Background: Literature has paid little attention in describing the specific contribution of each modifiable and nonmodifiable characteristics on health-related quality of life (HRQoL) in physician-managed anticoagulated patients using vitamin K antagonists (VKAs). To describe how patients' treatment-specific knowledge, health literacy, treatment beliefs, clinical, and socio-demographic characteristics influence HRQoL in Italian physician-managed anticoagulated patients using VKAs. Methods: Cross-sectional multicentre study with a consecutive sampling strategy, enrolling 164 long-term anticoagulated patients. Clinical and socio-demographic characteristics were collected from electronic medical records. Valid and reliable questionnaires were used to collect patients' treatment-specific knowledge, health literacy, beliefs about VKAs, physical and health perceptions. Results: Obtaining and understanding health information (i.e., communicative health literacy) positively predicts both adequate mental (OR adjusted = 10.9; 95%CI = 1.99-19.10) and physical (OR adjusted = 11.54; 95%CI = 1.99-34.45) health perceptions. Conversely, the ability to perform proper health decision making (i.e., critical health literacy) was associated with lower rates of adequate mental health perception (OR adjusted = 0.13; 95%CI = 0.03-0.63). Further, age negatively predicted physical health perception (OR adjusted = 0.87; 95%CI = 0.81-0.93). Conclusions: Health literacy plays an interesting role in predicting HRQoL. The relationship between critical health literacy and mental health perception could be influenced by some psychological variables, such as distress and frustration, which could be present in patients with higher levels of critical health literacy, as they could be more inclined for self-monitoring. For this reason, future research are needed to identify the most suitable patients' profile for each OAC-management model, by longitudinally describing the predictive performance of each modifiable and non-modifiable determinant of HRQoL.
