Platelet-rich plasma
Encyclopedia
Platelet-rich plasma is blood plasma
that has been enriched with platelet
s. As a concentrated source of autologous platelets, PRP contains (and releases through degranulation
) several different growth factor
s and other cytokine
s that stimulate healing of bone and soft tissue
.
and calcium chloride
, which induces the release of these factors from alpha granules
. The growth factors and other cytokines present in PRP include:
. Both processes involve the collection of whole blood
that is anticoagulated
with citrate dextrose
) before undergoing two stages of centrifugation
designed to separate the PRP aliquot from platelet-poor plasma and red blood cell
s. In humans, the typical baseline blood platelet count is approximately 200,000 per µL
; therapeutic PRP concentrates the platelets by roughly five-fold. There is however broad variability in the production of PRP by various concentrating equipment and techniques.
, tendinitis, cardiac muscle
injury, bone repair and regeneration, plastic surgery
, and oral surgery
. PRP has also received attention in the popular media as a result of its use in treating sports injuries in professional athletes.
have not yet been confirmed in large-scale controlled
clinical trial
s. For example, clinical use of PRP for nerve injury and sports medicine has produced "promising" but "inconsistent" results in early trials. A 2009 systematic review
of the scientific literature stated that there are few controlled
clinical trial
s that have adequately evaluated the safety and efficacy of PRP treatments and concluded that PRP is "a promising, but not proven, treatment option for joint, tendon, ligament, and muscle injuries".
Proponents of PRP therapy argue that negative clinical results are associated with poor quality PRP produced by inadequate devices. The fact that most gathering devices capture a percentage of a given thrombocyte count is a bias, since there is significant inter-individual variability in the platelet concentration of human plasma. More is not necessarily better in this case. The variability in platelet concentrating techniques may alter platelet degranulation characteristics that could affect clinical outcomes.
. It is not clear if local injections of PRP can have a systemic impact on circulating cytokine levels, in turn affecting doping tests; it is also not clear whether PRP treatments have systemic anabolic effects or affect performance. In January 2011, the World Anti-Doping Agency 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".
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
that has been enriched with platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
s. As a concentrated source of autologous platelets, PRP contains (and releases through degranulation
Degranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
) several different growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
s and other cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s that stimulate healing of bone and soft tissue
Soft tissue
In anatomy, the term soft tissue refers to tissues that connect, support, or surround other structures and organs of the body, not being bone. Soft tissue includes tendons, ligaments, fascia, skin, fibrous tissues, fat, and synovial membranes , and muscles, nerves and blood vessels .It is sometimes...
.
Components
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 thrombinThrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
and calcium chloride
Calcium chloride
Calcium chloride, CaCl2, is a salt of calcium and chlorine. It behaves as a typical ionic halide, and is solid at room temperature. Common applications include brine for refrigeration plants, ice and dust control on roads, and desiccation...
, which induces the release of these factors from alpha granules
Platelet alpha-granule
In platelets, the term "alpha granules" is used to describe granules containing several growth factors.-Contents:Contents include insulin-like growth factor 1, platelet-derived growth factor, TGFβ, platelet factor 4 and other clotting proteins In platelets, the term "alpha granules" is used to...
. The growth factors and other cytokines present in PRP include:
- platelet-derived growth factorPlatelet-derived growth factorIn molecular biology, platelet-derived growth factor is one of the numerous growth factors, or proteins that regulate cell growth and division. In particular, it plays a significant role in blood vessel formation , the growth of blood vessels from already-existing blood vessel tissue. Uncontrolled...
- transforming growth factor beta
- fibroblast growth factorFibroblast growth factorFibroblast growth factors, or FGFs, are a family of growth factors involved in angiogenesis, wound healing, and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal...
- insulin-like growth factor 1Insulin-like growth factor 1Insulin-like growth factor 1 also known as somatomedin C is a protein that in humans is encoded by the IGF1 gene. IGF-1 has also been referred to as a "sulfation factor" and its effects were termed "nonsuppressible insulin-like activity" in the 1970s.IGF-1 is a hormone similar in molecular...
- insulin-like growth factor 2Insulin-like growth factor 2Insulin-like growth factor 2 is one of three protein hormones that share structural similarity to insulin.-Gene structure:In humans, the IGF2 gene is located on chromosome 11p15.5, a region which contains numerous imprinted genes. In mice this homologous region is found at distal chromosome 7...
- vascular endothelial growth factorVascular endothelial growth factorVascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....
- epidermal growth factorEpidermal growth factorEpidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR...
- Interleukin 8Interleukin 8Interleukin-8 is a chemokine produced by macrophages and other cell types such as epithelial cells. It is also synthesized by endothelial cells, which store IL-8 in their storage vesicles, the Weibel-Palade bodies...
- keratinocyte growth factorKeratinocyte Growth FactorThe Keratinocyte Growth Factor , 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....
- connective tissue growth factorCTGFCTGF is a cysteine-rich, matrix-associated, heparin-binding protein. In vitro, CTGF mirrors some of the effects of TGF beta on skin fibroblasts, such as stimulation of extracellular matrix production, chemotaxis, proliferation and integrin expression...
Preparation
There are, at present, two methods of PRP preparation approved by the U.S. Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
. Both processes involve the collection of whole blood
Whole blood
Whole blood is a term used in transfusion medicine for human blood from a standard blood donation. The blood is typically combined with an anticoagulant during the collection process, but is generally otherwise unprocessed...
that is anticoagulated
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
with citrate dextrose
Acid-citrate-dextrose
Acid Citrate Dextrose Solution is a solution of citric acid, sodium citrate and dextrose in water. It is mainly used as an anticoagulant to preserve blood specimens required for tissue typing, it is also used during procedures such as plasmapheresis instead of heparin...
) before undergoing two stages of centrifugation
Centrifugation
Centrifugation is a process that involves the use of the centrifugal force for the sedimentation of mixtures with a centrifuge, used in industry and in laboratory settings. More-dense components of the mixture migrate away from the axis of the centrifuge, while less-dense components of the mixture...
designed to separate the PRP aliquot from platelet-poor plasma and red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s. In humans, the typical baseline blood platelet count is approximately 200,000 per µL
Litre
pic|200px|right|thumb|One litre is equivalent to this cubeEach side is 10 cm1 litre water = 1 kilogram water The litre is a metric system unit of volume equal to 1 cubic decimetre , to 1,000 cubic centimetres , and to 1/1,000 cubic metre...
; therapeutic PRP concentrates the platelets by roughly five-fold. There is however broad variability in the production of PRP by various concentrating equipment and techniques.
Clinical applications
In humans, PRP has been investigated and used as clinical tool for several types of medical treatments, including nerve injuryNerve injury
Nerve injury is injury to nervous tissue. There is no single classification system that can describe all the many variations of nerve injury. Most systems attempt to correlate the degree of injury with symptoms, pathology and prognosis...
, tendinitis, cardiac muscle
Cardiac muscle
Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
injury, bone repair and regeneration, plastic surgery
Plastic surgery
Plastic surgery is a medical specialty concerned with the correction or restoration of form and function. Though cosmetic or aesthetic surgery is the best-known kind of plastic surgery, most plastic surgery is not cosmetic: plastic surgery includes many types of reconstructive surgery, hand...
, and oral surgery
Oral Surgery
Oral Surgery is a recognized international specialty in dentistry. It includes the diagnosis, surgical and related treatment of diseases, injuries and defects involving both the functional and esthetic aspects of the hard and soft tissues of the head, mouth, teeth, gums, jaws and neck.It involves,...
. PRP has also received attention in the popular media as a result of its use in treating sports injuries in professional athletes.
Clinical validity
The use and clinical validation of PRP is still in the early stages. Results of basic science and preclinical trialsPre-clinical development
In drug development, pre-clinical development is a stage of research that begins before clinical trials can begin, and during which important feasibility, iterative testing and drug safety data is collected....
have not yet been confirmed in large-scale controlled
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s. For example, clinical use of PRP for nerve injury and sports medicine has produced "promising" but "inconsistent" results in early trials. A 2009 systematic review
Systematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
of the scientific literature stated that there are few controlled
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s that have adequately evaluated the safety and efficacy of PRP treatments and concluded that PRP is "a promising, but not proven, treatment option for joint, tendon, ligament, and muscle injuries".
Proponents of PRP therapy argue that negative clinical results are associated with poor quality PRP produced by inadequate devices. The fact that most gathering devices capture a percentage of a given thrombocyte count is a bias, since there is significant inter-individual variability in the platelet concentration of human plasma. More is not necessarily better in this case. The variability in platelet concentrating techniques may alter platelet degranulation characteristics that could affect clinical outcomes.
Implications for doping
Some concern exists as to whether PRP treatments violate anti-doping rules, such as those maintained by the World Anti-Doping AgencyWorld Anti-Doping Agency
The World Anti-Doping Agency , , is an independent foundation created through a collective initiative led by the International Olympic Committee . It was set up on November 10, 1999 in Lausanne, Switzerland, as a result of what was called the "Declaration of Lausanne", to promote, coordinate and...
. It is not clear if local injections of PRP can have a systemic impact on circulating cytokine levels, in turn affecting doping tests; it is also not clear whether PRP treatments have systemic anabolic effects or affect performance. In January 2011, the World Anti-Doping Agency 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".