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Research in Review

Incorporating Platelet-Rich Plasma for Hair Restoration Into Your Practice

March 2017

Hair loss affects both men and women and can have a significant impact on quality of life, both personally and professionally. The most common type of hair loss is androgenic alopecia (AGA). It affects up to 50% of white individuals by age 50 and nearly 50% of women over the course of their lifetime.1,2 AGA is progressive, leading to a decrease in the density and diameter of the hair, miniaturization of the hair follicle, and potentially significant baldness. Men and women experiencing balding report a lack of self-esteem and confidence. The lack of confidence and increasing embarrassment often affects their interpersonal relationships and even their professional growth.3

Although men and women are both affected by their hair loss, there are many differences, including presentation, prevalence, and pathophysiology.

Male Pattern Hair Loss
AGA accounts for 95% of the hair loss in men. Male pattern hair loss (MPHL) is caused by an underlying genetic factor that makes the hair follicle sensitive to dihydrotestosterone (DHT). This will cause progressive thinning of the hair and miniaturization of the hair follicle leading to the inability to grow thick, full hair. When considering treatment, it is important to understand how far the hair loss has progressed and this can be done by using the Norwood Scale and a densitometry.3 Male pattern baldness is typically characterized by a receding hairline at the temples and thinning at the scalp vertex, but differing patterns exist.

Treatment options for MPHL include minoxidil 5%, finasteride, ketoconazole 2% shampoo, low-level laser (light) therapy (LLLT),4 surgical hair restoration, nonsurgical hair restoration with platelet-rich plasma (PRP), PRP and ACell, microneedling (pen or roller), topical hair products (ie, Qilib or Revivogen), oral supplements (ie, Viviscal or Nutrafol), and topical growth factors.

Female Pattern Hair Loss
The prevalence of female pattern hair loss (FPHL) appears to advance with age and menopause. Twelve percent of women first develop clinically detectable FPHL by age 29 years, 25% by age 49 years, 41% by 69 years, and more than 50% have some element of FPHL by 79 years of age.5 As women approach menopause, their estrogen levels decline and levels of androgens can increase causing a relative increase in DHT. Lab results may not reflect abnormal androgen levels; therefore, the health  care provider does not relate the hair loss to an overproduction of androgens. These women—just like men—have a genetic propensity for follicular miniaturization. Because women present differently on clinical exam, it is important to use the Ludwig, Savin, or Olsen Scale to determine the progression of hair loss.5

Presentation may include a thinning and widening of the midline part with minimal disruption to the frontal and temporal regions. Women can also present with diffuse thinning, which makes it more difficult to diagnose.5 Therefore, it is necessary to rule out underlying androgen-secreting tumors, endocrine disorders, medication-induced alopecia, telogen effluvium, alopecia areata, as well as inflammatory and autoimmune disorders.3 Women often have multifactorial causes related to hair loss.

The recommended diagnostic tests for women include hormone levels (dehydroepiandrosterone, total testosterone, androstenedione, prolactin, follicle-stimulating hormone, and luteinizing hormone); comprehensive metabolic panel; zinc; Lyme disease screen; serum iron; serum ferritin; total iron binding capacity; thyroid-stimulating hormone (T3, T4,); VDRL test (a screening test for syphilis); complete blood count; scalp biopsy; hair pull; and densitometry.3

Minoxidil (2% and 5%) is the only FDA-approved medication for women. Other treatment options for women include aldactone/spironolactone; estrogen/progesterone; oral contraceptives (caution in women older than 35 years); ketoconazole 2% shampoo; finasteride (contraindicated in women of childbearing age); LLLT;4 surgical hair restoration; nonsurgical hair restoration with PRP; PRP and ACell; microneedling (pen or roller); topical hair products (ie, Qilib or Revivogen); oral supplements (ie, Viviscal or Nutrafol); and topical growth factors.

Platelet-Rich Plasma
PRP is a method for the treatment of AGA that has shown positive results.6-12 (See Figures 1A-C and Figures 2A-B.) PRP is not FDA approved for the use in hair restoration, but certain PRP systems are FDA cleared. PRP is defined as an autologous high concentration of platelets in a small volume of plasma measured as 1,000,000 platelets per microliter of blood or at least 2 times the native concentration of whole blood.6,13

PRP contains platelets that are key to stimulating hair follicles to generate hair growth. The platelets in PRP become activated when injected into the scalp, releasing a variety of growth factors that bind in the bulge of the hair follicle, promoting hair growth.6,9,14 The platelets, when used to regenerate hair growth within follicles, promote healing and the formation of new cell growth. In addition, the platelets accelerate the rate and degree of regeneration so that you can expect to see telogen hairs cycle to anagen in a timely manner. There is also a prolonging of the anagen phase. This is a component of hair restoration because it is effective in stimulating inactive hair follicles, causing them to revert to the growth phase.6,14

Growth factors within PRP that assist in the process of natural hair restoration include11,13,14:

• Platelet-derived growth factor—promotes blood vessel growth, cell replication, skin formation
• Transforming growth factor-b—promotes growth of matrix between cells, bone metabolism
• Vascular endothelial growth factor—promotes blood vessel formation
• Epidermal growth factor—promotes cell growth and differentiation, blood vessel formation, collagen formation
• Fibroblast growth factor-2—promotes growth of specialized cells and blood vessel formation
• Insulinlike growth factor—a regulator of normal physiology in nearly every type of cell in the body

When PRP was first used in nonsurgical hair restoration, it was time-consuming, uncomfortable to the patient, and less cost-effective than current methods. With the introduction of a new technique using subdermal depo bolus injections, hair restoration with PRP is less painful, less traumatic than intradermal injections, and is overall a more efficient injection technique. Subdermal depo bolus administration allows for diffusion of the PRP resulting in fewer injections.14

Starting PRP Therapy for AGA
First and foremost, ensure that you have diagnosed the patient correctly and categorize the type of hair loss your patient is experiencing (Tables 1 and 2).3

Next, make sure you have the proper supplies and medical staff who are proficient in phlebotomy (Table 3). Specimen handling is critical for proper outcomes. Proper labeling and identification is critical at each step. Do not invert the test tube once removed from centrifuge. Keep upright so the less concentrated

PRP can be drawn off and the 5 times concentrated PRP is left in the test tube. The highly concentrated PRP is key to the success of hair restoration.

The injection protocol includes:

1.    Draw blood into appropriate size PRP tube (22 mL)
2.    Invert several times mixing the anticoagulant into the blood
3.    Centrifuge for 10 minutes (See centrifuge instructions for speed recommendation)
4.    Draw off 6 ccs of platelet-poor plasma using a 10-cc syringe and rigid 50-mm needle, leaving behind 5 to 6 cc of PRP
5.    Optional—Add 0.1 mL lidocaine to new 10-mL syringe
6.    Invert tube 7 to 10 times, mixing the platelets with remaining plasma
7.    Draw up PRP using 10-cc syringe and Vacutainer Transfer Device
8.    Lie patient down and have them identify their blood
9.    Apply chiller to point of care
10.    Use 27g ½-in needle and inject approximately 0.3 to 0.5 mL PRP subdermally across areas of hair loss
11.    Treat once per month for first 3 to 4 months followed by maintenance treatment every 4 to 6 months

The key to this technique is ensuring you are injecting into the subdermal space, which will allow the PRP to enter this space with ease and with minimal discomfort to the patient.

Other Considerations
Setting expectations is another important factor to success. Like any procedure, results can vary between individuals. PRP does not work for everyone; the longer the hair has been dormant the less it responds. But in many instances, patients start to see results within 60 days of the first injection session.

Women in particular may take much longer before seeing results. Because AGA is a chronic, progressive genetic disorder, maintenance with PRP is a necessity for long-term success.

It is recommended patients have a treatment every 3 to 4 weeks for the first 4 months. At this point, they will enter into the maintenance phase. The patient should return every 6 months for PRP treatment. Limiting factors for treatment maintenance may be cost and time.

The cost of PRP ranges from $600 to $900 per treatment. Creating a package for the patient to include the first year of maintenance sessions will increase compliance through the maintenance phase. As such, PRP for hair restoration can significantly increase the revenue of your practice.

Other considerations include safety, contraindications, and complications. PRP is immunologically neutral and poses no danger of allergy, hypersensitivity, or foreign-body reactions. Sterile technique must be used at every stage of PRP preparation and application to reduce the risk of infection, which is not commonly seen. If administered by intradermal injection, a brief period of inflammation at the wound site may be experienced. Subdermal injection is advised. Nerve trauma and hematoma are other potential complications.1

Contraindication for use of PRP include critical thrombocytopenia (low platelet count); hypofibrinogenemia, hemodynamic instability (collapse); infection (sepsis); acute and chronic infections; chronic liver disease; anticoagulation therapy (warfarin, dabigatran, heparin); and scarring alopecia.13

Combination Treatments
Physicians who perform hair restoration often use PRP in combination with ACell, a non-cross-linked, completely resorbable, acellular extracellular matrix that also is used in wound healing. The protein in ACell is developed and manufactured from pig’s bladder.15 Therefore, it should be avoided in those with an allergy to porcine material and patients could possibly have a foreignbody reaction to the material. Some practitioners believe that this combination of PRP with ACell will prolong the effects of PRP and improve results.15

Microneedling is also commonly used in the treatment of hair loss and is an adjunct to PRP which is thought to prolong the effects of PRP and improve results.8 Microneedling can be done at the time of treatment or at home with a microneedling roller. When recommending a roller, it is advised to stay at a depth of 0.25 mm, which is the FDA-approved depth for microneedling rollers. Advise your patients to avoid purchasing rollers online that are at a greater depth of 0.25 mm.16

Conclusion
PRP is making advances in hair restoration, but is still in its early stages. An increasing need for more peer-reviewed studies exists to evaluate the efficacy and safety of PRP, PRP protocols, and PRP in combination with other modalities, such as ACell and microneedling. While numerous PRP systems are on the market, no comparison studies exist. Patient selection, proper evaluation, and maintenance are key to successful outcomes. PRP for hair restoration is a valuable addition to a dermatology practice and with newer protocols in place it can easily be incorporated into a busy practice.

Ms Bellomo is owner and chief executive officer of Allele Medical and Bellomo Consulting in Orlando, FL.
Dr Rapaport is in practice in Englewood Cliffs, NJ, where he offers PRP therapy for hair loss.  


References
1. Ellis JA, Sinclair R, Harrap SB. Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med. 2002;4(22):1-11.
2. Rogers NE, Avram MR. Medical treatments for male and female pattern hair loss. J Am Acad Dermatol. 2008;59(4):547-566.
3. American Hair Loss Association website. www.americanhairloss.org. Accessed February 24, 2017.
4. Avci P, Gupta GK, Clark J, Wikonkal N, Hamblin MR. Low-level laser (light) therapy (LLLT) for treatment of hair loss. Lasers Surg Med. 2014;46(2):144-151.
5. Dinh QA, Sinclair R. Female pattern hair loss: current treatment concepts. Clin Inter Aging. 2007;2(2):189-199.
6. Maria-Angeliki G, Alexandros-Efstratios K, Dimitris R, Konstantinos K. Platelet-rich plasma as a potential treatment for noncicatricial alopecias. Int J Trichol. 2015;7(2):54-63.
7. Gupta AK, Carviel JL. Meta-analysis of efficacy of platelet-rich plasma therapy for androgenetic alopecia. J Dermatolog Treat. 2017;28(1):55-58.
8. Anitua E, Pino A, Martinez N, Orive G, Berridi D. The effect of plasma rich in growth factors on pattern hair loss: a pilot study [published online February 17, 2017]. Dermatol Surg. doi:10.1097/DSS.0000000000001049
9. Gupta AK, Carviel J. A mechanistic model of platelet-rich plasma treatment for androgenetic alopecia. Dermatol Surg. 2016;42(12):1335-1339.
10. Ferneini EM, Beauvais D, Castiglione C, Ferneini MV. Platelet-rich plasma in androgenic alopecia: indications, technique, and potential benefits [published online November 15, 2016]. J Oral Maxillofac Surg. pii:S0278-2391(16)31170-3. doi: 10.1016/j.joms.2016.10.040
11. Gentile P, Garcovich S, Bielli A, Scioli MG, Orlandi A, Cervelli V. The effect of platelet-rich plasma in hair regrowth: a randomized placebo-controlled trial. Stem Cells Transl Med. 2015;4(11):1317-1323.
12. Garg S. Outcome of intra-operative injected platelet-rich plasma therapy during follicular unit extraction hair transplant: a prospective randomized study in forty patients. J Cutan Aesthet Surg. 2016;9(3):157-164.
13. Ranaweera A. Platelet-rich plasma. www.dermnetnz.org/topics/platelet-rich-plasma-dermatological-applications. 2013. Accessed February 24, 2017.
14. Rapaport J. Non-invasive solution to reverse male and female hair loss. www.cosmeticskin.com/prp-in-new-jersey-hair-restoration-and-rejuvenation/. October 24, 2015. Accessed February 24, 2017.
15. Does Acell MatriStem and PRP result in genuine hair regeneration? Stem Cell Baldness Cures website. https://stemcellbaldnesscures.com/acell-matristem-2/does-acell-matristem-prp-result-in-genuine-hair-regeneration. Accessed February 24, 2017.
16. Sasaki GH. Micro-needling depth penetration, presence of pigment particles, and fluorescein-stained platelets: clinical usage for aesthetic concerns. Aesthet Surg J. 2017;37(1):71-83.

 

Hair loss affects both men and women and can have a significant impact on quality of life, both personally and professionally. The most common type of hair loss is androgenic alopecia (AGA). It affects up to 50% of white individuals by age 50 and nearly 50% of women over the course of their lifetime.1,2 AGA is progressive, leading to a decrease in the density and diameter of the hair, miniaturization of the hair follicle, and potentially significant baldness. Men and women experiencing balding report a lack of self-esteem and confidence. The lack of confidence and increasing embarrassment often affects their interpersonal relationships and even their professional growth.3

Although men and women are both affected by their hair loss, there are many differences, including presentation, prevalence, and pathophysiology.

Male Pattern Hair Loss
AGA accounts for 95% of the hair loss in men. Male pattern hair loss (MPHL) is caused by an underlying genetic factor that makes the hair follicle sensitive to dihydrotestosterone (DHT). This will cause progressive thinning of the hair and miniaturization of the hair follicle leading to the inability to grow thick, full hair. When considering treatment, it is important to understand how far the hair loss has progressed and this can be done by using the Norwood Scale and a densitometry.3 Male pattern baldness is typically characterized by a receding hairline at the temples and thinning at the scalp vertex, but differing patterns exist.

Treatment options for MPHL include minoxidil 5%, finasteride, ketoconazole 2% shampoo, low-level laser (light) therapy (LLLT),4 surgical hair restoration, nonsurgical hair restoration with platelet-rich plasma (PRP), PRP and ACell, microneedling (pen or roller), topical hair products (ie, Qilib or Revivogen), oral supplements (ie, Viviscal or Nutrafol), and topical growth factors.

Female Pattern Hair Loss
The prevalence of female pattern hair loss (FPHL) appears to advance with age and menopause. Twelve percent of women first develop clinically detectable FPHL by age 29 years, 25% by age 49 years, 41% by 69 years, and more than 50% have some element of FPHL by 79 years of age.5 As women approach menopause, their estrogen levels decline and levels of androgens can increase causing a relative increase in DHT. Lab results may not reflect abnormal androgen levels; therefore, the health  care provider does not relate the hair loss to an overproduction of androgens. These women—just like men—have a genetic propensity for follicular miniaturization. Because women present differently on clinical exam, it is important to use the Ludwig, Savin, or Olsen Scale to determine the progression of hair loss.5

Presentation may include a thinning and widening of the midline part with minimal disruption to the frontal and temporal regions. Women can also present with diffuse thinning, which makes it more difficult to diagnose.5 Therefore, it is necessary to rule out underlying androgen-secreting tumors, endocrine disorders, medication-induced alopecia, telogen effluvium, alopecia areata, as well as inflammatory and autoimmune disorders.3 Women often have multifactorial causes related to hair loss.

The recommended diagnostic tests for women include hormone levels (dehydroepiandrosterone, total testosterone, androstenedione, prolactin, follicle-stimulating hormone, and luteinizing hormone); comprehensive metabolic panel; zinc; Lyme disease screen; serum iron; serum ferritin; total iron binding capacity; thyroid-stimulating hormone (T3, T4,); VDRL test (a screening test for syphilis); complete blood count; scalp biopsy; hair pull; and densitometry.3

Minoxidil (2% and 5%) is the only FDA-approved medication for women. Other treatment options for women include aldactone/spironolactone; estrogen/progesterone; oral contraceptives (caution in women older than 35 years); ketoconazole 2% shampoo; finasteride (contraindicated in women of childbearing age); LLLT;4 surgical hair restoration; nonsurgical hair restoration with PRP; PRP and ACell; microneedling (pen or roller); topical hair products (ie, Qilib or Revivogen); oral supplements (ie, Viviscal or Nutrafol); and topical growth factors.

Platelet-Rich Plasma
PRP is a method for the treatment of AGA that has shown positive results.6-12 (See Figures 1A-C and Figures 2A-B.) PRP is not FDA approved for the use in hair restoration, but certain PRP systems are FDA cleared. PRP is defined as an autologous high concentration of platelets in a small volume of plasma measured as 1,000,000 platelets per microliter of blood or at least 2 times the native concentration of whole blood.6,13

PRP contains platelets that are key to stimulating hair follicles to generate hair growth. The platelets in PRP become activated when injected into the scalp, releasing a variety of growth factors that bind in the bulge of the hair follicle, promoting hair growth.6,9,14 The platelets, when used to regenerate hair growth within follicles, promote healing and the formation of new cell growth. In addition, the platelets accelerate the rate and degree of regeneration so that you can expect to see telogen hairs cycle to anagen in a timely manner. There is also a prolonging of the anagen phase. This is a component of hair restoration because it is effective in stimulating inactive hair follicles, causing them to revert to the growth phase.6,14

Growth factors within PRP that assist in the process of natural hair restoration include11,13,14:

• Platelet-derived growth factor—promotes blood vessel growth, cell replication, skin formation
• Transforming growth factor-b—promotes growth of matrix between cells, bone metabolism
• Vascular endothelial growth factor—promotes blood vessel formation
• Epidermal growth factor—promotes cell growth and differentiation, blood vessel formation, collagen formation
• Fibroblast growth factor-2—promotes growth of specialized cells and blood vessel formation
• Insulinlike growth factor—a regulator of normal physiology in nearly every type of cell in the body

When PRP was first used in nonsurgical hair restoration, it was time-consuming, uncomfortable to the patient, and less cost-effective than current methods. With the introduction of a new technique using subdermal depo bolus injections, hair restoration with PRP is less painful, less traumatic than intradermal injections, and is overall a more efficient injection technique. Subdermal depo bolus administration allows for diffusion of the PRP resulting in fewer injections.14

Starting PRP Therapy for AGA
First and foremost, ensure that you have diagnosed the patient correctly and categorize the type of hair loss your patient is experiencing (Tables 1 and 2).3

Next, make sure you have the proper supplies and medical staff who are proficient in phlebotomy (Table 3). Specimen handling is critical for proper outcomes. Proper labeling and identification is critical at each step. Do not invert the test tube once removed from centrifuge. Keep upright so the less concentrated

PRP can be drawn off and the 5 times concentrated PRP is left in the test tube. The highly concentrated PRP is key to the success of hair restoration.

The injection protocol includes:

1.    Draw blood into appropriate size PRP tube (22 mL)
2.    Invert several times mixing the anticoagulant into the blood
3.    Centrifuge for 10 minutes (See centrifuge instructions for speed recommendation)
4.    Draw off 6 ccs of platelet-poor plasma using a 10-cc syringe and rigid 50-mm needle, leaving behind 5 to 6 cc of PRP
5.    Optional—Add 0.1 mL lidocaine to new 10-mL syringe
6.    Invert tube 7 to 10 times, mixing the platelets with remaining plasma
7.    Draw up PRP using 10-cc syringe and Vacutainer Transfer Device
8.    Lie patient down and have them identify their blood
9.    Apply chiller to point of care
10.    Use 27g ½-in needle and inject approximately 0.3 to 0.5 mL PRP subdermally across areas of hair loss
11.    Treat once per month for first 3 to 4 months followed by maintenance treatment every 4 to 6 months

The key to this technique is ensuring you are injecting into the subdermal space, which will allow the PRP to enter this space with ease and with minimal discomfort to the patient.

Other Considerations
Setting expectations is another important factor to success. Like any procedure, results can vary between individuals. PRP does not work for everyone; the longer the hair has been dormant the less it responds. But in many instances, patients start to see results within 60 days of the first injection session.

Women in particular may take much longer before seeing results. Because AGA is a chronic, progressive genetic disorder, maintenance with PRP is a necessity for long-term success.

It is recommended patients have a treatment every 3 to 4 weeks for the first 4 months. At this point, they will enter into the maintenance phase. The patient should return every 6 months for PRP treatment. Limiting factors for treatment maintenance may be cost and time.

The cost of PRP ranges from $600 to $900 per treatment. Creating a package for the patient to include the first year of maintenance sessions will increase compliance through the maintenance phase. As such, PRP for hair restoration can significantly increase the revenue of your practice.

Other considerations include safety, contraindications, and complications. PRP is immunologically neutral and poses no danger of allergy, hypersensitivity, or foreign-body reactions. Sterile technique must be used at every stage of PRP preparation and application to reduce the risk of infection, which is not commonly seen. If administered by intradermal injection, a brief period of inflammation at the wound site may be experienced. Subdermal injection is advised. Nerve trauma and hematoma are other potential complications.1

Contraindication for use of PRP include critical thrombocytopenia (low platelet count); hypofibrinogenemia, hemodynamic instability (collapse); infection (sepsis); acute and chronic infections; chronic liver disease; anticoagulation therapy (warfarin, dabigatran, heparin); and scarring alopecia.13

Combination Treatments
Physicians who perform hair restoration often use PRP in combination with ACell, a non-cross-linked, completely resorbable, acellular extracellular matrix that also is used in wound healing. The protein in ACell is developed and manufactured from pig’s bladder.15 Therefore, it should be avoided in those with an allergy to porcine material and patients could possibly have a foreignbody reaction to the material. Some practitioners believe that this combination of PRP with ACell will prolong the effects of PRP and improve results.15

Microneedling is also commonly used in the treatment of hair loss and is an adjunct to PRP which is thought to prolong the effects of PRP and improve results.8 Microneedling can be done at the time of treatment or at home with a microneedling roller. When recommending a roller, it is advised to stay at a depth of 0.25 mm, which is the FDA-approved depth for microneedling rollers. Advise your patients to avoid purchasing rollers online that are at a greater depth of 0.25 mm.16

Conclusion
PRP is making advances in hair restoration, but is still in its early stages. An increasing need for more peer-reviewed studies exists to evaluate the efficacy and safety of PRP, PRP protocols, and PRP in combination with other modalities, such as ACell and microneedling. While numerous PRP systems are on the market, no comparison studies exist. Patient selection, proper evaluation, and maintenance are key to successful outcomes. PRP for hair restoration is a valuable addition to a dermatology practice and with newer protocols in place it can easily be incorporated into a busy practice.

Ms Bellomo is owner and chief executive officer of Allele Medical and Bellomo Consulting in Orlando, FL.
Dr Rapaport is in practice in Englewood Cliffs, NJ, where he offers PRP therapy for hair loss.  


References
1. Ellis JA, Sinclair R, Harrap SB. Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med. 2002;4(22):1-11.
2. Rogers NE, Avram MR. Medical treatments for male and female pattern hair loss. J Am Acad Dermatol. 2008;59(4):547-566.
3. American Hair Loss Association website. www.americanhairloss.org. Accessed February 24, 2017.
4. Avci P, Gupta GK, Clark J, Wikonkal N, Hamblin MR. Low-level laser (light) therapy (LLLT) for treatment of hair loss. Lasers Surg Med. 2014;46(2):144-151.
5. Dinh QA, Sinclair R. Female pattern hair loss: current treatment concepts. Clin Inter Aging. 2007;2(2):189-199.
6. Maria-Angeliki G, Alexandros-Efstratios K, Dimitris R, Konstantinos K. Platelet-rich plasma as a potential treatment for noncicatricial alopecias. Int J Trichol. 2015;7(2):54-63.
7. Gupta AK, Carviel JL. Meta-analysis of efficacy of platelet-rich plasma therapy for androgenetic alopecia. J Dermatolog Treat. 2017;28(1):55-58.
8. Anitua E, Pino A, Martinez N, Orive G, Berridi D. The effect of plasma rich in growth factors on pattern hair loss: a pilot study [published online February 17, 2017]. Dermatol Surg. doi:10.1097/DSS.0000000000001049
9. Gupta AK, Carviel J. A mechanistic model of platelet-rich plasma treatment for androgenetic alopecia. Dermatol Surg. 2016;42(12):1335-1339.
10. Ferneini EM, Beauvais D, Castiglione C, Ferneini MV. Platelet-rich plasma in androgenic alopecia: indications, technique, and potential benefits [published online November 15, 2016]. J Oral Maxillofac Surg. pii:S0278-2391(16)31170-3. doi: 10.1016/j.joms.2016.10.040
11. Gentile P, Garcovich S, Bielli A, Scioli MG, Orlandi A, Cervelli V. The effect of platelet-rich plasma in hair regrowth: a randomized placebo-controlled trial. Stem Cells Transl Med. 2015;4(11):1317-1323.
12. Garg S. Outcome of intra-operative injected platelet-rich plasma therapy during follicular unit extraction hair transplant: a prospective randomized study in forty patients. J Cutan Aesthet Surg. 2016;9(3):157-164.
13. Ranaweera A. Platelet-rich plasma. www.dermnetnz.org/topics/platelet-rich-plasma-dermatological-applications. 2013. Accessed February 24, 2017.
14. Rapaport J. Non-invasive solution to reverse male and female hair loss. www.cosmeticskin.com/prp-in-new-jersey-hair-restoration-and-rejuvenation/. October 24, 2015. Accessed February 24, 2017.
15. Does Acell MatriStem and PRP result in genuine hair regeneration? Stem Cell Baldness Cures website. https://stemcellbaldnesscures.com/acell-matristem-2/does-acell-matristem-prp-result-in-genuine-hair-regeneration. Accessed February 24, 2017.
16. Sasaki GH. Micro-needling depth penetration, presence of pigment particles, and fluorescein-stained platelets: clinical usage for aesthetic concerns. Aesthet Surg J. 2017;37(1):71-83.

 

Hair loss affects both men and women and can have a significant impact on quality of life, both personally and professionally. The most common type of hair loss is androgenic alopecia (AGA). It affects up to 50% of white individuals by age 50 and nearly 50% of women over the course of their lifetime.1,2 AGA is progressive, leading to a decrease in the density and diameter of the hair, miniaturization of the hair follicle, and potentially significant baldness. Men and women experiencing balding report a lack of self-esteem and confidence. The lack of confidence and increasing embarrassment often affects their interpersonal relationships and even their professional growth.3

Although men and women are both affected by their hair loss, there are many differences, including presentation, prevalence, and pathophysiology.

Male Pattern Hair Loss
AGA accounts for 95% of the hair loss in men. Male pattern hair loss (MPHL) is caused by an underlying genetic factor that makes the hair follicle sensitive to dihydrotestosterone (DHT). This will cause progressive thinning of the hair and miniaturization of the hair follicle leading to the inability to grow thick, full hair. When considering treatment, it is important to understand how far the hair loss has progressed and this can be done by using the Norwood Scale and a densitometry.3 Male pattern baldness is typically characterized by a receding hairline at the temples and thinning at the scalp vertex, but differing patterns exist.

Treatment options for MPHL include minoxidil 5%, finasteride, ketoconazole 2% shampoo, low-level laser (light) therapy (LLLT),4 surgical hair restoration, nonsurgical hair restoration with platelet-rich plasma (PRP), PRP and ACell, microneedling (pen or roller), topical hair products (ie, Qilib or Revivogen), oral supplements (ie, Viviscal or Nutrafol), and topical growth factors.

Female Pattern Hair Loss
The prevalence of female pattern hair loss (FPHL) appears to advance with age and menopause. Twelve percent of women first develop clinically detectable FPHL by age 29 years, 25% by age 49 years, 41% by 69 years, and more than 50% have some element of FPHL by 79 years of age.5 As women approach menopause, their estrogen levels decline and levels of androgens can increase causing a relative increase in DHT. Lab results may not reflect abnormal androgen levels; therefore, the health  care provider does not relate the hair loss to an overproduction of androgens. These women—just like men—have a genetic propensity for follicular miniaturization. Because women present differently on clinical exam, it is important to use the Ludwig, Savin, or Olsen Scale to determine the progression of hair loss.5

Presentation may include a thinning and widening of the midline part with minimal disruption to the frontal and temporal regions. Women can also present with diffuse thinning, which makes it more difficult to diagnose.5 Therefore, it is necessary to rule out underlying androgen-secreting tumors, endocrine disorders, medication-induced alopecia, telogen effluvium, alopecia areata, as well as inflammatory and autoimmune disorders.3 Women often have multifactorial causes related to hair loss.

The recommended diagnostic tests for women include hormone levels (dehydroepiandrosterone, total testosterone, androstenedione, prolactin, follicle-stimulating hormone, and luteinizing hormone); comprehensive metabolic panel; zinc; Lyme disease screen; serum iron; serum ferritin; total iron binding capacity; thyroid-stimulating hormone (T3, T4,); VDRL test (a screening test for syphilis); complete blood count; scalp biopsy; hair pull; and densitometry.3

Minoxidil (2% and 5%) is the only FDA-approved medication for women. Other treatment options for women include aldactone/spironolactone; estrogen/progesterone; oral contraceptives (caution in women older than 35 years); ketoconazole 2% shampoo; finasteride (contraindicated in women of childbearing age); LLLT;4 surgical hair restoration; nonsurgical hair restoration with PRP; PRP and ACell; microneedling (pen or roller); topical hair products (ie, Qilib or Revivogen); oral supplements (ie, Viviscal or Nutrafol); and topical growth factors.

Platelet-Rich Plasma
PRP is a method for the treatment of AGA that has shown positive results.6-12 (See Figures 1A-C and Figures 2A-B.) PRP is not FDA approved for the use in hair restoration, but certain PRP systems are FDA cleared. PRP is defined as an autologous high concentration of platelets in a small volume of plasma measured as 1,000,000 platelets per microliter of blood or at least 2 times the native concentration of whole blood.6,13

PRP contains platelets that are key to stimulating hair follicles to generate hair growth. The platelets in PRP become activated when injected into the scalp, releasing a variety of growth factors that bind in the bulge of the hair follicle, promoting hair growth.6,9,14 The platelets, when used to regenerate hair growth within follicles, promote healing and the formation of new cell growth. In addition, the platelets accelerate the rate and degree of regeneration so that you can expect to see telogen hairs cycle to anagen in a timely manner. There is also a prolonging of the anagen phase. This is a component of hair restoration because it is effective in stimulating inactive hair follicles, causing them to revert to the growth phase.6,14

Growth factors within PRP that assist in the process of natural hair restoration include11,13,14:

• Platelet-derived growth factor—promotes blood vessel growth, cell replication, skin formation
• Transforming growth factor-b—promotes growth of matrix between cells, bone metabolism
• Vascular endothelial growth factor—promotes blood vessel formation
• Epidermal growth factor—promotes cell growth and differentiation, blood vessel formation, collagen formation
• Fibroblast growth factor-2—promotes growth of specialized cells and blood vessel formation
• Insulinlike growth factor—a regulator of normal physiology in nearly every type of cell in the body

When PRP was first used in nonsurgical hair restoration, it was time-consuming, uncomfortable to the patient, and less cost-effective than current methods. With the introduction of a new technique using subdermal depo bolus injections, hair restoration with PRP is less painful, less traumatic than intradermal injections, and is overall a more efficient injection technique. Subdermal depo bolus administration allows for diffusion of the PRP resulting in fewer injections.14

Starting PRP Therapy for AGA
First and foremost, ensure that you have diagnosed the patient correctly and categorize the type of hair loss your patient is experiencing (Tables 1 and 2).3

Next, make sure you have the proper supplies and medical staff who are proficient in phlebotomy (Table 3). Specimen handling is critical for proper outcomes. Proper labeling and identification is critical at each step. Do not invert the test tube once removed from centrifuge. Keep upright so the less concentrated

PRP can be drawn off and the 5 times concentrated PRP is left in the test tube. The highly concentrated PRP is key to the success of hair restoration.

The injection protocol includes:

1.    Draw blood into appropriate size PRP tube (22 mL)
2.    Invert several times mixing the anticoagulant into the blood
3.    Centrifuge for 10 minutes (See centrifuge instructions for speed recommendation)
4.    Draw off 6 ccs of platelet-poor plasma using a 10-cc syringe and rigid 50-mm needle, leaving behind 5 to 6 cc of PRP
5.    Optional—Add 0.1 mL lidocaine to new 10-mL syringe
6.    Invert tube 7 to 10 times, mixing the platelets with remaining plasma
7.    Draw up PRP using 10-cc syringe and Vacutainer Transfer Device
8.    Lie patient down and have them identify their blood
9.    Apply chiller to point of care
10.    Use 27g ½-in needle and inject approximately 0.3 to 0.5 mL PRP subdermally across areas of hair loss
11.    Treat once per month for first 3 to 4 months followed by maintenance treatment every 4 to 6 months

The key to this technique is ensuring you are injecting into the subdermal space, which will allow the PRP to enter this space with ease and with minimal discomfort to the patient.

Other Considerations
Setting expectations is another important factor to success. Like any procedure, results can vary between individuals. PRP does not work for everyone; the longer the hair has been dormant the less it responds. But in many instances, patients start to see results within 60 days of the first injection session.

Women in particular may take much longer before seeing results. Because AGA is a chronic, progressive genetic disorder, maintenance with PRP is a necessity for long-term success.

It is recommended patients have a treatment every 3 to 4 weeks for the first 4 months. At this point, they will enter into the maintenance phase. The patient should return every 6 months for PRP treatment. Limiting factors for treatment maintenance may be cost and time.

The cost of PRP ranges from $600 to $900 per treatment. Creating a package for the patient to include the first year of maintenance sessions will increase compliance through the maintenance phase. As such, PRP for hair restoration can significantly increase the revenue of your practice.

Other considerations include safety, contraindications, and complications. PRP is immunologically neutral and poses no danger of allergy, hypersensitivity, or foreign-body reactions. Sterile technique must be used at every stage of PRP preparation and application to reduce the risk of infection, which is not commonly seen. If administered by intradermal injection, a brief period of inflammation at the wound site may be experienced. Subdermal injection is advised. Nerve trauma and hematoma are other potential complications.1

Contraindication for use of PRP include critical thrombocytopenia (low platelet count); hypofibrinogenemia, hemodynamic instability (collapse); infection (sepsis); acute and chronic infections; chronic liver disease; anticoagulation therapy (warfarin, dabigatran, heparin); and scarring alopecia.13

Combination Treatments
Physicians who perform hair restoration often use PRP in combination with ACell, a non-cross-linked, completely resorbable, acellular extracellular matrix that also is used in wound healing. The protein in ACell is developed and manufactured from pig’s bladder.15 Therefore, it should be avoided in those with an allergy to porcine material and patients could possibly have a foreignbody reaction to the material. Some practitioners believe that this combination of PRP with ACell will prolong the effects of PRP and improve results.15

Microneedling is also commonly used in the treatment of hair loss and is an adjunct to PRP which is thought to prolong the effects of PRP and improve results.8 Microneedling can be done at the time of treatment or at home with a microneedling roller. When recommending a roller, it is advised to stay at a depth of 0.25 mm, which is the FDA-approved depth for microneedling rollers. Advise your patients to avoid purchasing rollers online that are at a greater depth of 0.25 mm.16

Conclusion
PRP is making advances in hair restoration, but is still in its early stages. An increasing need for more peer-reviewed studies exists to evaluate the efficacy and safety of PRP, PRP protocols, and PRP in combination with other modalities, such as ACell and microneedling. While numerous PRP systems are on the market, no comparison studies exist. Patient selection, proper evaluation, and maintenance are key to successful outcomes. PRP for hair restoration is a valuable addition to a dermatology practice and with newer protocols in place it can easily be incorporated into a busy practice.

Ms Bellomo is owner and chief executive officer of Allele Medical and Bellomo Consulting in Orlando, FL.
Dr Rapaport is in practice in Englewood Cliffs, NJ, where he offers PRP therapy for hair loss.  


References
1. Ellis JA, Sinclair R, Harrap SB. Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med. 2002;4(22):1-11.
2. Rogers NE, Avram MR. Medical treatments for male and female pattern hair loss. J Am Acad Dermatol. 2008;59(4):547-566.
3. American Hair Loss Association website. www.americanhairloss.org. Accessed February 24, 2017.
4. Avci P, Gupta GK, Clark J, Wikonkal N, Hamblin MR. Low-level laser (light) therapy (LLLT) for treatment of hair loss. Lasers Surg Med. 2014;46(2):144-151.
5. Dinh QA, Sinclair R. Female pattern hair loss: current treatment concepts. Clin Inter Aging. 2007;2(2):189-199.
6. Maria-Angeliki G, Alexandros-Efstratios K, Dimitris R, Konstantinos K. Platelet-rich plasma as a potential treatment for noncicatricial alopecias. Int J Trichol. 2015;7(2):54-63.
7. Gupta AK, Carviel JL. Meta-analysis of efficacy of platelet-rich plasma therapy for androgenetic alopecia. J Dermatolog Treat. 2017;28(1):55-58.
8. Anitua E, Pino A, Martinez N, Orive G, Berridi D. The effect of plasma rich in growth factors on pattern hair loss: a pilot study [published online February 17, 2017]. Dermatol Surg. doi:10.1097/DSS.0000000000001049
9. Gupta AK, Carviel J. A mechanistic model of platelet-rich plasma treatment for androgenetic alopecia. Dermatol Surg. 2016;42(12):1335-1339.
10. Ferneini EM, Beauvais D, Castiglione C, Ferneini MV. Platelet-rich plasma in androgenic alopecia: indications, technique, and potential benefits [published online November 15, 2016]. J Oral Maxillofac Surg. pii:S0278-2391(16)31170-3. doi: 10.1016/j.joms.2016.10.040
11. Gentile P, Garcovich S, Bielli A, Scioli MG, Orlandi A, Cervelli V. The effect of platelet-rich plasma in hair regrowth: a randomized placebo-controlled trial. Stem Cells Transl Med. 2015;4(11):1317-1323.
12. Garg S. Outcome of intra-operative injected platelet-rich plasma therapy during follicular unit extraction hair transplant: a prospective randomized study in forty patients. J Cutan Aesthet Surg. 2016;9(3):157-164.
13. Ranaweera A. Platelet-rich plasma. www.dermnetnz.org/topics/platelet-rich-plasma-dermatological-applications. 2013. Accessed February 24, 2017.
14. Rapaport J. Non-invasive solution to reverse male and female hair loss. www.cosmeticskin.com/prp-in-new-jersey-hair-restoration-and-rejuvenation/. October 24, 2015. Accessed February 24, 2017.
15. Does Acell MatriStem and PRP result in genuine hair regeneration? Stem Cell Baldness Cures website. https://stemcellbaldnesscures.com/acell-matristem-2/does-acell-matristem-prp-result-in-genuine-hair-regeneration. Accessed February 24, 2017.
16. Sasaki GH. Micro-needling depth penetration, presence of pigment particles, and fluorescein-stained platelets: clinical usage for aesthetic concerns. Aesthet Surg J. 2017;37(1):71-83.

 

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