The Platelet Activating Factor–Platelet Activating Factor Acetylhydrolase Enzyme Axis in Anaphylaxis: Current Evidence and Future Perspectives

Anaphylaxis is a severe systemic hypersensitivity reaction characterized by rapid onset, unpredictable clinical course, and potentially fatal outcomes. Although its diagnosis remains primarily clinical, the identification of biomarkers capable of improving risk stratification and understanding disease mechanisms remains an important unmet need. Among the mediators implicated in anaphylaxis, platelet-activating factor (PAF) has emerged as a key effector molecule involved in vascular permeability, bronchoconstriction, platelet activation, and cardiovascular dysfunction. The biological activity of PAF is tightly regulated by platelet-activating factor acetylhydrolase (PAF-AH), the enzyme responsible for its degradation, making the PAF–PAF-AH axis a potentially important determinant of reaction severity. OBJECTIVES: The present review summarizes current knowledge regarding the biology of PAF and PAF-AH and examines their role in the pathophysiology of anaphylaxis, with particular emphasis on Hymenoptera venom allergy (HVA). The therapeutic potential of targeting the PAF pathway is also discussed. Experimental and clinical evidence consistently suggests an association between increased PAF activity, reduced PAF-AH activity, and more severe anaphylactic reactions. However, methodological limitations, biological variability, and conflicting findings across studies currently limit the clinical applicability of these molecules as standalone biomarkers. Overall, the PAF–PAF-AH axis represents a biologically plausible link between molecular mechanisms and clinical severity in anaphylaxis. Further studies are required to standardize measurements, validate clinical utility, and define the role of this pathway as both a biomarker and therapeutic target; hence gaining insight into PAF’s role in various biological processes is critical.