Autoimmune hemolytic anemia during pregnancy and puerperium: an international multicenter experience.

Relapsing or occurring de novo autoimmune hemolytic anemia (AIHA) during pregnancy or puerperium is a poorly described condition. Here, we report 45 pregnancies in 33 women evaluated at 12 centers from 1997 to 2022. Among the 20 women diagnosed with AIHA before pregnancy, 10 had a relapse. An additional 13 patients developed de novo AIHA during gestation/puerperium (2 patients had AIHA relapse during a second pregnancy). Among 24 hemolytic events, anemia was uniformly severe (median Hb, 6.4 g/dL; range, 3.1-8.7) and required treatment in all cases (96% steroids ± intravenous immunoglobulin, IVIG, 58% transfusions). Response was achieved in all patients and was complete in 65% of the cases. Antithrombotic prophylaxis was administered to 8 patients (33%). After delivery, rituximab was administered to 4 patients, and cyclosporine was added to 1 patient. The rate of maternal complications, including premature rupture of membranes, placental detachment, and preeclampsia, was 15%. Early miscarriages occurred in 13% of the pregnancies. Fetal adverse events (22% of cases) included respiratory distress, fetal growth restriction, preterm birth, AIHA of the newborn, and 2 perinatal deaths. In conclusion, the occurrence of AIHA does not preclude the ability to carry out a healthy pregnancy, provided close monitoring, prompt therapy, and awareness of potential maternal and fetal complications.

Evaluating patients with autoimmune hemolytic anemia in the transfusion service and immunohematology reference laboratory: pretransfusion testing challenges and best transfusion-management strategies.

The serologic evaluation of autoimmune hemolytic anemia (AIHA) confirms the clinical diagnosis, helps distinguish the type of AIHA, and identifies whether any underlying alloantibodies are present that might complicate the selection of the safest blood for any needed transfusion. The spectrum of testing is generally dependent on the amount and class (immunoglobulin G or M) of autoantibody as well as the resources and methodologies where testing is performed. The approach may range from routine pretransfusion testing, including the direct antiglobulin test, to advanced techniques such as adsorptions, elution, and red cell genotyping. When transfusion is needed, the selection of the optimal unit of red blood cells is based on urgency and whether time allows for the completion of sophisticated serologic and molecular testing methods. From the start of when AIHA is suspected until the completion of testing, communication among the clinical team and medical laboratory scientists in the transfusion service and immunohematology reference laboratory is critical as testing can take several hours and the need for transfusion may be urgent. The frequent exchange of information including the patient's transfusion history and clinical status, the progress of testing, and any available results is invaluable for timely diagnosis, ongoing management of the patient, and the safety of transfusion if required before testing is complete.

Updates in the Management of Warm Autoimmune Hemolytic Anemia.

Warm autoimmune hemolytic anemia (wAIHA) is an uncommon and heterogeneous disorder caused by autoantibodies to RBC antigens. Initial evaluation should involve the DAT, with wAIHA typically IgG positive with or without C3 positivity, and a search for underlying conditions associated with secondary wAIHA, which comprise 50% of cases. First-line therapy involves glucocorticoids, increasingly with rituximab, though a chronic relapsing course is typical. While splenectomy and a number of immunosuppressive therapies have been used in the setting of relapsed and refractory disease, the optimal choice and sequence of therapies is unknown, and clinical trials should be offered when available. Newer investigational targets include spleen tyrosine kinase inhibitors, monoclonal antibodies targeting CD38, Bruton's tyrosine kinase inhibitors, complement inhibitors, and antibodies against neonatal Fc receptors.

Autoimmune hemolytic anemia: causes and consequences.

INTRODUCTION: Autoimmune hemolytic anemia (AIHA) is classified according to the direct antiglobulin test (DAT) and thermal characteristics of the autoantibody into warm and cold forms, and in primary versus secondary depending on the presence of associated conditions. AREAS COVERED: AIHA displays a multifactorial pathogenesis, including genetic (association with congenital conditions and certain mutations), environmental (drugs, infections, including SARS-CoV-2, pollution, etc.), and miscellaneous factors (solid/hematologic neoplasms, systemic autoimmune diseases, etc.) contributing to tolerance breakdown. Several mechanisms, such as autoantibody production, complement activation, monocyte/macrophage phagocytosis, and bone marrow compensation are implicated in extra-/intravascular hemolysis. Treatment should be differentiated and sequenced according to AIHA type (i.e. steroids followed by rituximab for warm, rituximab alone or in association with bendamustine or fludarabine for cold forms). Several new drugs targeting B-cells/plasma cells, complement, and phagocytosis are in clinical trials. Finally, thrombosis and infections may complicate disease course burdening quality of life and increasing mortality. EXPERT OPINION: Beyond warm and cold AIHA, a gray-zone still exists including mixed and DAT negative forms representing an unmet need. AIHA management is rapidly changing through an increasing knowledge of the pathogenic mechanisms, the refinement of diagnostic tools, and the development of novel targeted and combination therapies.

Complications of Autoimmune Hemolytic Anemia.

Autoimmune hemolytic anemia (AHIA) is the group of acquired autoimmune conditions resulting from the development of autologous antibodies directed against autologous red blood cell antigens resulting in red cell lysis. Beyond the presence, severity, and duration of hemolysis which can lead to symptomatic anemia, additional complications at presentation and during treatment require a high degree of clinical vigilance. These include among others cutaneous, thrombotic, renal disorders, and infectious disorders. Complications can be due to the presence of the pathologic antibody itself, the process of hemolysis, or attributed to treatment. Comprehensive management of AIHA requires awareness and assessment of complications at diagnosis, during, and following treatment.

COVID-19-associated Evans syndrome: A case report and review of the literature.

Evans syndrome is a rare condition characterized by simultaneous or sequential development of autoimmune hemolytic anemia and immune thrombocytopenia (and/or immune neutropenia). Coronavirus disease 2019 (COVID-19) may cause various hematologic conditions, such as coagulation abnormalities (e.g., bleeding or thrombosis) or cell count alterations (e.g., lymphopenia and neutrophilia). COVID-19 may also induce Evans syndrome via immune mechanisms. Here, we describe the case of a patient developing Evans syndrome shortly after COVID-19 infection. Immune thrombocytopenia and warm-type autoimmune hemolytic anemia developed simultaneously, and intravenous immunoglobulin and methylprednisolone were initially administered. Additionally, we intend to review all COVID-19-induced Evans syndrome cases currently present in the literature and emphasize the differences as well as the similarities regarding patient characteristics, relationship to COVID-19 infection, and treatment approach. Since autoimmune cytopenias are frequent in COVID-19 patients, clinicians should pay particular attention to profound and abrupt-onset cytopenias. In these circumstances, hemolysis markers such as lactate dehydrogenase, haptoglobulin, Coombs tests, etc. should be investigated, and the possibility of Evans syndrome should always be considered to ensure prompt and appropriate treatment. These factors are essential to ensure hematologic recovery and prevent complications such as thrombosis.

Severe autoimmune hemolytic anemia following receipt of SARS-CoV-2 mRNA vaccine.

BACKGROUND: Large clinical trials have demonstrated the overall safety of vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, reports have emerged of autoimmune phenomena, including vaccine-associated myocarditis, immune thrombocytopenia, and immune thrombotic thrombocytopenia. CASE PRESENTATION: Here we present a novel case of a young woman who developed life-threatening autoimmune hemolytic anemia (AIHA) after her first dose of a SARS-CoV-2 mRNA vaccine. Notably, initial direct antiglobulin testing was negative using standard anti-IgG reagents, which are "blind" to certain immunoglobulin (IgG) isotypes. Further testing using an antiglobulin reagent that detects all IgG isotypes was strongly positive and confirmed the diagnosis of AIHA. The patient required transfusion with 13 units of red blood cells, as well as treatment with corticosteroids, rituximab, mycophenolate mofetil, and immune globulin. CONCLUSION: As efforts to administer SARS-CoV-2 vaccines continue globally, clinicians must be aware of potential autoimmune sequelae of these therapies.

Cold agglutinin disease and COVID-19 requiring therapeutic plasma exchange.

A 70-year-old man with known cold autoimmune haemolytic anaemia was referred to the emergency department with increased shortness of breath on exertion. He had been confirmed positive for non-variant COVID-19 infection 1 week earlier based on nasopharyngeal swab PCR assay. CT thorax demonstrated diffuse patchy bilateral ground glass opacities, consistent with COVID-19 pneumonia. Bloodwork demonstrated severe cold agglutinin mediated haemolytic anaemia. To help stabilise the patient, he was transferred to a tertiary care hospital for urgent therapeutic plasma exchange. Key supportive therapy included folic acid supplementation, ensuring the patient was kept warm and warmed infusions including transfusions via the apheresis machine. The patient made a good recovery following plasma exchange, and his haemoglobin levels remained stable by discharge.