to a high-concentration platelet injection (>5 billion) with low red blood cell contamination and properly prepared using the correct method that results in a minimal loss of platelets from the whole blood. The final category of the DEPA classification is whether or not there is any external activator like thrombin, and calcium chloride.

 

Action Mechanism of Action

Numerous studies have shown that platelets do not only impact the hemostatic system, but also influence the angiogenesis, inflammation and stem cell stimulation and cell growth through the release of various cell-growth factors as well as cytokines. Platelets that are activated in PRP release various cells and growth factor out of their alpha granules. This includes the platelet-derived growth factor (PDGF) as well as the transforming growth factor b (TGF-b) and fibrillary growth factor-2 (FGF-2) and vascular epidermal growth factor (VEGF) epidermal growth factors (EGF) and insulin-like-growth factor-1 (IGF-1) and the neurotrophic glial cell line (GDNF) and GDNF, all of which have a significant role to play for stimulating growth of hair by stimulating cell proliferation, differentiation , and angiogenesis. GDNF is able to stimulate cell proliferation and shield hair follicles from catagen-induced transition. The VEGF plays a significant function as a potent stimulator of hair growth through Angiogenesis-inducing. IGF-1 is a stimulator of the proliferation of the cyclical Ki67 and basal keratinocytes. It also helps to trigger and extend the anagen stage of the cycle of hair growth. Furthermore, PRP may stimulate the growth of dermal-papilla (DP) cells through activation of Extracellular Signal-Related Kinase (ERK) and the fibroblast growth factor 7 (FGF-7) beta-catenin as well as Akt activation (an anti-apoptotic signaling protein). Also, there is an increase in the expression of the Bcl-2 proteins (an anti-apoptotic element) in the human dermal papilla cell that have been cultured using PRP. This clearly demonstrated that PRP may enhance the life span of hair follicle cell lines through anti-apoptotic actions and also increase hair growth by prolonging the phase that is known as the “anagen” of hair growth. This hypothesis was further supported by results from microscopic analysis that showed an increase in the number of follicular bulge cell, epidermal thickening and vascularization and a greater number of Ki67 + basal keratinocytes within the scalp tissues treated with PRP compared to placebo.

Contraindication

Although PRP is considered to be a safe treatment with no adverse side consequences, there are some limitations that should be taken into consideration. A complete contraindication to PRP is critical platelet dysfunction, thrombocytopenia bleeding disorders, sepsis locally-infected (site PRP) and patients who are unwilling to take the risk. Contraindications to NSAIDs are: use within 24 hours, glucocorticoid infusion at the treatment site within a month or systemic glucocorticoid in less than two weeks and fever or illness that has recently occurred and cancer of the bone, especially hemotolymphoid anemia (hemoglobin less than 10 grams per deciliter) or the thrombocytopenia (platelets smaller than 150,000 per microliter) and smoking cigarettes.

 

Utilization of Plasma Rich Platelets for Hair Disorders

Androgenetic Alopecia

androgenetic alopecia (AGA) is an alopecia without scars that is characterised by a shorter anagen phase, and a gradual diminution of terminal hairs into hairs called vellus. 33 AGA is seen in around 50 percent of Caucasian males by at the age 50 and for women, it could be at least 50 percent throughout their life. For males, baldness starts by a frontal recession, and then thinning of the vertex area (MPHL) and in women, loss of hair is characterised by lower hair density and a smaller shaft diameters over the crown, without frontal recessions of the hairline (FPHL). FDA is approving oral finasteride (for males exclusively) in addition to topical minoxidil as a treatment of AGA.

A meta-analysis of the six research investigations (four studies were controlled, randomized trials and the two others included retrospective research) that included 177 patients found a significant increase in the number of hairs per centimeter 2 after PRP injections , compared to the control group (mean differencia (MD) 17.90 95% confidence interval (CI) 5.84-29.95, P=0.004) and the tendency to increase in the number of hairs as well as in the proportion of hairs that are thick. Similar results were verified by two more meta-analysis studies, which revealed significant increase in hair counts per centimeter 2 after PRP injections the treatment group as compared to the control group. The results were MD 38.75 95 percent C.I. 22.22-55.28 (P) <0.00001 in addition to MD 30.35 and 95 percent 95% CI 1.77-58.93 P <0.00001 and MD 30.35, respectively. Comparatively to minoxidil, finasteride and adult stem cells-based therapy, 84% in all studies found positive effects of PRP. 50% of the studies showed an statistically significant improvement, and 34% of the studies showed hair density and thickness growth, but there was no statistical or P value analysis was reported.

While several clinical trials demonstrated the efficacy of PRP treatment for AGA, there isn’t any routine procedure in PRP treatment and preparation and an approach to measure the results. There have been attempts to standardize the PRP treatment procedure to AGA patients. A standard procedure for PRP was developed in the work of Stevens et al, employing the single spin centrifugation technique to generate pure PRP. the enrichment of platelets of three to six times that of the average concentration of the whole blood, and incorporating an activator for platelets like calcium gluconate or calcium chloride prior to administration of PRP in subdermal injections. The treatment intervals should consist of every month for the initial 3 months, and then each 3 months during beginning of the year.

However, there’s a controversy in the literature regarding the standards of PRP preparation. A prospective split-scalp comparative study that involved 15 females with AGA . It was conducted by intradermal injections of double-spin-prepared PRP into the right side of the scalp. Single-spin prepared PRP in the left portion on the scalps of all patients for 3 sessions of treatment, spaced 3 weeks between each. Results showed improvement on both sides of scalp. Hair density was measured by trichoscan demonstrated that the right-hand side on the scalp had greater in the median density of hair than the left-hand half (P equals 0.031) this demonstrated that the double-spin procedure could produce superior results over single-spin. Furthermore, research that demonstrated that patients who received non-activated PRP were shown to have higher increases in hair count as well as hair density total (31 percent + 2 in comparison to 19% + 33%, P= 0.0029) as compared to patients treated with activated PRP, leading into the belief that the PRP doesn’t require activation prior to injection.

The main factor that influences the efficacy of PRP is the amount of platelets. Platelets with higher numbers are more effective than smaller numbers of platelets in regards to the density of hair, diameter and the density of hair at the terminal. 41 In AGA, the action of dihydrotestosterone upon dermal papilla cells slowed down WNT canonical signaling, resulting in hair growth that was not as healthy and slowing the process of hair growth. PRP is a hair-growing hormone that works through activating the signaling of WNT and b-Catenin leads to the proliferation and differentiation of hair follicles and also triggers the start of a new cycle of hair.

A few studies have demonstrated the ineffectiveness of PRP during AGA treatment. This may result from the low concentration of platelets, the small quantity of PRP injection, and insufficient quantity of therapy. 9 The effect of treatment PRP treatment in AGA patients can be determined by analyzing pro-inflammatory cytokine INF-1a genotype in peripheral blood. A study has revealed that there is a significantly higher prevalence of the C/C genotypes of IL-1a in patients who respond (66 percent) as compared to non-responder patients (22 percent) having odds ratio (OR) 6.68 (95 percent of the interval 0.99-72.95 (p<0.05).

 

Male Pattern Hair Loss

Female-pattern hair loss (FPHL) is the main prevalent reason for hair loss in middle-aged women. It is which is characterized by progressive miniaturization of follicular follicles and the transformation of terminal follicles to vellus-like follicles. This results in an increase in the density of hair loss, hair loss and diffuse alopecia without scarring, particularly in the frontal, central and parietal areas on the scalp. The reason for this issue is unclear, but it may be due to hormonal imbalances, genetics and environmental factors.

A systematic review study that evaluated the efficacy of PRP for treating FPHL consisting of 92 patients from 6 controlled clinical trials that were randomized found that PRP had an impact on FPHL treatment, by increasing hair’s thickness and density. Recently two meta-analysis studies have proven the efficacy of FPHL treatment using PRP. The first study comprised 776 females who participated in 16 controlled studies randomized to control and 26 observational studies, showed that PRP had beneficial effects on FPHL in terms of hair density, as compared to the control group with an OR 1.61 with 95 percent of CI 0.52-2.70 as well as in comparison to baseline which had an OR 1.11 with 95 percent of the time 0.86-1.37. The second study , which included 8 clinical studies, and 777 subjects demonstrated an increase in the number of hairs and hair diameter in four studies following PRP treatment. Furthermore, PRP has been demonstrated to bring about the highest levels of satisfaction as well as an improvement in quality of life for patients suffering from FPHL.

The treatment effectiveness of PRP is different for AGA by PRP in women and men was found in a meta-analysis research study which showed that PRP increased volumetric hair (N of 250; MD equals 25.83, 95 percent confidence interval: 15.48-36.17, P < 0.00001) and hair diameter (N = 123, MD = 6.66, 95 percent 95% CI: 2.37-10.95 (P = 0.002) for men, while significantly increasing the diameter of hair (N 95; MD = 31.22, 95 percent CI: 7.52-54.91 (P = 0.01) however, it did not improve hair density (N > 92 MD = 43.54, 95 percent CI: -1.35-88.43 P = 0.06) for women. But, the extent to which PRP’s effectiveness in treating AGA is affected by gender. The issue is unresolved due to the differing results of the various studies listed. Many of the studies analyzed were not randomized, controlled, and contained a small sample sizes.

 

Alopecia Areata

Alopecia areata (AA) is a widespread autoimmune disorder that causes non-scarring Alopecia in females and males regardless of age. The lifetime risk of AA is about 2 percent of the population there is no distinction in frequency between genders. Most patients experience only one alopecia-related lesion and hair growth that occurs spontaneously could occur in a matter of months or years. But, there are a number of people who develop multiple lesions that become permanent loss of hair.

PRP was found to possess an anti-inflammatory and potent effect. It inhibits the release of cytokine inflammatory mediators and reduces inflammation of local tissues and can be useful in the treatment of inflammatory hair loss like AA. PRP was first tested in patients suffering from AA through an randomized, double-blind half-head study that was placebo controlled. 45 patients suffering from AA were randomly assigned to get intralesional shots with PRP or triamcinolone acetonide , or placebo, on one side of their scalps, while the remaining half was left untreated. The results indicated the fact that PRP dramatically increased hair growth and Ki-67 levels (marker for the proliferation of cells) in comparison to triamcinolone Acetonide as well as placebo. A number of controlled studies that were randomized showed that PRP treatment can boost hair regrowth to the same degree as the intralesional injection of triamcinolone acetonide for the treatment of AA. Two recent studies have compared the therapeutic effects of intralesional injections of PRP versus triamcinolone-acetonide treatment in AA. One study showed that the end-to-end severity of alopecia instrument (SALT) score had significantly lower levels in both groups , compared to the baseline level (P equals 0.025 as well as the P value was 0.008) but there was no significant differences between the two treatment options in terms of clinical improvement. Likewise, the the final alopecia areata symptom-impact scale (AASIS) had a significant reduction in the PRP groups (P equals 0.006) however not in the the triamcinolone group (P > 0.062). Similar results were also observed in the second study finding that there was not a significance in the statistical difference of the SALT score reduction or hair regrowth scale between the two groups.

However the opposite was observed in three controlled, randomized clinical trials that showed that PRP was less effective than intralesional injections of steroid basing on Mac Donald Hull and Norris grade systems, percent of hair growth and decrease in SALT score from baseline respectively. These results can be explained by the fact the fact that steroid is more powerful than PRP in terms being immunosuppressive and exerting a powerful inhibition of the activation of T lymphocytes.

The beneficial effects of combining therapy using PRP was demonstrated in a patient suffering from long-standing AA treated by an intralesional injection of triamcinolone acetonide as well as PRP on one side of the scalp, while the other portion of the head was treated using intralesional triamcinolone Acetonide alone. The scalp treated using the combination therapy showed greater hair growth and a larger hair fiber in diameter. In addition, an investigation that looked at the effectiveness of PRP treatments in 20 patients with chronic AA that had not responded to conventional treatment for 2 years. The study showed that all patients suffering from chronic AA were treated successfully using PRP. However, only one patient experienced an relapse within one year of following-up. The successful treatment with PRP was also reported in a patient with corticosteroid-resistant ophiasis AA who experienced hair regrowth after PRP injections and a patient who suffering from alopecia areata barbae. Thus, PRP can be utilized as an alternative therapy for patients who aren’t responding to conventional treatment or those who do not desire treatment with steroids . It can also be utilized as an adjuvant therapy to treat alopecia areata.

Cicatricial Alopecia

Cicatricial Alopecia is a form of alopecia scarring, which is due to various injuries, inflammatory conditions burning, serious infections that cause the destruction of hair follicles and scarring. The aim of treatment is stopping the progress of the disease and avoid further loss of hair and scarring, by using various anti-inflammatory medications, including intralesional triamcinolone or topical steroids, injections or immunomodulating medications. But, there is no cure that is effective to promote hair growth in the fibrotic area.

Frontal fibrosing and alopecia (FFA) is an alopecia variant of lichen planopilaris, the most frequent form of cicatricial hair loss, which is characterised by the progressive recession of the temporoparietal and frontal hairline as well as perifollicular hair papules and erythema that can lead to scarring in the form of a band in the frontotemporal zone. 74 The positive treatment result by five consecutive injections of PRP was observed in a 44-year-old female suffering from FFA with an unresponsive history to standard intralesional steroid therapy. Within a month of treatment, the perifollicular erythema papules of lichenoid, as well as scaling on the frontotemporal line of hair were reduced, and no more hair loss was observed within 5 months.

The Lichen Planopilaris (LPP) is an alopecia that has a chronic, inflammatory scarring that is characterized by follicular hyperkeratosis perifollicular erythema and the disappearance of follicular pores on the parietal and vertex areas in the hair. Bolanca et al have reported for the first time the effectiveness of PRP treatment in a case of LPP identified by histopathology, and not responsive to previous treatments. After three consecutive treatments of PRP and follow-up for 6 months, the patients were able to completely reduce hair loss and scalp itching as confirmed by the absence of perifollicular erythema as well as scaling on the trichoscopic exam. In the following months, two patients suffering from central centrifugal cervical alopecia (CCCA) as well as one suffering from LPP were described as having a positive outcome from PRP treatment, which resulted in an growth in hair volume despite their inability to respond to conventional treatment prior to.

Effective treatment of cicatricial and alopecia through PRP is possible because of a variety of cytokines and growth factors like TGFb, TGFb1 in platelet granules. These have anti-inflammatory and proangiogenic properties. There is evidence to suggest that PRP may be utilized as a treatment effective for certain types of cicatricial alopecia More clinical trials are required to establish further evidence.

Hair Transplantation

Numerous studies have proven an effective effect of PRP when combined and hair transplantation. The first study was an experiment in 20 patients with male pattern hair loss that showed an increase of 15% in hair growth rate in the follicular unit density of areas that were treated prior to harvesting the donor with growth factors of platelet plasma taken from the patient’s autologous plasma, compared to normal saline (18.7 follicular units/cm 2 and 16.4 follicular units for each cm 2.). Similar results were also observed in two additional studies. The first was a comparative study which showed that follicular unit transplants when combined with platelet lysate (PL) as well as activated PRP (AA-PRP) recover quicker than normal saline four months following the operation with 99%, 75 71%, and 99 percent of follicle growth had been observed in the PL, the AA-PRP and the areas of saline treatment as well, according to. Another randomized controlled study that showed that the preservation of hair grafts in PRP prior to implanting increases hair’s density, growth rate of the grafts, as well as the thickness of hair compared to the preservation the grafts in normal Saline. 81

In addition, PRP may be utilized as a treatment in conjunction with Follicular Unit Extract (FUE) hair-transplantation procedure process as illustrated in a single-blind prospective, randomized study of forty FUE hair transplants patients. Patients were split into two groups. PRP was administered intra-operatively after the insertion of slits on the area of recipient in the PRP group, whereas normal saline was injected into non-PRP groups. It was evident how intra-operative PRP treatment can be beneficial in providing significantly improved quality and density of hair growth, while reducing the loss of catagens from transplanted hair, accelerating the recovery of the skin and quicker growth of new hair in patients who have FUE transplants. Therefore, PRP isn’t only a successful therapy for hair loss, is also a viable option in conjunction with hair transplantation.

Affects Negatives on Platelet Rich Plasma

The PRP procedure is an autologous process of plasma, which has a significant amount of platelets. It is an extremely safe treatment with no adverse side effects, such as a temporary and manageable discomfort during treatment, mild headache, minimal itching occasional edema and erythema that appears on the treated areas. None of the major side consequences such as wounds, infections and panniculitis. Hematoma, scarring, or allergic reaction have been observed after PRP treatment. Following treatment, patients are able to return to their normal routines, no antibiotics are required to treat the spread of infection. The majority of patients are able to resume work the following day.

Conclusion

PRP can be utilized as an innovative therapeutic option to treat hair loss such as androgenetic androgenetic or female pattern loss of hair or as an individual therapy or as an adjuvant treatment to conventional therapy and hair transplantation. PRP is also thought to be an effective, safe, steroid sparing alternative treatment for Alopecia areata. Furthermore, there was evidence to suggest that PRP may ameliorate symptoms of some forms of cicatricial hair loss. However, more research is required to determine the best method of PRP treatment preparationand treatment regimen, which includes dosage protocols, injection techniques and frequency of the most effective treatment sessions to ensure most effective therapeutic effectiveness.

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