Atypical presentations of thrombotic thrombocytopenic purpura in middle-aged women with recurrent cerebral macrovascular thrombosis: a case report

Abstract

Dear Editor, In the current clinical practice, minimal criteria to define thrombotic thrombocytopenic purpura (TTP) are the presence of signs of microangiopathic haemolytic anaemia and low platelet (PLT) count [1]. TTP relapses (20–50 % of cases) are defined as the recurrence of acute TTP symptoms 30 days after the first episode, while exacerbations occur within 30 days [2]. We here report on an atypical case of acquired TTP where minimal criteria were met only after many recurrent macrovascular ischemic events. A 42-year old Caucasian woman with a history of coronary and cerebral ischemic events was admitted on June 2013, following a recurrent transient ischemic attack (TIA). She had severe anaemia and thrombocytopenia with laboratory signs of intravascular haemolysis and mild renal impairment. In her past medical history, recurrent ischemic events occurred from 2008 to 2012, without known risk factors and regardless of treatment. The patient was treated with acetyl salicylic acid (100 mg daily) after the first ischemic event (stroke, in 2008) plus anticoagulation with warfarin after the third stroke (in 2010), with a good compliance . Screening for autoimmune disease, Factor V Leiden and Factor II (G20210A) gene mutations and circulating anticoagulants were normal. Blood cell count and peripheral blood smear did not show any significant abnormalities in the past, without evidence of schistocytes; a slight decrease in PLT count (92×109/L) was observed only once (in 2012), at that time, ADAMTS13 activity (ADAMTS-13: AC) was 65 %. At the current admission, ADAMTS-13: AC was 6 %, inhibitors were at high titer (2 Bethesda Units, BU). A genetic test for Upshaw-Schulman syndrome was normal. Therapeutic plasma exchange (TPE) and prednisone (1 mg/kg body weight) treatment was started and maintained until clinical and haematological remission [3]. TPE (Gambro®, Italy) was performed daily for 3 weeks with an increase of ADAMTS13: AC to 50 %. TTP exacerbated after 10 days, it was well controlled with weekly rituximab (375 mg/m body surface), for 4 weeks. A relapse occurred after 37 days with the patient presenting seizures: ADAMTS-13: AC, which was 54 % after the last treatment, had decreased to 6 %. A second course of weekly rituximab, followed by maintenance with azathioprine (50 mg twice daily for 10 days, then 50 mg, daily) was followed by clinical and haematological remission. Rituximab was re-administered for its previous rapid efficacy and to prevent further complications [4]. The patient is alive and free from recurrences for 18 months; azathioprine maintenance is still on course. ADAMTS13: AC is monitored every 4 months, and it ranges from 45 to 51 %; inhibitors are no longer detectable. * Alessandro Lucchesi alessandro.lucchesi@irst.emr.it