Rituximab in Warfarin Resistance Treatment in Patients with Thrombophilia Due to Primary Antiphospholipid Syndrome: A Pilot Study.

Introduction: The inability to obtain a therapeutic value of the INR regardless of the warfarin high doses administration represents a significant problem to resolve in the oral anticoagulation therapy, this phenomena is called “Warfarin Resistance”. Based on the experience and success of Rituximab in the treatment of autoimmune diseases like Immune Thrombocytopenic Purpura, we treated 7 patients with Primary Antiphospholipid Syndrome (PAS) and Warfarin Resistance.

Objective: To assess if Rituximab can revert the warfarin resistance in patients with thrombophilia associated to PAS

Material and Methods: We evaluated 7 patients with PAS who were receiving 15 mg of warfarin and had persistent low INR values. Rituximab was given weekly at dose of 375 mg/m2 for 4 doses. Effectiveness and safety were registered weekly during 2 months since the start of treatment with clinical evaluation and INR, aPTT, warfarin serum levels and CD20 blood lymphocytes count determinations.

Results: All patients were women with a mean of 35 years old (37– 48) and INR of 1.11 (0.79–1.50). All the patients (100%) reached the therapeutic level of INR between days 8 to 15, but the response lasted only a mean of 24 days (8 – 40). The maximum INR values were observed through the 2nd to the 3rd doses of Rituximab. The warfarin serum levels did not change during the assessment period.

Conclusion: Rituximab was effective in reverting resistance to Warfarin therapy in patients with thrombosis for primary Antiphospholipid Syndrome, however it lasted a very short time and eventually all patients relapsed.