LAUSR

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy (TMA) syndrome (Kremer et al. 2017). TTP typically includes severe thrombocytopenia, microangiopathic hemolytic anemia (MAHA) with schistocytes and organ manifestations secondary to microvascular thrombosis (neurological symptoms, acute kidney injury (AKI), myocardial infarction), associated with severe functional deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) (Joly et al, 2019). The majority of acquired TTP in adults are related to an auto-immune disorder where antiADAMTS13 antibodies cause that deficiency and subsequent platelet adhesion and aggregation.Bacterial infections, autoimmune diseases, pregnancy, drugs, HIV infection, cancers, organ or HSC transplantation are the most frequent clinical conditions associated with TTP (Joly et al, 2019).Lenalidomide, an immunomodulatory drug, is a treatment of multiple myeloma (MM), myelodysplastic syndromes. Most frequent adverse effects are cytopenias, infections and thrombosis. We report 3 new cases of acquired autoimmune TTP in patients treated with Lenalidomide. A 69-year-old female, with a 10-year history of MM (multiple myeloma) IgG kappa, received lenalidomide (10 mg daily) plus dexamethasone (20 mg weekly) for a second relapse. In April 2017, while in partial response after five months of treatment, she developed dizziness, ataxia, visual field abnormalities and left upper limb dyskinesia. She presented with haemoglobin 80 g/l, platelets 4 9 10/l, high reticulocyte count 180 9 10/l, elevated LDH 1200 UI/l, decreased haptoglobin, no schistocytes on blood smears and a creatinine level of 11 mg/l. A direct antiglobulin test was negative and complement (C3, C4 and CH50) levels were normal. A brain MRI showed several cortical and non-cortical cerebrovascular infarctions. ADAMTS13 activity was undetectable at <5%, with presence of anti-ADAMTS13 IgG (>100 U/ml). Lenalidomide was stopped and the patient benefited from 16 therapeutic plasma exchanges (TPE), with methylprednisolone 1 mg/kg daily, tapered over a month, resulting in a rise of the platelet count till 70 9 10/l, and a normalisation of LDH levels – neurological symptoms progressively disappeared. Ten months later, the platelet count remained stable at 67 9 10/l with a normal ADAMTS13 activity (88%). She is currently treated with bortezomib, cyclophosphamide and dexamethasone in a partial haematological response. A 70-year-old woman was treated with lenalidomide (10 mg daily) from June 2014 for refractory anaemia, 5q-syndrome. After three months of treatment, she presented with fever, abdominal pain and right upper limb paresis, haemoglobin 40 g/l, platelets 2 9 10/l, high LDH levels (1560 U/l), low haptoglobin, the presence of schistocytes on blood smear, oliguric AKI (17 mg/l), and a high level of troponin. ADAMTS13 activity was undetectable at <5%, associated with anti-ADAMTS13 IgG (190 U/ml). CT scans revealed multiple ischemic events: infarctions of cerebrum,