Activated protein C to heal pressure ulcers

Abstract

Pressure ulcers present a major clinical challenge, are physically debilitating and place the patient at risk of serious comorbidities such as septic shock. Recombinant human activated protein C (APC) is an anticoagulant with anti-inflammatory, cytoprotective and angiogenic effects that promote rapid wound healing. Topical negative pressure wound therapy (TNP) has become widely used as a treatment modality in wounds although its efficacy has not been proven through randomised controlled trials. The aim of this study was to determine the preliminary efficacy and safety of treatment with APC for severe chronic pressure sores with and without TNP. This case presentation describes the history, management and outcome of two patients each with a severe chronic non-healing pressure ulcer that had failed to respond to conventional therapy. TNP was added to conservative management of both ulcers with no improvement seen. Then local application of small doses of APC was added to TNP and with conservative management, resulted in significant clinical improvement and rapid healing of both ulcers, displaying rapid growth of vascular granulation tissue with subsequent epithelialisation. Patients tolerated the treatment well and improvements suggested by long-term follow-up were provided. Randomised placebo-controlled double blind trials are needed to quantify the efficacy, safety, cost-effectiveness, optimal dose and quality of life changes seen from treatment with APC.

Activated Protein C in Cutaneous Wound Healing: From Bench to Bedside

“…They also reported reduced patient stress scores following APC treatment, as assessed by the Cardiff Wound Impact Questionnaire, demonstrating improved quality of life. Two further case series have been published, each involving two patients, determining the efficacy of APC for ulcers caused by pyoderma gangrenosum in one study, and severe chronic pressure sores in the other [76,77]. APC was injected subcutaneously and applied topically combined with TNP, respectively; both methods led to clinical improvements and reductions in wound size (Figure 4).…”

Targeting PAR1: Now What?

“…Several case reports and small series suggest efficacy of APC in chronic skin ulcers in human subjects [98– 101]. In one study, 12 diabetic patients with non-healing ulcers were randomized to either topical APC or saline for 20 weeks [101].…”

A Critical Update of the Assessment and Acute Management of Patients with Severe Burns

“…62 Following tissue injury, APC modulates the inflammatory response through intracellular signaling mechanisms, 62,64,65 and in wounds it promotes controlled angiogenesis, [66][67][68][69] and stimulates reepithelialization. [70][71][72] This assists with the natural growth of well-vascularized granulation tissue from the base of the wound. It also facilitates cytoprotection through prevention of apoptosis and reduced inflammatory cell migration, which stabilizes the local cellular environment thus allowing and promoting the subsequent rapid growth of healthy new epithelium.…”