Autologous Platelet Lysate Product Versus Placebo in Patients with Chronic Leg Ulcerations: A Pilot Study Using a Randomized, Double-Blind, Placebo-Controlled Trial

Brent Weed; Mark D. P. Davis, MD; Cindy L. Felty, MSN, RN, CS; David A. Liedl, RN, RVT; Alvaro A. Pineda, MD; S. Breanndan Moore, MB, BCh, FRCPI; Thom W. Rooke, MD


Wounds. 2004;16(9) 

In This Article

Abstract and Introduction

The objective of the authors' study was to assess the ability of autologous platelet lysate factors to facilitate healing of chronic cutaneous ulcers. Twenty-six patients with chronic leg ulcers participated in this prospective, randomized, double-blind, placebo-controlled trial at the wound care center at a tertiary care institution. Fifteen patients received autologous platelet lysate product mixed with collagen (treatment group); 11 patients received platelet-poor plasma mixed with collagen (placebo group). Treatment was applied twice daily for 12 weeks. After a two-week washout period, patients whose ulcers had not healed were assigned to receive the other treatment for an additional 12 weeks. The principal end point was the occurrence of complete healing (100% epithelialization of the entire target ulcer) as assessed by ulcer photography and clinical examination. A secondary end point was the rate at which the wound healed. Demographic characteristics were similar in both groups. There was no significant difference between the treatment group and the placebo group as measured by area of the wounds and by the randomization strategy at baseline, Week 12 (end of the first treatment period), and Week 28 (end of the study period). The rate of healing was not significantly different between the treatment group and the placebo group. The median slope estimating the rate of healing over time was -0.79 for the treatment group and -0.84 for the placebo group. The addition of autologous platelet lysate product to collagen did not accelerate the rate of wound healing or significantly decrease wound size compared with platelet-poor plasma with collagen.

Platelet growth factors are intimately involved with wound healing.[1,2,3,4,5,6] Whether they are indispensable to wound healing is unclear, because naturally occurring growth factor deficiency states have not been identified.

Platelets contain at least five growth factors that may contribute to tissue formation and epithelialization: platelet-derived growth factor (PDGF), platelet factor 4, transforming growth factor-ß, platelet-derived angiogenesis factor, and platelet-derived epidermal growth factor. Each growth factor has several biological activities. The combination of PDGF, platelet-derived angiogenesis factor, transforming growth factor-ß, and possibly platelet-derived epidermal growth factor enhances granulation tissue growth while stimulating angiogenesis, fibroplasia, and extracellular matrix synthesis. Platelet factor 4 and PDGF attract neutrophils for host defense, and the combination of PDGF and platelet-derived epidermal growth factor stimulates epithelialization.

PDGF is an extraordinarily potent mitogen for most mesenchymally derived connective tissue-forming cells, such as fibroblasts, smooth muscle cells, and glial cells. It is also chemotactic for the same cells for which it is mitogenic, including neutrophils and monocytes. After monocytes enter the wound, they convert to macrophages, which in turn serve as additional growth factor sources. Exposure to PDGF brings about numerous intracellular events, including calcium mobilization, increased DNA synthesis leading to cell proliferation, increased expression of certain genes, and increased RNA synthesis leading to increased production of collagen, proteoglycans, and elastic fiber proteins by connective tissue-forming cells. Platelet factor 4 is released from the alpha granule locally in injured tissue during platelet activation; it binds heparin and is chemotactic for polymorphonuclear leukocytes and monocytes. Transforming growth factor-ß stimulates cell proliferation, protein synthesis, and collagen synthesis. It also inhibits growth of many epithelial tumor cells and fibroblastic cell lines. Platelet-derived angiogenesis factor is a polypeptide capable of stimulating new capillary growth by inducing migration of endothelial cells. Platelet-derived epithelial cell growth factor is partially responsible for the initial influx of neutrophils into the wound space; it is also a mitogen for many cells, including epithelial cells and fibroblasts. More recently, Herouy, et al.,[7] demonstrated that autologous platelet releasate containing these growth factors significantly increased protein expression of alphavbeta[3] integrin in leg ulcers. They suggested this as the mechanism by which platelet factors influence the process of angiogenesis and revascularization, thus promoting granulation tissue formation.

These platelet growth factors can be collected either by activating the platelets with thrombin, inducing them to release the factors (releasate), or by lysing the platelets (lysate). Previous studies have found that platelet product containing growth factors may accelerate wound healing;[8,9,10,11,12,13,14] however, some studies have not found efficacy on comparison with placebo.[15,16] Of four prospective, randomized, placebo-controlled, blinded studies, two showed efficacy,[8,9] and two did not[15,16] ( Table 1 and Table 2 ).

To assess the ability of autologous platelet lysate factors to facilitate the healing of chronic cutaneous ulcers, the authors conducted a prospective, randomized, double-blind, placebo-controlled trial in which the authors compared healing times for ulcers treated using autologous platelet lysate factors added to collagen (treatment group) with the healing times for ulcers treated with platelet-poor plasma plus collagen (placebo group).