A relapse of these patients often happens with conditions associated with an increased release of large von Willebrand multimers such as stress, infection, autoimmune diseases or pregnancy

A relapse of these patients often happens with conditions associated with an increased release of large von Willebrand multimers such as stress, infection, autoimmune diseases or pregnancy. both persistently low ADAMTS13 activity and a detectable inhibitor activity due to reducing the release of von Willebrand factor large multimers from the endothelial cells. We found that ADAMTS13 activity normalized and the inhibitor activity became undetectable when cyclophosphamide was added to rituximab. We suggest adding cyclophosphamide to rituximab for the treatment of patients with persistent ADAMTS13 inhibitors in order to prolong the remission period and lower the rate of relapse. strong class=”kwd-title” Key Words: ADAMTS13, Idiopathic relapsing thrombotic thrombocytopenic purpura, Plasmapheresis, Rituximab Introduction Thrombotic thrombocytopenic purpura (TTP) is usually associated with a decrease in the activity of the Rabbit Polyclonal to MNT von Willebrand factor-cleaving protease ADAMTS13. This decrease can be due to a congenital deficiency or the presence of an inhibitor. The treatment of TTP in the presence of an inhibitor is usually plasmapheresis to remove the inhibitor and to replenish ADAMTS13. We here describe a patient with an idiopathic TTP secondary to ADAMTS13 inhibitor that continued to be dependent on plasmapheresis until she was treated with rituximab. TTP manifestations subsided with rituximab treatment in spite of a persistently low ADAMTS13 activity and continued detectable inhibitor activity until the patient developed an intolerance to rituximab due to an allergic reaction when cyclophosphamide was added; this resulted in a normalization of her ADAMTS13 activity and the disappearance of the inhibitor. Case Presentation A 53-year-old African American woman with a past medical history of hypertension presented with abdominal pain, dizziness and confusion. At K-Ras G12C-IN-3 presentation, her platelet count was 14,000/mm3, lactate dehydrogenase 896 IU/l (normal value 98C192) and a peripheral smear showed increased schistocytes. She was diagnosed with TTP. Her ADAMTS13 activity was 5% (normal value 67%) and her inhibitor level was 0.5 inhibitor units (normal value 0.4 inhibitor units). She was treated with plasmapheresis and prednisone with an improvement in the platelet count, but she required ongoing plasmapheresis for several months with a failure to wean off her plasmapheresis. Her evaluation included a bone marrow biopsy, CT scans to rule out malignancy, an autoimmune and infectious workup C all were negative. She was later treated with rituximab 375 mg/m2 weekly 4 doses, and she was weaned off plasmapheresis. Rituximab was continued as a maintenance therapy initially every 3 months, and then every 6 months with a normal platelet count; however, ADAMTS13 activity remained 5%, accompanied with a high inhibitor level of up to 2 inhibitor models. Rituximab was stopped after 4 years of treatment. Seven months after rituximab stoppage, she presented with a TTP recurrence and a platelet count of 17,000/mm3. Rituximab was reintroduced; however, she started having allergic reactions even at a very low infusion rate and despite antihistamine and corticosteroid K-Ras G12C-IN-3 treatment. Cyclophosphamide as an immunosuppressant was added to rituximab at 1 K-Ras G12C-IN-3 g/m2 every 3 months in a trial to lower the ADAMTS13 inhibitor titer. TTP went into remission once rituximab and cyclophosphamide were restarted, with a normalization of her platelet count. After 2 cycles of cyclophosphamide, the inhibitor and ADAMTS13 activity started to K-Ras G12C-IN-3 decrease, and by the fourth cyclophosphamide treatment, ADAMTS13 activity became normal at 67% with an undetected inhibitor level. K-Ras G12C-IN-3 Later, the patient developed an intolerance to rituximab due to a severe allergic reaction even at a very low infusion rate. Soon after stopping rituximab, ADAMTS13 activity levels decreased below 5% in addition to an appearance of ADAMTS13 inhibitors. The patient had a splenectomy after rituximab and cyclophosphamide treatment based on several case reports of a complete remission of TTP after splenectomy. Discussion TTP is usually a life-threatening disease with a mortality rate of almost 90% if left untreated. It manifests as disseminated thrombotic microangiopathy, thrombocytopenia, hemolytic anemia, neurologic and renal dysfunction as well as fever [1, 2, 3]. TTP can be congenital or idiopathic, associated with anti-ADAMTS13 antibodies (autoimmune TTP), or secondary TTP associated with contamination, pregnancy, and medications such as tacrolimus, mitomycin and cyclosporine A [4, 5, 6, 7, 8]. Congenital TTP is frequently associated with a severe ADAMTS13 deficiency. TTP patients with ADAMTS13 inhibitors respond to plasma exchange.