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Rituximab-Cyclophosphamide-Dexamethasone (RCD) Combination In the Management of Autoimmune Cytopenias Associated with Chronic Lymphocytic Leukaemia

Severe autoimmune intravascular hemolytic anemia in patients receiving alemtuzumab for multiple sclerosis

Clinical characteristics, treatment strategies, and response patterns in evans syndrome: Initial analysis from the spanish resti cohort

Clinical Spectrum, Evolution and Management of Autoimmune Cytopenia Associated with Angioimmunoblastic T-Cell Lymphoma: A Retrospective, Multicenter Study

Effect of Treatment with Rituximab in Patients with Refractory Autoimmune Cytopenias.

Critical role of Th17 cells in development of autoimmune hemolytic anemia

Simultaneous onset of autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) is rare and any possible association between these two disorders remains obscure. A 46-year-old previously healthy woman was diagnosed as having AIHA based on severe anemia, positive direct and indirect Coomb's tests, decreased serum haptoglobin, elevated serum LDH, and indirect bilirubin-dominant hyperbilirubinemia. Oral steroid administration (1 mg/kg) and subsequent half-pulse steroid therapy ameliorated the AIHA, but the anemia was unexpectedly prolonged with the low peripheral blood reticulocyte count further decreasing to 0.11%. Bone marrow aspiration revealed a marked decrease in erythroblasts with an M/E ratio of 69.5. Anti-parvovirus B19 IgM antibody and serum B19 viral DNA (109 copy/ml) were detected but no other distinct abnormalities which might have caused acquired PRCA were detected. Therefore, she was considered likely to have idiopathic AIHA and acquired PRCA simultaneously. AIHA-mediated erythroblastosis probably raised the parvovirus B19 DNA level to an extraordinary degree and thereby led to severe aplastic crisis, subsequently causing prolonged anemia. Parvovirus B19 infection should be considered in AIHA patients showing unexpectedly low reticulocyte counts.

Chronic Lymphocytic Leukaemia (CLL) is commonly associated with autoimmune cytopenias but CLL presenting with pancytopenia is a rare occurrence. Here, we present a case of 56-year-old male patient, who presented with pallor, mild hepatosplenomegaly, right-sided pleural effusion in chest x-ray, pancytopenia and his bone marrow showed infiltration by mature appearing lymphoid cells making a diagnosis of CLL. Despite the frequency of these immune mediated cytopenia, only few cases of pancytopenia have been described so far to the best of our knowledge. Hence, to emphasise the rarity of such haematological coincidence we are presenting this case report. CLL generally presents with persistent absolute lymphocytosis on peripheral smear with an absolute monoclonal lymphocyte count of more than 5000/cumm. There is a common association with Autoimmune Haemolytic Anaemia (AIHA) and Immune Thrombocytopenia (ITP) and the association is called as Evan’s syndrome. Its pathogenesis is associated with autoimmune process. AIHA, ITP, and Pure Red Cell Aplasia (PRCA) are commonly associated complications seen in CLL. The pathogenesis of AIHA and ITP are antibody this inplace of the reactions and abnormal T cell activity is noted in the pathogenesis of PRCA. Despite of the frequency of these immune mediated cytopenias noted in CLL, bone marrow was seen to be hypercellular in most of the cases and marrow hypoplasia have been reported in only 2 cases reported in literature so far. In the present case, although pancytopenia was present on peripheral blood smear examination but bone marrow was hypercellular for age with diffuse infiltration by monoclonal mature appearing lymphoid cells which makes this case all the more interesting. Despite repeated blood transfusions,antiviral drug Tenofovir and aggressive supportive measures for 6 months, he developed right-sided pleural effusion and succumbed to his illness.

Exploration of B and T Cell Receptor Repertoires Reveals Distinct Mechanisms in Pure Red Cell Aplasia, Autoimmune Hemolytic Anemia, and Aplastic Anemia

Evans syndrome is an autoimmune disorder described by Robert Evans in 1951 specifying that a link exists between primary thrombocytopenic purpura and acquired haemolytic anaemia. It is a rare autoimmune disorder characterised by the simultaneous or sequential development of autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) with or without immune neutropenia. Approximately, Evans syndrome represent 5-10% of warm autoimmune haemolytic anaemia cases and 2-5% of ITP cases. It is basically a diagnosis of exclusion. We present a 50-year-old female presented with anaemia, jaundice and petechia. Patient indirect bilirubin was raised, Coombs test was positive, lactate dehydrogenase and reticulocyte count were raised. Based on the Coombs positive haemolytic anaemia and thrombocytopenia patient was diagnosed with Evans syndrome. ANA profile was positive for SS-A suggestive of underlying autoimmune disorder. Evans syndrome is difficult to diagnose and treat. Typically, corticosteroids and other immunosuppressive medications are used to manage the syndrome.

Immune-Related Hematologic Adverse Events in the Context of Checkpoint Inhibitors

A 53-year old man with systemic lymphadenopathy and hepatosplenomegaly was diagnosed with diffuse large B cell-lymphoma after inguinal lymph node biopsy. Anemia was noted, direct and indirect Coombs tests were positive, and the haptoglobin level was low. However, the bone marrow aspirate revealed erythroid aplasia. Co-existing autoimmune haemolytic anemia (AIHA) and pure red cell aplasia (PRCA) were diagnosed. In situ hybridization with Epstein-Barr virus (EBV) encoded small RNA (EBER) showed positive findings in lymphoma cells. Southern blot hybridization revealed immunoglobulin heavy chain gene rearrangement and a clonal EBV terminal repeat, indicating monoclonal proliferation of EBV in infected B cells. The patient was treated with CHOP, resulting in a complete remission (CR). AIHA and PRCA subsided after 3 courses of chemotherapy. In conclusion, this case demonstrates not only the association of B-cell lymphoma with autoimmune disorders but also the involvement of EBV in these conditions.

Background: Autoimmune haemolytic anaemia (AIHA) during pregnancy is a rare finding, and few is known about maternal and foetal outcomes. AIHA may either develop or relapse during gestation and postpartum or be an issue in a patient on active therapy who becomes pregnant. AIHA management during pregnancy and lactation is not standardized and drug use is often limited by safety concerns. Aims: We studied AIHA impact on pregnancy focusing on disease severity, treatment need and maternal/foetal outcome. Methods: Through a multicentric retrospective cohort study, we identified 38 pregnancies occurred in 28 women from 1997 to 2021 in 10 European centres in Italy, Denmark, France, the Netherlands, USA, and Spain. All included patients had a previous AIHA history or developed/exacerbated AIHA during gestation or postpartum. AIHA was classified according to the direct antiglobulin test. Results: We registered 18 warm AIHA (10 IgG; 8 IgG+C3d), 2 cold agglutinin disease, 3 mixed and 5 atypical forms (Table 1). Evans syndrome (i.e., association of AIHA and immune thrombocytopenia or neutropenia) was present in 4. Mean age at AIHA diagnosis was 27 (3-39) and at pregnancy 32 (21-41) years. AIHA diagnosis predated pregnancy in 15 women and had required at least 1 therapy line in all of them, and ≥2 lines in 12 (rituximab, N=7; cytotoxic immunosuppressants, N=6; splenectomy, N=5). Among these 15 patients, 6 had a relapse during pregnancy, 3 during postpartum and 9 were on active treatment at the time of pregnancy (steroids, N=8; cyclosporine, N=1; azathioprine, N=1; the latter stopped after positive pregnancy test). A patient with a previous AIHA, relapsed as immune thrombocytopenic purpura during pregnancy. Further 8 patients had an AIHA onset during gestation and 2 postpartum. A patient had AIHA onset during the postpartum of the 1st pregnancy and relapsed during the 2nd one. In the 20 women experiencing AIHA during pregnancy/postpartum, median Hb and LDH levels were 6,4 g/dL (3,1 – 8,7) and 588 UI/L (269-1631), respectively. Management consisted in blood transfusions (N=10) and prompt establishment of steroid therapy+/-IVIG (N=20), all with response (complete N=13, partial N=7). After delivery, rituximab was necessary in 4 patients and cyclosporine was added in one. Anti-thrombotic prophylaxis was given in 7 patients. Overall, we registered 10 obstetric complications (10/38, 26%), including 4 early miscarriages, a premature rupture of membranes, a placental detachment, 2 preeclampsia, a postpartum infection and a biliary colic. Apart from the case of biliary colic and one of the two cases of preeclampsia, 8/10 complications occurred during active haemolysis and treatment for AIHA. Nine foetal adverse events (9/38, 24%) were reported: a transitory respiratory distress of the new-born in a mother with active AIHA, 3 cases of foetal growth restriction, a preterm birth, an infant reporting neurologic sequelae, a case of AIHA of the new-born requiring intravenous immunoglobulins, blood transfusions and plasma exchange, and 2 perinatal deaths. The latter both occurred in women on active AIHA therapy and were secondary to a massive placental detachment and a symptomatic SARS-CoV-2 infection. Image:Summary/Conclusion: AIHA developing/reactivating during pregnancy or postpartum is rare (about 5%) but mainly severe requiring steroid therapy and transfusions. Importantly, severe maternal and foetal complications may occur in up to 26% of cases mostly associated with active disease, pinpointing the importance of maintaining a high level of awareness. Passive maternal autoantibodies transfer to the foetus seems a rare event.

Incidence of False-Positive Direct Anti Globulin Tests (DAT): A Single-Center Retrospective Analysis.

Autoimmune Hemolytic Anemia In Cancer Patients At a Tertiary Center In Southern Nigeria