Homocysteine Levels as a Potential Contributor to Impaired Wound Healing in Plastic and Reconstructive Surgery

Plastic and reconstructive surgery (PRS) relies heavily on dependable tissue perfusion. Though evidence supports the effect of homocysteine levels, including the presence of hyperhomocysteinemia (HHcy), on wound healing and flap thrombosis, it is typically not incorporated into perioperative risk assessment models. Homocysteine disrupts tissue healing by inducing endothelial dysfunction, generating reactive oxidative species, reducing nitric oxide availability, and impairing vasodilation. It also activates inflammatory signals and interferes with collagen cross-linking, a process necessary for wound strength. This is particularly important in PRS, where healing occurs across large reconstructive fields, including those that have been previously operated on or irradiated. PRS-specific data remain limited, as only one animal-model study has demonstrated that severe HHcy significantly increased flap necrosis rates, microangiography, and inflammatory infiltration, suggesting a direct impairment to tissue viability and repair. In microsurgical reconstruction, patients with underlying hypercoagulable states, including HHcy, demonstrated high rates of thrombotic complications and a complete lack of salvage once thrombosis occurred, suggesting that even moderate detriments to endothelial function and coagulation may cause significant flap compromise. The gap of homocysteine integration in PRS risk models is important due to its potential modifiability through factors such as folate and B-vitamin status. Homocysteine levels may offer an opportunity for perioperative optimization without added resource or significant cost burdens, and integrating it into assessment frameworks could provide a feasible opportunity to reduce wound healing complications among high-risk patients. Prospective trials are needed to evaluate this and whether the improvement of homocysteine levels enhances healing in complex reconstructive cases. Standardized clinical endpoints, including time to epithelialization, wound dehiscence, partial flap necrosis, and infection rates, should be documented. Flap-specific variables such as flap type, staged reconstruction, and anesthetic agents can also be evaluated, while patient factors such as albumin, diabetes, peripheral disease, and tobacco use should be controlled for.