Thrombosis of a femoropopliteal vein graft as a complication of COVID-19 vaccination, with subsequent recanalization of the graft following gene therapy

Chronic limb-threatening ischemia (CLTI), formerly referred to as critical limb ischemia (CLI), is characterized by ischemic rest pain and tissue loss (ulceration or necrosis) in the presence of objectively documented arterial insufficiency, and is associated with a high risk of limb loss. We present the case of a 64-year-old male who developed right lower limb CLTI following iliac artery angioplasty. The patient was treated with surgical revascularization involving implantation of a femoropopliteal vein graft, followed by combined cell- and gene-based therapy comprising autologous bone marrow-derived CD34 + cells and a simultaneously administered VEGF165-encoding plasmid. This combined treatment allowed limb salvage and significant clinical improvement. However, ten years after surgery, the patient developed graft thrombosis temporally associated with COVID-19 vaccination, although a causal relationship could not be established. As the patient declined surgical reoperation, a second round of gene therapy was initiated, this time using a plasmid encoding VEGF, hepatocyte growth factor (HGF), and angiopoietin-1 (ANG-1). Gene therapy administered together with standard medical treatment was followed by gradual graft recanalization and clinical improvement of ischemic symptoms. This case represents a hypothesis-generating observation suggesting a potential role of angiogenic gene therapy as an adjunct to standard treatment strategies, including surgical revascularization and pharmacological therapy in patients with CLTI.