Description of the condition
A wound is an interruption of the integrity and continuity of the structures that comprise a tissue or organ, and may affect only the epidermis or go through deeper structures such as the dermis, subcutaneous tissue, fascia and even muscle and bone (Enoch 2008). These injuries usually result from external causes and surgical wounds are among the most common (Appendix 1). One study has estimated that 234 million major surgical procedures are undertaken every year worldwide (Weiser 2008).
Most surgical wounds are closed by primary intention (wound edges brought together and closed at time of surgery), but they can close by secondary intention (wound left open after surgery and allowed to heal with scar tissue replacing the tissue defect) or tertiary intention (wound left open after surgery, but later wound edges brought together and wound closed, also called delayed primary closure) (Sussman 2007).
The usual process of wound healing, including the healing of surgical wounds, takes place in four phases that subtly overlap: haemostasis (Appendix 1), inflammation, cell multiplication or proliferation, and remodeling of the new tissue to preserve the initial structure (Nguyen 2009). Damage to the blood vessels causes blood loss at the wound bed. Platelets aggregate along the cells of the injured vascular wall (endothelial cells) and release substances to form a clot rich in fibrin that fosters early wound closing (Appendix 1). Platelets that store various growth factor proteins, such as platelet-derived growth factor (PDGF), epidermal growth factor, vascular endothelial growth factor, and transforming growth factor beta (TGF), are called alpha granules. These growth factors are needed to promote the inflammatory and proliferative phases of wound healing. PDGF initiates the movement to the wound of inflammatory cells such as neutrophils and macrophages that act phagocytically to engulf bacteria and damaged tissue. PDF and TGF also stimulate other reparative cells such as fibroblasts and endothelial cells. Once debris has been removed, fibroblasts and endothelial cells start the proliferative phase. During the remodeling phase, excess matrix materials are removed, collagen fibres are cross-linked, and the wound contracts. Since platelets contain 100 times greater concentrations of many of the proteins liberated during the healing process than other tissues, they can be considered to be the true activators of wound healing.
Several factors can delay wound healing. Some are unchangeable, such as age and chronic systemic (whole body) conditions such as diabetes, ischaemia (lack of oxygen), infection or tissue necrosis (tissue death) (Menke 2007). In elective surgery, the risk of infection is mainly conditioned by the local environment of the site of incision. Depending on the incision site and the risk of infection, surgical wounds are classified as clean (class I), clean-contaminated (class II), contaminated (class III), dirty-infected (class IV), or unclassified (Berard 1964; Garner 1986; Simmons 1982) (see Table 1). Clean surgical procedures have lower infection rates than those classified as dirty, where infection rates can be above 30% (McLaws 2000). The Centers for Disease Control and Prevention (CDC) classified surgical site infection (SSI) as superficial incisional (skin and subcutaneous tissue), deep incisional (muscle and fascia) and organ/space (Horan 1992). The Coello 2005 study showed that the incidence of SSI in 140 English hospitals was 4.2%, and that superficial incisional SSI accounted for more than half of all SSIs. The cost attributable to SSI ranged from GBP 959 to GBP 6103 per patient (Coello 2005). Other studies have estimated an attributable mortality to SSI that ranges from 0.64% (Martone 1998), to 0.9% (Astagneau 2001). It is, therefore, clear that measures are needed to shorten healing time and facilitate the healing of the surgical wound.
Description of the intervention
Although there is a physiological platelet response to tissue injury, several techniques have been proposed to increase the number of platelets reaching the wound site in order to accelerate the healing process. One of these techniques is the use of autologous platelet-rich plasma (PRP) (Appendix 1). Autologous PRP is a product that contains a high concentration of platelets and is derived from the patient´s own fresh whole blood. The quantity of blood needed depends upon the area of the wound, and can range from 55 mL to 450 mL of whole blood in order to obtain between 5 mL and 50 mL of PRP (Khalafi 2008; Powell 2001). It has been postulated that the optimal concentration of PRP platelet count is 1 million/µL (Marx 2004). Preparation of PRP takes about 15 to 20 minutes and is usually done during surgery (Khalafi 2008).
There is no consensus about the use of a specific procedure to obtain a high concentrate of platelets or PRP. However, the procedure used to obtain platelets from the blood affects their volume and concentrates (O'Neill 2001). High concentrates of platelets are obtained with the use of apheresis devices that remove platelets from the blood (O'Neill 2001; Zimmermann 2008). The most common technique involves the use of a centrifuge to separate a concentrate of platelets from a blood sample obtained from the patient. The centrifuge speed and the number of times the blood is centrifuged can influence the final concentrate of platelets (O'Neill 2001). Several centrifuge device systems are available on the market, such as Plateltex®, PRGF®, Curasan®, PCCS®, Harvest®, Vivostat®, Regen® and Fibrinet®; there is little difference between them in relation to the platelet concentrate obtained (Leitner 2006; Mazzuco 2008; Schaaf 2008).
Once the platelet concentrate is obtained, its biologically-active content needs to be released. There are two methods for this: the first is to add thrombin or calcium, which activates platelet-release of the growth factors, to form platelet releasate (Appendix 1). The second approach is to induce physical lysis (breakdown) of the platelets, producing lysate (Appendix 1) by freezing (Weed 2004), or other methods, such as ultrasound (non-audible sound waves), that disrupt cell membranes and release cellular contents (Stacey 2000). The final product is applied locally to the wound as a gel or a solution.
The ease with which the autologous PRP can be obtained and its potential efficacy may make it cheaper than other options such as the recombinant human platelet-derived growth factors. One study showed PRP gel was cost-effective compared with other therapies for non-healing diabetic foot ulcers. The average five-year direct wound care costs per patient were USD 15,159 for patients treated with PRP gel compared to USD 40,073 for standard care, and USD 47,252 for those receiving recombinant human platelet-derived growth factor BB (Dougherty 2008). We did not find any studies about the cost of PRP in treating surgical wounds.
How the intervention might work
PRP is used to stimulate the regeneration of damaged tissue and accelerate the process of healing. It contains fibrin (Appendix 1) and high concentrations of growth factors that promote and accelerate both healing (Marlovits 2004), and tissue regeneration (Knighton 1988; Munirah 2007; Robinson 1993).
PRP could be useful in surgical wounds that are at risk of delayed healing and are difficult to cure adequately. PRP could accelerate the healing, shorten the hospital stay and reduce health costs. Shortening healing is important in complex interventions such as coronary bypass, where the surgery is traumatic (Khalafi 2008), or in wounds that heal by secondary intention, such as pilonidal abscesses (Spiridakis 2009). In other surgeries, such as plastic surgery, PRP could improve integrity of the tissue and minimize scarring (Powell 2001). For this reason, PRP is an emerging treatment in tissue engineering and cellular therapy (Bertoldi 2009). Autologous PRP has the added advantage that it poses a low, or null, risk of transmissible diseases or immune reactions.
Why it is important to do this review
The use of autologous PRP is increasing in surgical interventions. It is, therefore, important to examine the research evidence behind this technology thoroughly to determine risks and benefits. Many clinical trials are currently assessing PRP treatment. Most are conducted in the field of traumatology - in bone, muscle and tendon injuries - but others are also underway in other surgical pathologies such as pilonidal abscesses.
Two Cochrane systematic reviews (one assessing PRP in orthopaedic surgery for long bone healing (Griffin 2012), and one evaluating maxillofacial surgery for augmentation procedures of the maxillary sinus (Esposito 2010)), and a recently published meta-analysis assessing PRP for orthopaedic indications (Sheth 2012), revealed uncertainty about the efficacy of PRP. This uncertainty calls the increasing use of PRP into question. In another (non-Cochrane) systematic review that assessed PRP in patients with chronic and acute cutaneous wounds in a small number of primary studies, the percentage of wound infection and pain scores decreased in PRP-treated acute wounds, but the result was not statistically significant (Carter 2011). Carter 2011 focused only in studies that assessed PRP produced by a process of platelet activation (with thrombin or calcium), but it excluded studies that used other methods to obtain PRP like physical lyses of the platelets. Our inclusion criteria differ of the Carter 2011 because we will include studies that assess autologous PRP produced by any techniques in patient with surgical wounds. We will exclude studies in orthopaedic or maxillary surgery to avoid overlap with existing Cochrane systematic reviews.