Management of patients with protein s deficiency: focus on clinical course and direct oral anticoagulants.

Abstract

BACKGROUND: 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.