Management of patients with protein s deficiencyAltamura, Nicola (Avtor) Di Girolamo, Filippo Giorgio (Avtor) Pradella, Paola (Avtor) Cavalet, Martina (Avtor) Pellicori, Federica (Avtor) Vinci, Pierandrea (Avtor) Panizon, Emiliano (Avtor) Cominotto, Giovanni (Avtor) Teraž, Kaja (Avtor) Biolo, Gianni (Avtor) thrombophiliareduced-dose DOACbleedingthromboembolic eventsBackground Protein S (PS) is a cofactor of protein C (PC) which, when activated to activated PC (APC), mainly acts to degrade coagulation factor Va and VIIIa, and its deficiency may trigger an array of venous thromboembolic events (VTE); when unprovoked and life-threatening, these need indefinite anticoagulation. Direct oral anti coagulants (doac) are efficient drugs in therapy and prevention of VTE, although the optimal prophylactic doses in different conditions are not identified. Methods General characteristics and clinical events of 33 PS deficient patients (7 uneventful, 10 carrying also other thrombophilic conditions) were recorded from their medical records. Patients suffering from VTE underwent LMWH/Fondaparinux therapy followed by a full dose of doac (apixaban or rivaroxaban) and then a reduced dose doac (apixaban and rivaroxaban). Results Average, lowest and highest PS levels measured during follow-up were higher in male patients (p = 0.001). The cumulative prevalence of patients taking drugs acting on central nervous system (opioids, antidepressants, antiepileptic, antimigraine, antipsychotic) was 33%. Three minor hemorrhages were observed during the full-dose and one during the reduced doac therapy, while 3 VTE (1 pulmonary embolism and 2 deep venous thrombosis) occurred exclusively during the reduced-dose doac therapy (p = 0.033 Vs Full dose, 8.1 100patient/yr 95% CI 4–15). Compliance during the reduced-dose therapy was good according to the circulating levels of doac. In survival analysis, the only variable associated with VTE recurrence was PS deficiency combined with thrombophilic defects (p = 0.049). Conclusions Free PS deficiency affects the quality of life in many ways and a low dose doac in PS deficient patients is only partially effective in secondary prevention of VTE.20262026-04-16 11:18:39Neznano29003sl© The Author(s) 2026.