Metabolic phenotyping in venous disease: The need for standardization

Venous thromboembolism (VTE), chronic venous disease (CVD), and venous leg ulceration (VLU) are clinical manifestations of a poorly functioning venous system. Though common, much is unknown of the pathophysiology and progression of these conditions. Metabolic phenotyping has been employed to explore mechanistic pathways involved in venous disease. A systematic literature review was performed: full text, primary research articles on the applications of nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) in human participants and animals were included for qualitative synthesis. Seventeen studies applying metabolic phenotyping to venous disease were identified: six on CVD, two on VLU, and nine on VTE; both animal (n = 6) and human (n = 10) experimental designs were reported, with one study including both. NMR, MS, and MS imaging were employed to characterize serum, plasma, urine, wound fluid, and tissue. Metabolites found to be upregulated in CVD included lipids, branched chain amino acids (BCAA), glutamate, taurine, lactate, and myo-inositol identified in vein tissue. Upregulated metabolites in VLU included lactate, BCAA, lysine, 3-hydroxybutyrate, and glutamate identified in wound fluid and ulcer biopsies. VTE cases were associated with reduced carnitine levels, upregulated aromatic amino acids, 3-hydroxybutyrate, BCAA, and lipids in plasma, serum, thrombus, and vein wall; kynurenine and tricarboxylic acid pathway dysfunction were reported. Future research should focus on targeted studies with internal and external validation