Platelet-rich Plasma:

Properties and Clinical

Applications
RICK G. SMITH, B.S., C.C.P., CRAIG J. GASSMANN, C.C.P.,
AND MARK S. CAMPBELL, B.A., C.C.P.
Perfusion Management Group, Ltd., Lancaster, PA

ABSTRACT blood product, it carries no risk of transmitting infec-

Platelet-rich plasma (PRP) is an autologous product derived tious disease.
from whole blood through the process of gradient density
centrifugation. Autologous PRP has been shown to be safe PRP has an extremely broad range of clinical healing
and effective in promoting the natural processes of wound applications in head and neck surgery, otolaryngology,
healing, soft tissue reconstruction, and bone reconstruction cardiovascular surgery, burns and wound healing, oral
and augmentation. The potential value of PRP lies in its ability and maxillofacial surgery, cosmetic surgery, and peri-
to incorporate high concentrations of platelet-derived growth odontics (Table 1). In addition to its effectiveness for
factors, as well as fibrin, into the graft mixture. Recently patients with chronic non-healing wounds, it has also
published studies have demonstrated beneficial results with been used as an antiangiogenic agent and as a carrier for
PRP used in a broad range of clinical healing applications. growth factors.
PRP has been shown to increase the rate of bone maturation
and to improve bone density when added to small bony defects, In surgical settings, PRP decreases the frequency of
or to larger defects in combination with grafting material. intraoperative and postoperative bleeding at donor
Moreover, PRP can be exogenously applied to soft tissues and recipient sites, accelerates soft-tissue healing, sup-
to promote wound healing and tissue sealing. In patients ports the initial stability of grafted tissue at recipient
undergoing certain surgical procedures, perioperative use of sites as a result of its cohesive and adhesive nature,
PRP may decrease the length of hospitalization and the need promotes rapid vascularization of healing tissue by
for allogeneic blood products. PRP is a promising biotechnol- delivering growth factors and, when used in com-
ogy that is fueling growing interest in tissue engineering and bination with bone replacement materials, induces
cellular therapeutics. regeneration.

I. INTRODUCTION PRP vs. Fibrin Glue

Platelet-rich plasma (PRP) is an autologous product Use of PRP involves taking a sample of a patient’s blood
that concentrates a large number of platelets in a small preoperatively, concentrating autologous platelets by
volume of plasma.1,2 PRP functions as a fibrin tissue adhe- centrifugation, and after activating the platelets with
sive with hemostatic and tissue sealing properties, but thrombin and calcium, applying the resultant gel to the
it differs from fibrin glue and other platelet-poor tissue surgical site. This technique produces a blood clot in
adhesives because its platelets provide a unique ability to which platelets predominate in nearly a reverse ratio to
promote wound healing and enhance osteogenesis. red blood cells compared with a natural clot. Surgical
sites enhanced with PRP heal at rates two to three times
PRP provides an immediate surgical hemostatic agent those of untreated surgical sites.
that is biocompatible, safe, and effective. PRP acceler-
ates endothelial, epithelial, and epidermal regeneration, PRP must be distinguished from fibrin glues or seal-
stimulates angiogenesis, enhances collagen synthesis, ants, which have been used for many years as a surgical
promotes soft tissue healing, decreases dermal scarring, adjunct to promote local hemostasis at incision sites.
enhances the hemostatic response to injury, and reverses The important difference is the high concentration of
the inhibition of wound healing caused by glucocorti- platelets and the normal concentration of fibrinogen in
coids. The high leukocyte concentration of PRP has an PRP, whereas autologous fibrin glues or sealants can be
added antimicrobial effect. Since PRP is an autologous created from platelet-poor plasma and consist primarily

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 prp and wound healing

TABLE 1. MISCELLANEOUS CLINICAL APPLICATIONS FOR PRP.

Neurosurgery Augmentation & reduction mammoplasty

Pituitary tumor removal Reconstructions
Skull base tumor resection Urology
Intradural procedures involving tumor or release of Radical retro-pubic prostatectomy, & retroperitoneal
tethered cords lymph node dissections
Dural tumors
Periodontal Surgery
Acoustic neuroma excisions (dura tears during
Dental implants
laminectomy)
Guided Bone Regeneration
Oral and Maxillofacial Surgery
Orthopedic/Spinal Surgery
Mandibular reconstruction
Total Hip Replacement
Alveolar cleft repair
Total Knee Replacement
Oral-nasal fistulas
Scoliosis Repair
Otorhinolaryngology-Head and Neck Surgery Spinal Fusion
Radical neck dissections All Open and Internal Reduction Fixation
Pectoralis major myocutaneous flaps Operations
Facial fractures Hand and Foot Surgery
Reconstructions Bone Graft Surgery
Cosmetic Surgery Cardiothoracic Surgery
Full and split-thickness skin grafts donor sites and Sternotomy
recipient sites Graft Conduit Sites
Skin flaps Esophagogastrectomy
Bone grafts
General Surgery
Metal implants
Recurrent Hernia Repair
Tissue expansion
Anal Fistula
Aesthetic Surgery (Face Lifts, liposuction, etc)
Bariatric Surgery

of fibrinogen. (Commercial fibrin glues are created from enhances activation of platelets and the subsequent
pooled homologous human donors.) When PRP com- formation of a hemostatic plug which minimizes fur-
bined with thrombin and other activators such as calcium ther bleeding. Production of thrombin and activation
is used as an autologous formulation of fibrin glue, the of platelets also initiate the process of wound healing
high concentration of platelets promotes wound healing, via thrombin-dependent cell activation and platelet-
bone growth, and tissue sealing. dependent angiogenesis.3

II. MECHANISMS PRP mimics the last step of the coagulation cascade, the
Hemostatic Response to Injury formation of a fibrin clot. In vivo, the development of
The initial vascular response to injury includes the a primary hemostatic plug begins with the activation of
release of subendothelial factors that attract circulating platelet membrane receptors through which the adhesive
platelets and activate coagulation proteins. Platelets macromolecules von Willebrand factor and fibrinogen
respond by aggregating at, and adhering to, the site of anchor platelets to the vessel wall and link them to
injury, where they release granules containing serotonin, each other. A secondary hemostatic plug composed of
thromboxane, and adenosine, and initiate coagulation platelets enmeshed in fibrin, results from the action of
and the formation of fibrin. Local production of thrombin thrombin, which is essential for the formation of fibrin

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 prp and wound healing

TABLE 2. GROWTH FACTORS IN PLATELETS.

Growth Factor Primary Functions

Epidermal growth factor Regulation of cell proliferation, differentiation, and survival
Insulin-like growth factor Key regulator of cell metabolism and growth
Stimulates proliferation and differentiation functions in osteoblasts
Platelet-derived growth factor Major mitogen for connective tissue cells and certain other cell types.
Promotes the synthesis of collagen and structural proteins
Transforming growth factor (ie, alpha, beta) Regulation of cell proliferation, differentiation, and apoptosis
Induction of intimal thickening
Vascular endothelial growth factor Regulation of angiogenesis

and the activation of coagulation factors V and VIII. most are variations on a standard theme. Blood is drawn
The balance of all components—vessel wall, platelets, from the patient and fractionated using centrifugation.
adhesive proteins, coagulation factors, and regulatory The platelets are concentrated in the platelet rich plasma
mechanisms—determines the effectiveness of the hemo- at levels generally 6 to 8 times the baseline levels. The
static plug in maintaining the structural and functional resultant PRP is stored at room temperature until needed,
integrity of the vessel. at which time 10,000 units of powdered bovine thrombin
is mixed with 10% calcium chloride. Next, the PRP is
Growth Factors drawn into a 10ml syringe. The thrombin/calcium-
PRP exerts its beneficial effects via the degranulation of chloride mixture then is aspirated into a 1 ml syringe
the alpha granules in platelets that contain growth factors and both syringes are mounted in a mixing applicator.
believed to be important in early wound healing (Table 2). At the tip of the applicator, the two preparations are
When the platelets in PRP are activated by thrombin, mixed to activate the PRP. Within 5 to 30 seconds, a gel
they release growth factors and other substances that is formed as the citrate is neutralized and the thrombin
serve to accelerate the wound-healing process by increas- activates polymerization of the fibrin and degranulation
ing cellular proliferation, matrix formation, osteoid of the platelets. The gel then is inserted into the surgical
production, connective tissue healing, angiogenesis, and field as needed.
collagen synthesis.
Most current methods of PRP preparation use calcium
The active secretion of these growth factors begins and bovine thrombin to initiate formation of PRP
within minutes of the start of the coagulation sequence, gel. The use of bovine thrombin has unfortunately
and more than 90% are secreted during the first hour. been associated with the development of antibodies to
After this initial burst, the platelets synthesize and human clotting factors V, XI, and thrombin, resulting
secrete additional growth factors for the remaining in a risk of potentially life-threatening coagulopathies.
7 days of their viability. Macrophages then arrive due to Consequently, there is a growing interest in identify-
the vascular in-growth stimulated by the platelets and ing alternative agents for activation of PRP, such as
regulate wound-healing by secreting some of the same autologous human thrombin or synthetic peptides such
growth factors plus additional ones. The rate of wound as thrombin receptor agonist peptide-6.4
healing is determined by the number of platelets in the
blood clot within the graft or wound, and PRP increases Several commercial systems are available for prepar-
that initial number. ing PRP, including the Cobe Angel Whole Blood
Separation System which also can produce fibrin glue
Preparation (Cobe Cardiovascular, Inc., Arvada, Colorado) and the
Numerous techniques have been described for the imme- Sequire Platelet Concentrating System (PPAI Medical,
diate preoperative preparation of autologous PRP, but Fort Myers, Florida). Most commercial PRP preparation

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 prp and wound healing

systems are available for office use by dental practitioners, ability to induce new bone formation (osteoinduction)
podiatrists and wound care physicians. In comparison properties.
with previous methods that employed autotransfusion
devices, current automated systems have shorter prepara- In subantral sinus augmentation, the combination of
tion times and require substantially less blood volume. PRP and freeze-dried bone allograft (FDBA) has been
shown to improve the rate of bone formation compared
Clinically, PRP is routinely combined with bone substi- with FDBA and resorbable membrane.8 Biopsy specimens
tutes during oral and maxillofacial surgical procedures. obtained 4.5 to 6 months after the grafting procedure,
These include BioOss, an inorganic bovine bone substi- when implants were being inserted, revealed that sinuses
tute, AlloGro, demineralized freeze-dried human bone treated with FDBA and PRP had a significantly higher
allograft, and 45S5 BioGlass, a melt-derived bioactive percentage of vital tissue and bone than those treated
glass ceramic. with FDBA and membrane. Similarly, the relative
proportion of vital bone to residual graft particles was
III. PHYSIOLOGIC EFFECTS significantly greater with PRP.
Wound Healing
Human studies have shown that PRP can be advanta- CLINICAL STUDIES
geously and easily applied in surgery. Man and colleagues In addition to PRP’s use for reconstruction of soft tissue
used PRP in 20 patients undergoing cosmetic surgery, and bone in facial plastic and reconstructive surgery, a
including face lifts, breast augmentations, breast reduc- wide variety of applications elsewhere in the body has been
tions, and neck lifts. The application of PRP yielded reported. However, many reports are anecdotal and few
adequate hemostasis if platelet-poor plasma (PPP) was include controls. Despite a large variety of animal stud-
also applied to create a seal to halt bleeding, because ies, the findings are often conflicting, and the studies lack
PPP contains much higher amounts of fibrinogen. The standardization. Conclusions from comparisons between
authors reported that bleeding capillaries were effectively clinical and animal studies must be viewed with caution.
sealed within 3 minutes after application of PRP and
PPP. They also noted the added advantage that the use In one of the largest prospective, randomized, clinical tri-
of electrocautery could be minimized, thus decreasing the als of PRP, Everts and colleagues randomized 165 patients
risk of damage to adjacent nerves. They concluded that undergoing total knee arthroplasty to receive autologous
PRP offered significant benefits in terms of accelerated PRP and fibrin sealant applied on the wound at the end
wound healing and tissue repair. of surgery vs. standard surgical techniques.9 Patients in
the PRP group had a significantly higher post-operative
Bone Regeneration hemoglobin level (11.3 vs. 8.9 g/dl, respectively), and a
Platelets have been shown to stimulate the mitogenic decreased need for allogeneic blood products (0.17 vs.
activity of human trabecular bone cells and to increase 0.52 units, respectively) (P < 0.001). The incidences of
the proliferation rate of human osteoblast-like cells and wound leakage and wound healing disturbance were sig-
stromal stem cells, thus contributing to the regenera- nificantly less (P < 0.001) in patients managed with PRP
tion of mineralized tissues. Growth factors released from and fibrin sealant, and their hospital stay was decreased
platelets signal local mesenchymal and epithelial cells to by an average of 1.4 days (P < 0.001).
migrate, divide, and increase synthesis of collagen and
matrix, thus providing a scaffold that encourages migra- PRP has recently been shown to reduce the incidence of
tion of osteoblasts. Growth factors contained in PRP also sternal infections after cardiac surgery. Trowbridge and
stimulate chemotaxis, metabolism, and proliferation in colleagues compared a treatment group of 382 patients
osteoblasts and in bone marrow osteoprogenitor cells.6,7 who received PRP with a control group of 948 who did
not. The incidence of superficial infection was significantly
Guided bone regeneration is a standard surgical tech- lower in the treatment group (0.3% vs. 1.8%, p < .05). As
nique employed in implant dentistry to increase the for deep sternal wound infections, none were seen in the
quantity and quality of the host bone in areas of local- treatment group, versus 1.5% in the control group.10
ized alveolar defects. The unpredictability of osseous
regenerative procedures with various grafting materials The beneficial effects of treatment with PRP in patients
suggests that it would be highly desirable to improve their with chronic cutaneous wounds have been inconsistent.

76 The Journal of Lancaster General Hospital • Summer 2007 • Vol. 2 – No. 2

 prp and wound healing

Margolis et al. reported that diabetic neuropathic foot CONCLUSIONS

ulcers treated with PRP were 14–59% more likely to Autologous PRP is a relatively new biotechnology that
heal than those treated with standard care.11 The ben- has shown promise in the stimulation and acceleration
eficial effects of PRP were greatest in patients with the of soft-tissue and bone healing. The efficacy of this
most severe wounds, i.e., large wounds affecting deeper treatment lies in the local delivery of a wide range of
anatomical structures. In contrast, Senet et al observed growth factors and proteins, mimicking and supporting
no beneficial effects of adjuvant treatment with PRP on physiologic wound healing and reparative tissue pro-
wound healing in a randomized, double-blind, placebo- cesses. Consequently, the application of PRP has been
controlled study of 15 patients with chronic venous extended to many different fields, including orthopedics,
leg ulcers.12 Wound fluid growth factor levels were not sports injuries, dental and periodontal surgery, and cos-
modified by treatment with PRP. metic, plastic, cardiovascular, general and maxillofacial
surgery.
Contraindications
Treatment with autologous PRP is generally considered Few well-designed scientific studies of the clinical use of
safe in appropriately selected patients. Potential can- PRP are available, and the optimal roles of PRP remain
didates for treatment with PRP should undergo a pre- undefined. The exact mechanisms of action of the many
treatment hematologic evaluation to rule out potential components of PRP are not fully understood, and the
coagulopathies and disorders of platelet function. Patients ideal ratios of these components are unknown. In some
who are anemic and those with thrombocytopenia may circumstances, the costs of implementing this promising
be unsuitable candidates for treatment with PRP. Other technology must be weighed against its benefits, and
potential contraindications include hemodynamic insta- well-designed controlled clinical studies are needed to
bility, severe hypovolemia, unstable angina, sepsis, and provide clear evidence of the capacity of PRP to improve
anticoagulant or fibrinolytic drug therapy. patient outcomes.

REFERENCES
1. Everts PA, Knape JT, Weibrich G, et al. Platelet-rich plasma and Tissue Engineering: Applications in Maxillofacial Surgery and Peridontics.
platelet gel: a review. J Extra Corpor Technol 2006;38:174-187. Chicago: Quintessence Publishing Co, Inc.; 1999; 71-82.

2. Marx RE. Platelet-rich plasma: Evidence to support its use. J Oral 8. Kassolis JD, Reynolds MA. Evaluation of the adjunctive benefits
Maxillofac Surg 2004; 62:489-496. of platelet-rich plasma in subantral sinus augmentation. J Craniofac Surg
2005;16:280-287.
3. Knighton DR, Hunt TK, Thrakral KK, Goodson WH. Role of plate-
lets and fibrin in the healing sequence. Ann Surg 1982;196:379-388. 9. Everts PA, Devilee RJ, Brown Mahoney C, et al. Platelet gel and fibrin
sealant reduce allogeneic blood transfusions in total knee arthroplasty. Acta
4. Landesberg R, Burke A, Pinsky D, et al. Activation of platelet-rich Anaesthesiol Scand 2006 May;50(5):593-9.
plasma using thrombin receptor agonist peptide. J Oral Maxillofac Surg
2005;63:529-535. 10. Trowbridge CC, Stammers AH, Woods E, et al. Use of platelet gel
and its effects on infection in cardiac surgery. JECT 2005; 37:381-386.
5. Man D, Plosker H, Winland-Brown JE. The use of autologous plate-
let-rich plasma (platelet gel) and autologous platelet-poor plasma (fibrin 11. Margolis DJ, Kantor J, Santanna J, et al. Effectiveness of platelet
glue) in cosmetic surgery. Plast Reconstr Surg 2001;107:229-237. releasate for the treatment of diabetic neuropathic foot ulcers. Diabetes
Care 2001;24:483-488.
6. Lind M. Growth factor stimulation of bone healing. Effects on
osteoblasts, osteomies, and implants fixation. ACTA Orthop Scand 1998; 12. Senet P, Bon FX, Benbunan M, et al. Randomized trial and local
283:2-37. biological effect of autologous platelets used as adjuvant therapy for chronic
venous leg ulcers. J Vasc Surg 2003;38:1342-1348.
7. Marx RE. Platelet-Rich Plasma: A Source of Multiple Autologous
Growth Factors for Bone Grafts. In: Lynch SE, Genco RJ, Marx RE, eds.

The Journal of Lancaster General Hospital • Summer 2007 • Vol. 2 – No. 2 77

 prp and wound healing

Rick G. Smith, B.S., C.C.P. Mark S. Campbell, B.A., C.C.P.

Clinical Perfusionist Clinical Perfusionist
[email protected] [email protected]

Craig J. Gassmann, C.C.P. Perfusion Management Group, Ltd.

Clinical Perfusionist P.O. Box 8257, Lancaster, PA 17604
[email protected] 717-544-5224

Mezquita (Mosque turned into Cathedral), Cordoba, Spain

Edward T. Chory, M.D.

78 The Journal of Lancaster General Hospital • Summer 2007 • Vol. 2 – No. 2