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Haematologic involvement in patients with systemic lupus erythematosus (SLE) is very common. The principal cytopenias in lupus result in anaemia, white cell deficits and thrombocytopenia.Anaemia may be microcytic (due e.g. due to blood loss); normocytic (e.g. due to immunosuppression); macrocytic (e.g. due to concomitant hypothyroidism or pernicious anaemia) or haemolytic, characterized by an increased reticulocyte count and a positive Coombs test.Abnormal white blood cell counts in patients with SLE often present as leukopenia, a condition found in up to two-thirds of patients at diagnosis. It is crucial to distinguish this from medication side effects. Other abnormalities include neutropenia (a low neutrophil count), which may be caused by immunosuppression or, in rare cases, macrophage activation syndrome, and lymphopenia (a low lymphocyte count), which is observed in up to 80% of patients and may or may not be associated with disease activity.Thrombocytopenia may occur in the ‘pre-lupus stage’ when platelet counts can be very low (i.e. <25 x 109/L), ‘chronic persistent’ (platelet counts 50–125 are often associated with antiphospholipid antibodies (aPL) or ‘acute dramatic’ when platelet count may again be very low and require urgent treatment.Symptoms of these various conditions are highly variable and depend on the severity of the problem. Similarly, treatment approaches vary. In some cases, simply reducing or stopping immunosuppression may correct anaemia and neutropenia. However, for severe thrombocytopenia (low platelet count), especially when the count drops below 20, more aggressive treatment may be necessary. This can include intravenous steroids, immunoglobulin, or rituximab.Case 1: Haematological manifestations of SLE and B-cell depletion In 2001 one of the very first patients I treated with rituximab had presented with joint pains and skin rashes with a strongly positive antinuclear antibody and anti-DNA antibody, but did not have aPL antibodies. However, both her haemoglobin and platelet counts were persistently low and showed only transient responses to a variety of treatments including steroids, conventional immunosuppression and platelet transfusions. However, both her low haemoglobin and low platelet counts were corrected dramatically with B-cell depletion using rituximab and cyclophosphamide. The normalisation of both the haemoglobin and platelet count lasted several years. Prior to the introduction of B-cell splenectomy had been offered to these patients with somewhat variable results.Case 2: A 42-year-old female with SLE and refractory haemolytic anaemia This patient had a 10-year history of systemic lupus erythematosus (SLE), initially presenting with fatigue, polyarthritis, malar rash, hair loss, leukopenia, Coombs-positive autoimmune haemolytic anaemia (AIHA), and positive ANA and anti-dsDNA antibodies. At diagnosis, she already exhibited splenomegaly (14 cm), attributed to red blood cell destruction and underlying autoimmunity. While on hydroxychloroquine, she required chronic glucocorticoid therapy (7.5–15 mg/day) to maintain haemoglobin levels in the range of 9–9.5 g/dL. She failed multiple conventional immunosuppressants, including ciclosporin, azathioprine, and mycophenolate, with worsening leukopenia (2,200–3,000/mm³) and autoimmune haemolytic anemia (drop in haemoglobin and haptoglobin, rise in lactate dehydrogenase). Imaging revealed further increased spleen size without other organomegaly or lymphadenopathy. Rituximab (anti-CD20 mAb) was administered, but elicited no response, and she continued to require >10–20 mg/day of prednisone equivalent. Given this refractory disease course, we discuss the need for additional diagnostic work-up and as well as the pros and cons of different management options, including cyclophosphamide, off-label therapies and splenectomy.Case 3: A 60-year-old male with haemolytic anaemia and triple-positivity for antiphospholipid antibodies This man had no significant medical history and presented acutely with severe thrombocytopenia (<20,000/μL), acute kidney injury, and peripheral smear evidence of microangiopathic haemolytic anaemia. Chest CT revealed a pulmonary embolism. Initial management included anticoagulation, plasma exchange, rituximab, and high-dose glucocorticoids. Work-up revealed triple positivity for antiphospholipid antibodies, with normal ADAMTS13 activity. The patient experienced multiple relapses with recurrent thrombocytopenia, raising suspicion for APS-related or complement-mediated thrombotic microangiopathy (TMA). In response, immunosuppressive therapy was intensified and complement inhibition initiated, resulting in rapid clinical improvement.Learning Objectives At the end of this workshop participants will be able to:Describe the recommended treatment of SLE-related autoimmune haemolytic anaemiaDiscuss the role for splenectomy in the setting of refractory autoimmune haemolytic anaemiaExplain the differential diagnosis of microangiopathic haemolytic anaemia focusing on exploring TMADiscuss the emerging role of complement inhibitors for TMA-associated pathologies