¹Tariq Abdullah Said Al-Araimi, ¹Shaikha Said Saleh Al-Saadi

¹Royal Hospital

Purpose Statement: Introduction

Thrombotic Thrombocytopenic Purpura (TTP) is an immune Thrombotic Microangiopathy (TMA) classified as primary or secondary to autoimmune diseases like Systemic Lupus Erythematosus (SLE). This type of TMA results from reduced activity of the von Willebrand factor-cleaving protease due to antibodies against ADAMTS131. Despite treatment, SLE-related TTP mortality ranges from 34% to 62.5%, higher than the 20% in idiopathic TTP2,3. We present a case where TTP, as an initial SLE manifestation, had a challenging course after failing conventional treatments.

Method(s): A 27-year-old female patient presented with alopecia, headache, blurred vision due to retinal vasculitis, and ischemic stroke. Investigations revealed anemia, thrombocytopenia, hypocomplementemia, acute kidney injury, and retinal vasculitis. Peripheral blood smear showed schistocytes, suggesting TTP. Treatment began with plasma exchange (PEX) and high-dose corticosteroids. Further labs showed a reactive ANA titre of 1:640 and anti-Ds DNA. SLE diagnosis was confirmed, and initial treatment included cyclophosphamide, which was switched to rituximab due to intolerance, alongside PEX, steroids, Mycophenolate, and Hydroxychloroquine. Bortezomib was added for refractory disease due to the unavailability of caplacizumab.

Result(s): Low ADAMTS13 activity and a positive inhibitory ADAMTS13 antibody were observed. Despite the use of multiple immunosuppressants and plasma exchange (PEX), the disease remained refractory. After conducting a lymphocyte subset analysis to confirm B cell depletion due to Rituximab, Bortezomib was introduced, leading to normalization of platelet counts within 3 days and normalization of ADAMTS13 activity 10 days later, while maintaining an excellent response at the 12-month follow-up on Mycophenolate Mofetil and Hydroxychloroquine.

Conclusion(s): Plasma exchange and immunosuppressive medications are standard for acquired autoimmune TTP, with case reports suggesting benefits from additional agents like bortezomib for eliminating auto-reactive plasma cells4,5. This case uniquely contributes to the limited literature on Bortezomib in refractory lupus TTP6,7. Early diagnosis of SLE  is crucial for patient care, maintenance therapy, and monitoring for complications. Further studies are needed to confirm Bortezomib’s efficacy and long-term outcomes in SLE-associated TTP.