Erythropoietin and Soft Tissue Flap Survival: A Systematic Review

Area of Science:

• Regenerative Medicine
• Surgical Innovation
• Pharmacological Therapeutics

Background:

• Erythropoietin (EPO) exhibits tissue-protective properties, including anti-apoptotic, anti-inflammatory, and pro-angiogenic effects.
• Surgical flap necrosis is a significant challenge in reconstructive surgery, with limited success of current pharmacological agents.
• Novel therapeutic strategies are needed to improve surgical flap survival.

Purpose of the Study:

• To systematically review the efficacy of Erythropoietin (EPO) in improving surgical flap survival.
• To evaluate the impact of EPO on flap necrosis, perfusion, and molecular parameters in experimental models.
• To assess the safety profile of EPO in the context of reconstructive surgery.

Main Methods:

• A systematic review adhering to PRISMA guidelines was performed.
• Searches were conducted across PubMed, Embase, and CENTRAL databases up to September 2025.
• Included studies investigated EPO's effect on flap survival in animal or human models compared to placebo, analyzing flap necrosis and secondary outcomes.

Main Results:

• Nine animal studies involving various flap models (n=335) were analyzed.
• Erythropoietin (EPO) significantly reduced flap necrosis compared to controls.
• Optimal benefits were observed with short-course, low-dose peri-operative EPO administration, improving perfusion and microvasculature without reported safety concerns.

Conclusions:

• Erythropoietin (EPO) demonstrates efficacy in improving flap survival in experimental settings.
• Short-term, low-dose EPO preconditioning is the most effective strategy, while higher doses may pose risks.
• Further research, including clinical trials, is necessary to optimize EPO dosing for clinical application.