Abstract: Platelet-rich plasma (PRP) is defined as a small volume of plasma containing platelets in higher concentrations than those found in peripheral blood and was initially used as a transfusion product for the treatment of thrombocytopenia. To date, several growth factors and cytokines have been discovered that can accelerate wound healing and tissue regeneration, leading to a wider range of applications in medicine, such as sports medicine, regenerative medicine, and aesthetic medicine. Many studies have shown that PRP can be effectively used in the treatment of hair loss. Despite its widespread use, the exact mechanism of action of PRP is still not fully elucidated. In this article, we aim to review and update current information on the definition, classification, mechanism of action, clinical efficacy in hair growth, and side effects of PRP.

Keywords: platelet-rich plasma, androgenetic alopecia, female pattern hair loss, alopecia areata, cicatricial alopecia, hair transplantation.

Introduction
Platelet-rich plasma (PRP) was first defined in Hematology as a small volume of plasma containing higher concentrations of platelets than those found in peripheral blood and was first used as a transfusion product for the treatment of thrombocytopenia since the 1970s.(1) Today, PRP has become a popular treatment in sports medicine, (2) regenerative medicine, (2,3) aesthetic medicine (4) and hair loss treatment (5,6) and many other fields, as it contains various growth factors and cytokines that can accelerate wound healing and tissue restoration. Both the device used to separate the platelets and the subsequent use of the PRP product are covered by the regulation of the U.S. Food and Drug Administration (FDA).(7) Any use of PRP other than blood transfusion is an “off-label use” not prohibited under FDA regulation if performed by a physician with the intention of practicing medicine. Despite its widespread application, the mechanism underlying the hair growth effects of PRP is yet to be fully discovered. We aim to review the effectiveness of PRP as a hair loss treatment, including its definition, classification, mechanism of action, clinical efficacy in hair regrowth, and side effects.

Definition
Platelet-rich plasma (PRP), also known as platelet-rich growth factors or platelet concentrate, is a concentrate of platelet-rich plasma protein obtained from whole blood that has been centrifuged to remove red blood cells. In addition to the main component containing high concentrations of platelets, there are other components such as the presence or absence of leukocyte and platelet activating agents used to define different types of PRP. The effectiveness of stimulating tissue regeneration depends on the concentration of platelets present in the plasma; several studies have shown that concentrations 4 to 6 times higher than normal platelet counts are required for optimal results.

Preparation
Since there is no standard method for preparing and applying PRP, there are a wide variety of preparation methods. However, the basic principle is to prepare concentrated platelets from the patient's own blood. All PRP preparation protocols follow a general procedure starting with the collection of approximately 10 to 60 mL of venous blood from the patient and its placement into tubes containing an anticoagulant, acid citrate dextrose or sodium citrate solution to prevent clotting and premature release of alpha granules. The whole blood is then centrifuged and separated into 3 layers according to specific gravity, the bottom layer containing red blood cells with leukocytes (RBCs), the middle layer being PRP, and the top layer being platelet-poor plasma (PPP). (9) There are various commercial PRP kits that simplify PRP preparation. These kits differ in terms of platelet concentrations, presence of leukocytes, and platelet activator, leading to variations in growth factor concentrations. All of this explains the variability in the clinical benefits of PRP reported in the literature. Some studies have induced growth factor release and alpha granule degradation by adding calcium gluconate, calcium chloride, or thrombin before application (activated PRP). There is no consensus on whether exogenous activation of platelets or the use of host thrombin as an endogenous activator is necessary to maximize the therapeutic effect. (10 12) Platelet alpha granules release growth factors within 10 minutes after coagulation or activation, therefore 10-minute activation is recommended for maximum benefit in PRP therapy. (13)

Classification of Platelet-Rich Plasma
There are many variations in PRP preparations such as the type of collection tubes, the power used, the number of cycles and centrifugation time, the PRP components, and the activation method applied. A standardized PRP classification called DEPA, based on four components, was developed by Magalon et al.