Cold agglutinin-mediated autoimmune haemolytic anaemia associated with diffuse large B cell lymphoma

Abstract

Cold agglutinin-mediated autoimmune haemolytic anaemia is associated with the development of autoantibodies that can agglutinate red blood cells at cold temperatures. While primary cold agglutinin disease is an idiopathic lymphoproliferative disorder, secondary cold agglutinin syndrome (CAS) complicates other diseases such as infections, autoimmune diseases and cancers, mostly low-grade lymphomas. Early recognition, treatment of CAS and treatment of its associated underlying diseases are crucial to a successful outcome. We report a case of CAS in a setting of diffuse large B cell lymphoma, in which the treatment course was complicated by worsened anaemia due to chemotherapy-induced myelosuppression. We reviewed previously reported cases and discussed diagnosis and treatment strategies, including novel complement inhibitors, as potential future therapy.

Keywords: haematology (drugs and medicines); malignant and benign haematology; malignant disease and immunosuppression.

Figure 1

H&E staining of peripheral blood smear. (A) x50 magnification, (B) x100 magnification. Peripheral blood smear shows anisopoikilocytosis with spherocytes, red blood cell agglutination and nucleated red cells. (C) H&E staining of lymph node biopsy shows large mononuclear cell infiltration, confirmed by immunohistochemical staining to be positive for CD20, CD10, CD45, BCL6, BCL2 and MUM1, compatible with diffuse large B cell lymphoma. (D) Staining for Ki67 shows near 100% expression suggesting for highly proliferative tumour. H&E staining of bone marrow aspirates: (E) x20 magnification, (F) x100 magnification. The bone marrow aspirates reveal hypercellular marrow with both erythroid and myeloid hyperplasia, with left shift. There was no evidence of bone marrow involvement by diffuse large B cell lymphoma.