Abstract
Autoimmune hemolytic anemia (AIHA) is a rare form of anemia with an incidence of 1-3 cases per 100,000 per year. AIHA can be subclassified into warm, cold, mixed, and DAT-negative AIHA based on findings of the direct antiglobulin test (DAT). Furthermore, AIHA can be primary, or secondary to other disorders, though data on the prevalence of secondary diseases is limited. To better define these issues, we conducted a retrospective analysis of all patients with AIHA treated at the Cleveland Clinic from January 2000 to April 2013.
Patients were included if they were ≥ 18 years old and presented with either a new diagnosis or relapsed AIHA, defined as a hemoglobin level < 10 g/dL with a positive DAT and laboratory evidence of hemolysis (at least one of following present: elevated reticulocytes, bilirubin or LDH, or low haptoglobin). Patients with a negative DAT were included if other causes of hemolytic anemia were excluded. Frequencies of primary and secondary AIHA were recorded. We also determined the prevalence of disorders commonly associated with AIHA, including infection, autoimmune disease, hematologic malignancies, monoclonal gammopathy, organ transplant, recent transfusion and pregnancy. Differences between warm and cold AIHA were analyzed using Fisher’s exact test.
A total of 180 patients were identified, with 83 (46%) males and 97 (54%) females. 133 (74%) patients presented as a new diagnosis and 47 (26%) presented with relapse. 109 (61%) of patients were in the 50-80 year age range, and 146 (81%) of patients were Caucasian. 122 (69%) patients had warm AIHA, 42 (24%) cold AIHA, 6 (3%) mixed AIHA, and 8 (4%) DAT negative AIHA. AIHA was considered primary in 28% of patients with warm AIHA, 12% with cold AIHA, 50% with mixed AIHA, and in none of the patients with DAT negative AIHA. Of patients with warm antibody-mediated secondary AIHA (n = 122), most presented with either autoimmune disease (24%) or a hematologic malignancy (27%), while other less common associations included infection (3%), monoclonal gammopathy (11%), organ transplant (3%), recent blood transfusion (4%), pregnancy (1%), and Evan’s syndrome (15%). There was a higher frequency of both hematologic malignancies and monoclonal gammopathies in the cold antibody-mediated AIHA patients (45% vs. 27%, p = 0.04, and 45% vs. 11%, p < 0.0001). The proportions of patients with CLL (16% vs. 19%) and non-CLL NHL (8% vs. 5%) were similar (p =.63, .73, respectively). Low grade lymphoproliferative disorders were common in the cold AIHA group (10%) but not present in patients with warm antibody-mediated AIHA (p=.004). The proportions of patients with autoimmune disease (29%), organ transplant (2%), and blood transfusions (5%) were similar in patients with cold and warm antibody AIHA (all p>.54), while fewer patients with cold AIHA developed Evan’s syndrome (2%; p=0.05). In the DAT negative group (n = 8), 4 (50%) of the patients presented with hematologic malignancy, one patient had an autoimmune disease, one had a monoclonal gammopathy and two had Evan’s syndrome.
These results demonstrate the high frequency of both autoimmune disorders and hematologic malignancies in patients with AIHA, while other associated disorders, such as viral illnesses, were less common. Cold antibody-mediated AIHA was associated with a higher prevalence of other hematologic disorders than warm antibody-mediated AIHA, in particular low grade lymphoproliferative disorders and monoclonal gammopathy.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
