Severe hemolysis flare of refractory autoimmune hemolytic anemia with positive complement component C3d responsive to Iptacopan with cyclophosphamide and prednisone: a case report

CHILDHOOD REFRACTORY AUTOIMMUNE HAEMOLYTIC ANAEMIA: IS THERE A ROLE FOR ANTI‐CD20 THERAPY (RITUXIMAB)?

Diagnosis and management of Evans syndrome in adults: first consensus recommendations

Alemtuzumab for Treatment of Refractory Evans Syndrome

Autoimmune Hematologic Disorders in Two Patients After mRNA COVID-19 Vaccine

A 58-year old man with a history of hypothyroidism and primary antiphospholipid syndrome (with recurrent thromboembolic disease and therapy-refractory autoimmune thrombocytopenic purpura) presented with a life-threatening crisis of warm autoimmune hemolytic anemia (AIHA) while under chronic low-dose steroid therapy. The exacerbation was eventually controlled with a 5-day course of intravenous immunoglobulin (IVIG, Sandoglobulin) (400 mg/kg per day) but hemolysis rapidly recurred, despite therapy with steroids, azathioprine, and cyclosporin, necessitating a second course of IVIG. Control of packed cell transfusion needs for about 7 months was achieved by weekly administration of IVIG (800 mg/kg), although there is no direct evidence that IVIG therapy reduced the production of anticardiolipin or RBC antibodies. Three months after discontinuation of IVIG and change to maintenance with intermediate-dose corticosteroids plus cyclosporin A, the patient succumbed to duodenal perforation with peritonitis and invasive pulmonary aspergillosis. The case illustrates that IVIG therapy may be helpful in selected life-threatening and refractory cases of AIHA. It also sadly illustrates the long-term toxicity of standardly used therapeutics in refractory AIHA.

Objective: To investigate the significant of peripheral CD(4)(+) CD(69)(+) T lymphocytes in patients with autoimmune hemolytic anemia (AIHA)/Evans syndrome (ES). Methods: In this study peripheral blood samples from 32 patients with AIHA/ES (15 hemolytic episode patients, 17 remission patients) and 13 healthy controls were collected. Patients with AIHA/ES were recruited in Tianjin Medical University General Hospital from October 2015 to May 2016. The percentages of CD(69)(+) T lymphocytes were analyzed by flow cytometry. The expression of CD(69) mRNA in CD(4)(+) T lymphocytes which was sorted from peripheral blood by magnetic activated cell sorting (MACS) was detected using real-time PCR. Soluable CD(69) was measured by ELISA. Results: In hemolytic episode patients, the ratio of CD(3)(+)CD(69)(+)/CD(3)(+)T lymphocytes [(3.08±1.48)%] was significantly higher than that in healthy controls [(1.28±0.83)%, P<0.01] and in remission group[(1.96±1.33)%, P<0.05]. The absolute count of CD(3)(+)CD(69)(+)T lymphocytes in hemolytic episode group [(2.94±1.81)×10(7)/L] was higher than that in healthy controls [(1.48±1.42)×10(7)/L, P<0.05]. The ratio of CD(3)(+)CD(4)(+)CD(69)(+)/CD(3)(+)CD(4)(+)T cells in hemolytic episode group [(2.16±1.56)%] was significantly higher than that in remission group [(1.16±0.62)%, P<0.05] and healthy controls[(0.94±0.78)%, P<0.05]. The quantity of CD(3)(+)CD(4)(+)CD(69)(+)T lymphocytes in hemolytic episode group[(1.04±0.98)×10(7)/L] was higher than in healthy controls [(0.44±0.38)×10(7)/L, P<0.05]. The ratio of CD(3)(+)CD(8)(+)CD(69)(+)/CD(3)(+)CD(8)(+)T lymphocyte in hemolytic episode group [(4.87±2.56)%] was significantly higher than that in healthy controls[(1.83±1.27)%, P<0.01]. The quantity of CD(3)(+)CD(8)(+)CD(69)(+)T lymphocytes in three groups did not show significant difference. The ratio of CD(3)(+)CD(4)(+)CD(69)(+)/CD(3)(+)CD(4)(+) T lymphocytes in hemolytic episode group was negatively correlated with hemoglobin (Hb) (P<0.01) , positively correlated with the percentage of reticulocytes (Ret%) (P=0.01) total bilirubin(TBil), indirect bilirubin(IBil) (P<0.01) and not correlated with absolute reticulocytes count, lactic dehydrogenase (LDH), complement 3(C3), complement 4 (C4). The ratio of CD(3)(+)CD(4)(+)CD(69)(+)/CD(3)(+)CD(4)(+)T lymphocytes in remission group was negatively correlated with Hb (P<0.05). In hemolytic episode patients CD(69) mRNA (32.26±35.11) was significantly higher than that in remission group(6.05±5.87) (P<0.05) and healthy controls (1.76±1.85)(P<0.01). CD(69) mRNA in remission group was significantly higher than healthy controls (P<0.05). Serum CD(69) in hemolytic episode patients [(494.21±16.06) ng/L] was significantly higher than that in healthy controls [(441.39±104.6) ng/L, P<0.05]. Conclusion: Our findings suggest that the proportion of CD(4)(+)CD(69)(+) T lymphocytes increase in AIHA/ES patients, which is correlated with the severity of disease.

Epidemiology of autoimmune hemolytic anemia: A nationwide population-based study in France.

Real-world evidence from China: Clinical characteristics, treatment landscape and long-term outcomes in 566 autoimmune hemolytic anemia patients

Pediatric Autoimmune Hemolytic Anemia Is Associated with a High Incidence of an Underlying Immune Disorder and High Mortality Rate

The Epidemiology of Hemoglobin Levels in Patients With Type 2 Diabetes

Evans Syndrome: A Systematic Review

The Safety of Repurposing Daratumumab for Relapsed or Refractory Autoimmune-Antibody-Mediated Hemolytic Anemia

Autoimmune hemolytic anemia is thought to be mediated via auto-antibodies produced by lymphoid B cells. This may be an idiopathic process or secondary to an underlying infection or lymphoproliferative disorder. Conventional treatment comprises immunosuppression with corticosteroids and, in some cases, splenectomy. A proportion of patients require lifelong immunosuppression to maintain disease remission. Monoclonal antibody rituximab has gained widespread acceptance in the management of B-cell malignancies. Additionally, it has been used to treat disorders associated with auto-antibody production, such as cold hemagglutinin disease, immune thrombocytopenia, and Evans syndrome. Its use in the treatment of patients with autoimmune hemolytic anemia in the setting of allogeneic bone marrow transplantation as well as in patients with an underlying lymphoproliferative disease has also been reported. We report herein the successful use of rituximab in the treatment of two patients with idiopathic refractory warm autoimmune hemolytic anemia, who are still in remission at 15 and 9 months following treatment.

Use of Eculizumab in a Patient with Refractory Autoimmune Hemolytic Anemia with Heterozygous NFκB1 Mutation

Autoimmune Hemolytic Anemia during Pregnancy or Post-Partum: An International Multi-Center Experience