WHAT IS PLATELET RICH PLASMA

Introduction

The use of biologic therapy in the treatment of various musculoskeletal pathologies has increased
significantly over the last 10 years. Specifically, platelet-rich plasma (PRP) has been an increasingly
popular treatment for clinicians, especially for its potential in treating tendinopathy and degenerative
cellular diseases. The history of PRP in the clinical setting began as early as the 1980s when it was found
to be effective in blood loss during cardiac surgery . Its effect on bone was then examined in the field of
dentistry for its regenerative properties on bone maturation and formation. In time, its use in
musculoskeletal medicine has grown, and its role in tendon and tissue healing has been heavily
investigated [5].

History of Platelet-Rich Plasma

Platelet-rich plasma (PRP) is also known as platelet-rich growth factors (GFs), platelet-rich fibrin (PRF)
matrix, PRF, and platelet concentrate.
The concept and description of PRP started in the field of hematology [1]. Hematologists created the
term PRP in the 1970s in order to describe the plasma with a platelet count above that of peripheral
blood, which was initially used as a transfusion product to treat patients with thrombocytopenia [2].
Ten years later, PRP started to be used in maxillofacial surgery as PRF. Fibrin had the potential for
adherence and homeostatic properties, and PRP with its anti-inflammatory characteristics stimulated
cell proliferation.

Subsequently, PRP has been used predominantly in the musculoskeletal field in sports injuries. With its
use in professional sportspersons, it has attracted widespread attention in the media and has been
extensively used in this field. Other medical fields that also use PRP are cardiac surgery, pediatric
surgery, gynecology, urology, plastic surgery, and ophthalmology.
More recently, the interest in the application of PRP in dermatology; i.e., in tissue regeneration, wound
healing, scar revision, skin rejuvenating effects, and alopecia, has increased
Wounds have a proinflammatory biochemical environment that impairs healing in chronic ulcers. In
addition, it is characterized by a high protease activity, which decreases the effective GF concentration.
PRP is used as an interesting alternative treatment for recalcitrant wounds because it is a source of GFs
and consequently has mitogenic, angiogenic, and chemotactic properties.

In cosmetic dermatology, a study performed in vitro demonstrated that PRP can stimulate human
dermal fibroblast proliferation and increase type I collagen synthesis. Additionally, based on histological
evidence, PRP injected in human deep dermis and immediate subdermis induces soft-tissue
augmentation, activation of fibroblasts, and new collagen deposition, as well as new blood vessels and
adipose tissue formation.

Another application of PRP is the improvement of burn scars, postsurgical scars, and acne scars.
According to the few articles available, PRP alone or in combination with other techniques seems to
improve the quality of the skin and leads to an increase in collagen and elastic fibers.
In 2006, PRP has started to be considered a potential therapeutic tool for promoting hair growth and
has been postulated as a new therapy for alopecia, in both androgenetic alopecia and alopecia areata.
Several studies have been published that refer to the positive effect PRP has on androgenetic alopecia,
although a recent meta-analysis suggested the lack of randomized controlled trials. As stated by the
authors, controlled clinical trials are considered the best way to provide scientific evidence for a
treatment and avoid potential bias when assessing efficacy.
Platelet Biology

All blood cells derive from a common pluripotent stem cell, which differentiates into different cell lines.
Each of these cell series contains precursors that can divide and mature.
Platelets, also called thrombocytes, develop from the bone marrow. Platelets are nucleated, discoid
cellular elements with different sizes and a density of approximately 2 μm in diameter, the smallest
density of all blood cells. The physiological count of platelets circulating in the blood stream ranges from
150,000 to 400,000 platelets per μL.

Platelets contain several secretory granules that are crucial to platelet function. There are 3 types of
granules: dense granules, o-granules, and lysosomes. In each platelet there are approximately 50-80
granules, the most abundant of the 3 types of granules.

Platelets are primarily responsible for the aggregation process. The main function is to contribute to
homeostasis trough 3 processes: adhesion, activation, and aggregation. During a vascular lesion,
platelets are activated, and their granules release factors that promote coagulation .
Platelets were thought to have only hemostatic activity, although in recent years, scientific research and
technology has provided a new perspective on platelets and their functions. Studies suggest that
platelets contain an abundance of GFs and cytokines that can affect inflammation, angiogenesis, stem
cell migration, and cell proliferation.

PRP is a natural source of signaling molecules, and upon activation of platelets in PRP, the P-granules are
degranulated and release the GFs and cytokines that will modify the pericellular microenvironment.
Some of the most important GFs released by platelets in PRP include vascular endothelial GF, fibroblast
GF (FGF), platelet-derived GF, epidermal GF, hepatocyte GF, insulin-like GF 1, 2 (IGF-1, IGF-2), matrix
metalloproteinases 2, 9, and interleukin 8.

Definition

PRP is a biological product defined as a portion of the plasma fraction of autologous blood with a
platelet concentration above the baseline (before centrifugation). As such, PRP contains not only a high
level of platelets but also the full complement of clotting factors, the latter typically remaining at their

normal, physiologic levels. It is enriched by a range of GFs, chemokines, cytokines, and other plasma
proteins.

The PRP is obtained from the blood of patients before centrifugation. After centrifugation and according
to their different density gradients, the separation of blood components (red blood cells, PRP, and
platelet-poor plasma [PPP]) follows.
In PRP, besides the higher concentration of platelets, other parameters need to be taken into account,
such as the presence or absence of leucocytes and activation. This will define the type of PRP used in
different pathologies.

There are several commercial devices available, which simplify the preparation of PRP. According to the
manufacturers, PRP devices usually achieve a concentration of PRP 2-5 times the baseline concentration.
Although one might think that a higher platelet count with a higher number of GFs would lead to better
results, this has not been determined yet. Concentration of PRP 2.5 times above the baseline could have
an inhibitory effect.

Major factors in platelet-rich plasma

Platelets play an important role in healing at the site of injury. The increased number of platelets results
in increased number of secreted growth factors, thereby increasing the healing process. This
phenomenon is attributed as it promotes mitogenesis of healing capable cells and angiogenesis in the
tissues. Along with the presence of growth factors, they also contain adhesion molecules that include
fibrin, fibronectin and vitronectin which help promote bone formation.P RP preparations also play a role
in revascularization of damaged tissue by promoting cell migration, proliferation, differentiation and
stabilization of endothelial cells in new blood vessels. PRP also restores damaged connective tissue by
promoting the migration, proliferation and activation of fibroblasts. Platelets also host a vast reservoir
of over 800 proteins which when secreted act upon SCs, fibroblasts, osteoblasts and endothelial and
epithelial cells. The main purpose of using PRP for therapeutics originated from the idea to deliver the
growth factors, cytokines and α-granules to the site of injury, which acts as cell cycle regulators, and
promote healing process across variety of tissues.

The PRP preparations are known to contain many growth factors, chemokines and cytokines which
induce the downstream signaling pathways that ultimately lead to synthesis of proteins necessary for
collagen, osteoid and extracellular matrix formation. PRP also has numerous cell adhesion molecules
including fibrin, fibronectin, vitronectin and thrombospondin that trigger the assimilation of osteoblasts,
fibroblasts and epithelial cells. Apart from its role in structural and functional healing, PRP preparations
are also been implicated in the reduced use of narcotics, improved sleep and reduction in pain
perception.

Classification

Several authors have tried to characterize and classify the numerous techniques available on the market
in terms of preparation (centrifugation speed and use of anticoagulant), content (platelets, leucocytes,
and GFs), and applications.
Although the literature about PRPs developed with all these contradictions, the need for a standardized
terminology is of great importance. Thus, some classifications have been proposed to achieve a
consensus terminology in the field of platelet concentrates.
Characterizing the type of PRP used (as a pure PRPin our study) will lead to a better understanding of
PRP, and data available will be easier to sort and interpret. Furthermore, this terminology would serve
as a basis for further research on the topic.
In 2009, Dohan Ehrenfest et al. proposed a classification of 4 main families of preparations following 2
principle parameters: presence or absence of a cell content (such as leucocytes) and the fibrin
architecture:

1. Pure PRP or leucocyte-poor PRP: the preparation obtained is without leucocytes and shows a low-
density fibrin network after activation.
2. Leucocyte and PRP: the preparations contain leucocytes and show a low-density fibrin network after
activation.
3. Pure PRF or leucocyte-poor PRF: preparations are without leucocytes and with a high-density fibrin
network. Unlike pure PRP or PRP containing leukocytes, these products cannot be injected and exist in
an activated gel form.
4. Leucocyte-rich fibrin and PRF: products are preparations with leucocytes and with a high-density
fibrin network.
Another classification based on the presence or absence of white blood cells, activation status, and
platelet concentration, based on the coefficients of an increase in the platelet and leukocyte
concentration in PRP compared to the whole-blood baseline, as well as on PRP activation.
The classifications were not consensual and there is still the intent to search a classification for PRP that
could characterize the injected PRP in order to compare the efficacy of different studies.
An important point of discussion is that in the previous classifications, the authors did not take into
account the final volume of the preparation, the presence or absence of red blood cells (RBCs) in PRP,
and the doses of platelets in the final volume of PRP obtained.
In 2016 the DEPA classification (Dose, Efficiency, Purity, Activation) that focuses on the quantity of
platelets obtained by the PRP kits as well as on product purity and on platelet activation prior to
injection.
The DEPA classification is based on 4 different components:
1. Dose of injected platelets: calculated by multiplying the platelet concentration in PRP by the obtained
volume of PRP. According to the injected dose (measured in billions or millions of platelets), it should be
categorized into (a) very high dose of injected platelets of >5 billion; (b) high dose of injected platelets,
from 3 to 5 billion; (c) medium dose of injected platelets, from 1 to 3 billion, and (d) low dose of injected
platelets, <1 billion.
2. Efficiency of the production: corresponds to the percentage of platelets recovered in the PRP from
the blood. It is categorized as follows: (a) high device efficiency, if the recovery rate in platelets is >90%;
(b) medium device efficiency, if the recovery rate in platelets is between 70 and 90%; (c) low device
efficiency, if the recovery rate is between 30 and 70%, and (d) poor device efficiency, if the recovery rate
is <30% and corresponds to the relative composition of platelets, leucocytes, and RBCs in the obtained
PRP.
3. Purity of the PRP obtained: correlates to the relative composition of platelets, leucocytes, and RBCs in
the obtained PRP. It is described as (a) very pure PRP, if the percentage of platelets in the PRP,
compared with RBCs and leucocytes, is >90%; (b) pure PRP, between 70 and 90% of the platelets; (c)
heterogeneous PRP, if the percentage of platelets is between 30 and 70%, and (d) whole-blood PRP, if
the percentage of platelets in the PRP is <30% compared with RBCs and leucocytes.

4. Activation process: if an exogenous clotting factor was used to activate platelets, such as autologous
thrombin or calcium chloride.
Although this last classification is very complete, this quantification cannot be defined by the physician
and should be registered in each CE medical device available for preparation of PRP.

Conclusion
PRP is being used as a new therapeutic option for different pathologies in the field of dermatology, such
as trichology, wound healing, and cosmetic medicine. In this manner, understanding the biology and
mechanism of action of this therapy should help clinicians in selecting a system that meets their specific
needs for a given indication. In addition, characterizing the type of PRP used will lead to a
standardization of PRP, making it easier to sort and interpret available data. We hope that this review
serves as a basis for further research on the use of PRP.

REFERENCES:
1. Platelet-Rich Plasma: Review of Current Literature on its Use for Tendon and Ligament
Pathology Cameron Kia et al. University of Connecticut Health Center, 263 Farmington Ave,
Farmington, CT USA. 2018 Dec.
2. Alves R, Grimalt R: A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and
Classification. Skin Appendage Disord 2018;4:18-24. doi: 10.1159/000477353
3. Ramaswamy Reddy SH, Reddy R, Babu N C, Ashok G N. Stem-cell therapy and platelet-rich
plasma in regenerative medicines: A review on pros and cons of the technologies. J Oral
Maxillofac Pathol 2018;22:367-74

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