Reduced-dose direct oral anticoagulants in protein S deficient patients yielded a higher rate of venous thromboembolic events than full-dose therapy (8.1 vs 0 per 100 patient-years, P=0.033).
Cohort (n=33)
No
Is reduced dose DOAC effective in secondary prevention of VTE in patients with Protein S deficiency compared to full dose DOAC?
A reduced dose of DOACs is only partially effective in secondary prevention of VTE in patients with Protein S deficiency, with recurrences occurring exclusively during the reduced-dose phase.
Absolute Event Rate: 8.1% vs 0%
p-value: p=0.033
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. 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). 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). 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.
Nicola et al. (Fri,) conducted a cohort in Protein S deficiency (n=33). Reduced-dose direct oral anticoagulants (apixaban or rivaroxaban) vs. Full-dose direct oral anticoagulants (apixaban 5 mg BID or rivaroxaban 20 mg once a day) was evaluated on Venous thromboembolic events (VTE) incidence rate per 100 patient-years (95% CI 4-15, p=0.033). Reduced-dose direct oral anticoagulants in protein S deficient patients yielded a higher rate of venous thromboembolic events than full-dose therapy (8.1 vs 0 per 100 patient-years, P=0.033).