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AHCPR Health Technology Reviews. Rockville (MD): Agency for Health Care Policy and Research (US); 1992-1995.

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This publication is provided for historical reference only and the information may be out of date.

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2Procuren: A Platelet-derived Wound Healing Formula

, MD, PhD and , MD.

Published: July 1992.

Report

This technical review examines safety efficacy of using Procuren, a platelet-derived wound-healing formula, for treating nonhealing wounds. A search of the literature and responses received from professionals who are involved in the study of growth factors, including platelet-derived growth factors, indicated that the data furnished to CHAMPUS by the proponents and forwarded to OHTA are representative of published studies on the use of platelet extracts for promotion of wound healing in human.(1-3). Another relevant publication was the recent study by Robson et al,(4). who described the potential ulcer-healing effects of a purified recombinant platelet-derived growth factor in a small number of patients.

Wound healing, consisting of an adequate inflammatory response and tissue repair, is essential for the maintenance and survival of multicellular organisms. Although there is abundant histological evidence that details the sequence of cellular events that are involved in the inflammatory and tissue repair responses to wounds, little is known about the precise mechanisms or the mediators that initiate and sustain these essential processes.(5-7). Platelets and other inflammatory cells that accumulate at the wound site would appear to be the sources of the postulated factors that direct the migration of cells into the wounds and orchestrate the repair processes.

Various proteins and growth factors that stimulate aspects of the healing process have been isolated from platelets. Two of these factors that are rapidly released after platelets are activated by thrombin have been identified as platelet-derived growth factor (PDGF) and transforming growth factor beta1 (TGF-beta(1)). Purified preparations of these factors have been made by recombinant DNA procedures and have been used to study their effects in cultured cell preparations and in animal models. These studies showed that PDGF and TGF-beta(1) are potent chemotaxins that recruit monocytes, macrophages, endothelial cells, and fibroblasts to the wound and stimulate the laying down of extracellular matrix, synthesis of collagen, and remodeling of collagen. In animals, the application of these recombinant DNA-derived growth factors to experimentally inflicted wounds has demonstrated that they are therapeutic vulnerary agents that accelerate normal wound repair and appear to reverse deficient repair. Recombinant human PDGF (rPDGF-BB) was shown to hasten the rate of healing of an experimental animal wound that resulted in a healed wound indistinguishable from an eventually healed, untreated wound.

Although the animal model studies have clearly shown that recombinant DNA-derived platelet growth factors are potent stimulators of the healing process, comparable studies in humans were not reported until the recent paper by Robson et al.(4). This publication described a study done in 20 patients who had pressure ulcers. The patients were randomly assigned to four goups, one serving as a placebo control group and the other three groups receiving three different dose applications of the rPDGF-BB. Although the authors stated that rPDGF-BB applied topically to chronic pressure ulcers may accelerate wound closure compared with that in a similarly managed placebo group, the observed results are not convincing because only the 5 patients receiving the highest dose of rPDGF-BB showed a possible improvement over the placebo group at a P value= .12. Mean volume of the ulcers at the end of 29 days of treatment in this group was reported to be 4.0 of the original mean volume, while that in the placebo group decreased to 5.6 of the original mean volume. The results indicated that all of the ulcers healed very well, regardless of the application of topical rPDGF-BB; patients treated with the lesser amounts of rPDGF-BB showed changes in ulcer volumes that were not significantly different from those in the placebo group.

The observations of Robson et al(4). suggest that the amount of rPDGF-BB may determine whether the factor influences the wound-healing process. In addition, the possibility arises that the effects on wound healing may not have been so apparent in Robson's study because of the absence of, and need for, other factors that are known to be released by platelets. Crude extracts of platelets, on the other hand, may contain a unique or "natural" combination of factors that may be needed to stimulate and direct the processes that result in the healing of wounds.

Since platelets are a source of proteins and growth factors that have potent wound-healing effects in animals, it would seem reasonable that extracts of platelets might have beneficial effects in wound healing. The observations reported by Knighton et al(1,2). and by Atri et al(3). appear to indicate that the application of crude extracts of platelets promotes the healing of chronic, nonhealing wounds. These reports are the only published accounts of the clinical use of crude platelet extracts for the promotion of wound healing. Besides the small number of patients in each study (32 in Knighton's study and 23 in Atri's study), important variables, such as the types of patients and the contents of the extracts, were not controlled or monitored, thus making the interpretation of the results very difficult. It would also seem that, under normal circumstances where wounds have access to platelets and inflammatory cells, the need for the application of platelet extracts to promote wound healing is not apparent unless the endogenous platelets do not carry sufficient growth factors to stimulate the healing processes. Furthermore, in order for the topically applied factors to stimulate wound healing, inflammatory cells must be delivered to the wound site via the circulation that normally would be expected to deliver platelets along with the other necessary types of cells.

In summary, besides two uncontrolled studies (one by Knighton et al(1). in 1986 and one by Atri et al(3). in 1990), the small controlled study by Knighton et al(2). in 1990 remains the only published account of the effect of the application of a platelet-derived wound-healing formula in patients with nonhealing wounds. The authors' statement that "the study sample was small and randomization was not stratified according to diagnostic groups" exemplifies the present lack of data upon which a decision might be made regarding the safety and efficacy of platelet-derived wound-healing formulas. While a role of platelets in wound healing has been suggested for many years, without sufficient published data it is possible to determine the clinical effectiveness of Procuren nor whether its use may be appropriate and acceptable medical practice.

The National Institutes of Health have been consulted, and they concur with the substance of this report. They further indicate that there are insufficient data to establish a benefit of platelet extract upon wound healing, and although limited information may suggest a salutary effect, further studies are needed.

References

1.
Knighton DR, Ciresi KF, Fiegel VD, et al. Classification and treatment of chronic nonhealing wounds: Successful treatment with autologous platelet-derived wound healing factors (PDWHF) Ann Surg. 1986;204:322–330. [PMC free article: PMC1251286] [PubMed: 3753059]
2.
Knighton DR, Ciresi K, Fiegel VD, et al. Stimulation of repair in chronic, nonhealing, cultaneous ulcers using platelet-derived wound healing formula. Surg Gynecol Obstet. 1990;170:56–60. [PubMed: 2403699]
3.
Atri SC, Misra J, Bisht D, Misra K. Use of homologous platelet factors in achieving total healing of recalcitrant skin ulcers. Surgery. 1990;108: 508–512. [PubMed: 2396195]
4.
Robson MC, Phillips LG, Thomason A, et al. Platelet-derived growth factor BB for the treatment of chronic pressure ulcers. Lancet. 1992;339:23–25. [PubMed: 1345953]
5.
Deuel TF, Kawahara RS, Mustoe TA, Pierce GF. Growth factors and wound healing: Platelet-derived growth factor as a model cytokine. Annu Rev Med. 1991;42:567–584. [PubMed: 2035994]
6.
Pierce GF, Vande Berg J, Rudolph R, et al. Platelet-derived growth factor-BB and transforming growth factor beta 1 selectively modulate glycosaminoglycans, collagen, and myofibroblasts in excisional wounds. Am J Pathol. 1991;138:629–646. [PMC free article: PMC1886289] [PubMed: 2000940]
7.
Pierce GF, Brown D, Munstoe TA. Quantitative analysis of inflammatory cell influx, procollagen type I synthesis, and collagen cross-linking in incisional wounds: Influence of PDGF-BB and TGF-beta 1 therapy. J Lab Clin Med. 1991;117:373–382. [PubMed: 2019792]

AHCPR Pub. No. 92-0065

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