Occurrence of cold agglutinin disease among patients with autoimmune hemolytic anemia- a Hungarian single-center experience

Introduction: Cold agglutinin disease is a rare autoimmune hemolytic anemia, a low-grade lymphoproliferative disease. Our objective was to determine the occurrence of cold agglutinin disease among patients with autoimmune hemolytic anemia and to map its specific characteristics, with a particular focus on thromboembolic complications. Methods: In a Hungarian hematology center, we retrospectively studied clinical data, laboratory parameters, and therapy of 84 patients with autoimmune hemolytic anemia. Results: 17% of patients had cold autoimmune hemolytic anemia, with eight patients fulfilling the criteria for cold agglutinin disease and seven patients having cold agglutinin syndrome. Most patients were older than 70 years, and the disease was more common in women (49 women, 35 men). 71% of patients with CAD were administered rituximab, while some received additional chemotherapy. The 10-year survival rate was significantly worse in cold-type hemolytic anemia than in warm-type autoimmune hemolytic anemia (66.7% vs. 82.4%). Congenital and acquired causes of thrombophilia were examined in patients with severe hemolysis (hemoglobin <60 g/l, LDH >1.5x the upper limit of normal) and in cases with thromboembolic complications. Conclusion: This is the first case series from a country in Central Eastern Europe with a four-season climate, demonstrating the occurrence of cold autoimmune hemolytic anemia. Overall survival was influenced by age, type of hemolytic anemia, and total bilirubin level during presentation. Inherited and acquired thrombophilia risk factors and antiphospholipid antibodies were detected in more patients with cold autoimmune hemolytic anemia than those with warm autoimmune hemolytic anemia.