Platelet-rich plasma
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Platelet-rich plasma (PRP), also known as autologous conditioned plasma, is a concentrate of
platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
-rich
plasma protein Blood-proteins, also termed plasma proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other bl ...
derived from whole
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
, centrifuged to remove
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hol ...
s. Though promoted to treat an array of medical problems, evidence for benefit is mixed as of 2020, with some evidence for use in certain conditions and against use in other conditions. As a concentrated source of
blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the int ...
and autologous conditioned plasma, PRP contains several different
growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regul ...
s and other
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...
s that can stimulate healing of
soft tissue Soft tissue is all the tissue in the body that is not hardened by the processes of ossification or calcification such as bones and teeth. Soft tissue connects, surrounds or supports internal organs and bones, and includes muscle, tendons, ...
and joints. There are some indications for use in sports medicine and orthopedics (acute muscle strains,
tendinopathy Tendinopathy, a type of tendon disorder that results in pain, swelling, and impaired function. The pain is typically worse with movement. It most commonly occurs around the shoulder (rotator cuff tendinitis, biceps tendinitis), elbow (tennis elb ...
and muscle-
fascia A fascia (; plural fasciae or fascias; adjective fascial; from Latin: "band") is a band or sheet of connective tissue, primarily collagen, beneath the skin that attaches to, stabilizes, encloses, and separates muscles and other internal organs ...
l injuries and
osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the ...
), or dermatology (
androgenic alopecia Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...
,
wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...
, and skin rejuvenation) or even in proctology (
fistula-in-ano Anal fistula is a chronic abnormal communication between the epithelialised surface of the anal canal and usually the perianal skin. An anal fistula can be described as a narrow tunnel with its internal opening in the anal canal and its externa ...
). For preparation of PRP, various protocols are used, with an underlying principle of concentrating platelets to 3–5 times physiological levels, then injecting this concentrate in the tissue where healing is desired. Besides the use in clinical practice PRP has been utilized for various tissue engineering applications in the context of bone, cartilage, skin, and soft tissue repair. It has been reviewed to serve as a source for the "delivery of growth factors and/or cells within tissue-engineered constructs, often in combination with biomaterials". The second generation of PRP is known as platelet-rich fibrin (PRF).


Medical use

Evidence for benefit of PRP is mixed, with some evidence for use in certain conditions and against use in other conditions. It has been investigated for chronic
tendinitis Tendinopathy, a type of tendon disorder that results in pain, swelling, and impaired function. The pain is typically worse with movement. It most commonly occurs around the shoulder (rotator cuff tendinitis, biceps tendinitis), elbow (tennis elbo ...
,
osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the ...
, in oral surgery, and in
plastic surgery Plastic surgery is a surgical specialty involving the restoration, reconstruction or alteration of the human body. It can be divided into two main categories: reconstructive surgery and cosmetic surgery. Reconstructive surgery includes cranio ...
. A 2019 review found it not to be useful in
rotator cuff disease A rotator cuff tear is an injury where one or more of the tendons or muscles of the rotator cuff of the shoulder get torn. Symptoms may include shoulder pain, which is often worse with movement, limited range of motion, or weakness. This may limi ...
. While an older review found that it may be useful. Tentative evidence supports its use in
osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the ...
(OA) of the knee. A 2019 meta-analysis found that PRP might be more effective in reducing pain and improving function than
hyaluronic acid Hyaluronic acid (; abbreviated HA; conjugate base hyaluronate), also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglyca ...
in knee OA. A 2009 review found few randomized controlled trials that adequately evaluated the safety and efficacy of PRP treatments and concluded that PRP was "a promising, but not proven, treatment option for joint, tendon, ligament, and muscle injuries". As compared to other conservative treatments for non-surgical orthopedic illnesses (e.g. steroid injection for
plantar fasciitis Plantar fasciitis or plantar heel pain (PHP) is a disorder of the plantar fascia, which is the connective tissue which supports the arch of the foot. It results in pain in the heel and bottom of the foot that is usually most severe with the fi ...
), evidence does not support the use of PRP as a conservative treatment. A 2018 review found that evidence was lacking for
Achilles tendinopathy The Achilles tendon or heel cord, also known as the calcaneal tendon, is a tendon at the back of the lower leg, and is the thickest in the human body. It serves to attach the plantaris, gastrocnemius (calf) and soleus muscles to the calcaneu ...
. A 2019 meta-analysis found that, for most outcomes in Achilles tendinopathy, PRP treatment did not differ from placebo treatment. A 2010 Cochrane review of use in
sinus lift Maxillary sinus floor augmentation (also termed sinus lift, sinus graft, sinus augmentation or sinus procedure) is a surgical procedure which aims to increase the amount of bone in the posterior maxilla (upper jaw bone), in the area of the prem ...
s during
dental implant A dental implant (also known as an endosseous implant or fixture) is a prosthesis that interfaces with the bone of the jaw or skull to support a dental prosthesis such as a crown, bridge, denture, or facial prosthesis or to act as an orthodo ...
placement found no evidence of benefit. A 2013 review stated more evidence was needed to determine effectiveness for hair regrowth. A 2014 Cochrane review of PRP in musculoskeletal injuries found very weak evidence for a decrease in pain in the short term, and no difference in function in the short, medium or long term. There was weak evidence that suggested that harm occurred at comparable, low rates in treated and untreated people. Similarly, another 2017 review for treating pain on skin graft donor sites found the evidence for benefit was poor. It has not been shown to be useful for bone healing. A 2016 review of PRP use to augment bone graft found only one study reporting a difference in bone augmentation, while four studies found no difference.


Adverse effects

Adverse effects have been poorly studied. The single systematic review of the literature did not report of the types and number of adverse events. In 2019, Health Canada stated that most autologous cell therapies have little evidence showing they work and can pose risks, such as cross-contamination between people if equipment is not sterilized properly or potentially dangerous immune reactions. Health Canada stopped Canadian clinics from offering these types of services with a donor-patient model. Health Canada later clarified that PRP treatments harvested from, and given back to, the same person (in a single procedure) was not covered by its initial guidance as the procedure falls under health care provider regulatory bodies (rather than Health Canada).


Composition

There are four general categories of preparation of PRP based on its
leukocyte White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
and
fibrin Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with pl ...
content: leukocyte-rich PRP (L-PRP), leukocyte reduced PRP (P-PRP; leukocyte reduced or pure PRP), leukocyte platelet-rich fibrin and pure platelet-rich fibrin (PRF). The efficacy of certain growth factors in healing various injuries and the concentrations of these growth factors found within PRP are the theoretical basis for the use of PRP in tissue repair. The platelets collected in PRP are activated by the addition of
thrombin Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...
and
calcium chloride Calcium chloride is an inorganic compound, a salt with the chemical formula . It is a white crystalline solid at room temperature, and it is highly soluble in water. It can be created by neutralising hydrochloric acid with calcium hydroxide. Ca ...
, which induces the release of the mentioned factors from
alpha granules Alpha granules, (α-granules) also known as platelet alpha-granules are a cellular component of platelets. Platelets contain different types of granules that perform different functions, and include alpha granules, dense granules, and lysosomes. ...
. The growth factors and other cytokines present in PRP include: *
platelet-derived growth factor Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood v ...
*
transforming growth factor beta Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other ...
*
fibroblast growth factor Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their ...
*
insulin-like growth factor 1 Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults. IGF-1 is a protein that in humans ...
* insulin-like growth factor 2 * vascular endothelial growth factor A *
vascular endothelial growth factor C Vascular endothelial growth factor C (VEGF-C) is a protein that is a member of the platelet-derived growth factor / vascular endothelial growth factor (PDGF/VEGF) family. It is encoded in humans by the ''VEGFC'' gene, which is located on chromos ...
*
epidermal growth factor Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-k Da and has 53 amino acid residues and three intramolecular disulfide bonds. EGF was originally de ...
*
Interleukin 8 Interleukin 8 (IL-8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage ...
*
keratinocyte growth factor The keratinocyte growth factor (KGF), also known as FGF7, is a growth factor present in the epithelialization-phase of wound healing. In this phase, keratinocytes are covering the wound, forming the epithelium. KGF is a small signaling molecul ...
* connective tissue growth factor *
Hepatocyte growth factor Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on ...
* Stromal cell-derived factor 1 *
Endostatin Endostatin is a naturally occurring, 20-kDa C-terminal fragment derived from type XVIII collagen. It is reported to serve as an anti-angiogenic agent, similar to angiostatin and thrombospondin. Endostatin is a broad-spectrum angiogenesis inhibi ...


Manufacturing

PRP is prepared by taking blood from the person, and then putting it through two stages of
centrifugation Centrifugation is a mechanical process which involves the use of the centrifugal force to separate particles from a solution according to their size, shape, density, medium viscosity and rotor speed. The denser components of the mixture migrate ...
designed to separate PRP from platelet-poor plasma and
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hol ...
s. This is usually done by the clinic offering the treatment, using commercially available kits and equipment. The resulting substance varies from person to person and from facility to facility, making it difficult to understand how safe and effective any specific use is. File:Blood drawn from patient.JPG, Blood drawn from patient File:Removal of PRP after double centrifugation.JPG, Removal of PRP after double centrifugation File:PRP is Injected into area of injury via ultrasound guidance.JPG, PRP is Injected into area of injury via ultrasound guidance


Society and culture

PRP has received attention in the popular media as a result of its use by athletes. Use in an office setting is not approved by the FDA. In the 2010s, contentious cosmetic procedures marketed under the name of "vampire facials" grew in popularity, fueled by celebrity endorsement. These "vampire facials" generally center on PRP treatment, and usually (but not always) involve
microneedling Collagen induction therapy (CIT), also known as microneedling, dermarolling, or skin needling, is a cosmetic procedure that involves repeatedly puncturing the skin with tiny, sterile needles (microneedling the skin). CIT should be separated from o ...
. PRP has also been injected into the
vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...
, in a procedure called "O-shot" or "orgasm shot", with claims that this will improve
orgasm Orgasm (from Greek , ; "excitement, swelling") or sexual climax is the sudden discharge of accumulated sexual excitement during the sexual response cycle, resulting in rhythmic, involuntary muscular contractions in the pelvic region chara ...
s. There is no evidence, however, to support these claims. There are concerns from researchers studying PRP that it may be overused in a clinical setting including by for-profit unproven stem cell clinics, which market it for dozens of conditions mostly without evidence.


Doping

Some concern exists as to whether PRP treatments violate anti- doping rules. As of 2010, it was not clear if local injections of PRP could have a systemic impact on circulating
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...
levels, affecting doping tests and whether PRP treatments have systemic anabolic effects or affect performance. In January 2011, the
World Anti-Doping Agency The World Anti-Doping Agency (WADA; french: Agence mondiale antidopage, AMA) is a foundation initiated by the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against drugs in sports. The agency's key ...
removed intramuscular injections of PRP from its prohibitions after determining that there is a "lack of any current evidence concerning the use of these methods for purposes of performance enhancement".


History

In the early 1940s clinicians used extracts of growth factors and cytokines for healing. The term 'platet-rich plasma' was first used in 1954 by Kingsley and in the 1960s the first PRP blood banks were established, becoming popular by the 1970s. In the 1970s PRP was used in the field of hematology, originally for transfusions to treat
thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...
. Ten years later it was used for maxillofacial surgeries. PRP was first used in Italy in 1987 in an open heart surgery procedure. Ferrari M, Zia S, Valbonesi M, Henriquet F, Venere G, Spagnolo S, Grasso MA, Panzani I. A new technique for hemodilution, preparation of autologous platelet-rich plasma and intraoperative blood salvage in cardiac surgery. Int J Artif Organs. 1987 Jan;10(1):47-50. PMID: 3570542 In 2006 PRP was starting to be considered of potential use for both
androgenic alopecia Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...
and
alopecia areata Alopecia areata, also known as spot baldness, is a condition in which hair is lost from some or all areas of the body. Often, it results in a few bald spots on the scalp, each about the size of a coin. Psychological stress and illness are pos ...
, though research remained mixed.


See also

* Autologous blood injection *
Autologous conditioned serum Autologous conditioned serum, also known as Orthokine and Regenokine, is an experimental procedure in which a person's own blood is extracted, manipulated, and then reintroduced with claimed benefit in osteoarthritis. There is limited evidence on sa ...
*
Hypoxia preconditioned plasma Hypoxia preconditioned plasma or hypoxia pre-conditioned plasma (abbreviated as HPP) is the (cell-free) plasma obtained after extracorporeal An extracorporeal is a medical procedure which is performed outside the body. Extracorporeal devices a ...
* Platelet-rich fibrin matrix * Platelet swirling


References

{{DEFAULTSORT:Platelet-Rich Plasma Blood products Transfusion medicine