Autoimmune hemolytic anemia: An underrecognized contributor to anemia and hemolysis in babesiosis infection Free

Background: Babesiosis is a zoonotic illness transmitted by ticks and caused by intraerythrocytic protozoa belonging to the genus Babesia. It is endemic to Connecticut with approximately 216 cases reported annually, and on the rise due to a host of factors including climate change. The elderly, immunocompromised and those who have undergone splenectomy are at greatest risk of severe illness from babesiosis. Post-babesiosis autoimmune hemolytic anemia (AIHA) has been described as a consequence of babesiosis. Despite the association, direct antiglobulin test (DAT) is not routinely performed during hemolysis with babesiosis infection. It remains unclear whether there is a correlation between parasitemia burden and degree of anemia, and therefore would warrant further evaluation for AIHA and subsequent AIHA directed therapy in addition to antimicrobials for babesiosis treatment. Therefore, the objective of this analysis was 1. Describe the prevalence and clinical features of post-babesiosis AIHA (+DAT); 2. Identify the association of parasitemia and degree of anemia and hemolysis

Methods: We performed an IRB-approved retrospective electronic medical record analysis of patients admitted to Yale New Haven Hospital from January 1, 2013 to December 31, 2023, with a primary diagnosis of babesiosis (N= 406). Demographics, splenectomy status, parasite load (smear %), Lyme co-infection, hemoglobin (Hgb; initial and nadir), markers of hemolysis (lactate dehydrogenase and haptoglobin), DAT, antibiotic regimen, blood product transfusion, including RBC exchange were recorded. Independent samples t-test and chi-squared test were used for statistical analysis when comparing means and categorical outcomes, respectively.

Results: Data was analyzed for 406 patients. Median age was 73 (range 2 to 103) with a male predominance (67.5%; 264/406). Asplenia was seen in10.7% (42/406), and 32.5% (127/406) had Lyme-coinfection. DAT was performed in 88 patients (21.5%) with a positive screen in 20 (4.9%), consistent with post-babesiosis AIHA. Those with post-babesiosis AIHA had a lower Hgb at presentation (9.03 g/dL vs 10.65 g/dL) and nadir (7.12g/dL vs 8.9 g/dL). The degree of hemolysis was greater in patients with AIHA regardless of parasitemia compared to without AIHA (LDH 1203.8 vs 687.5). Most received the standard antibiotic regimen of atovaquone, azithromycin and doxycycline. Those with AIHA were treated with RBC transfusion and RBC exchange with more frequency compared to those without AIHA (70% vs 32%; 35% vs 10.5%).Parasitemia burden was inversely correlated with Hgb, and directly correlated with markers of hemolysis. Lyme co-infection had no effect on anemia or hemolysis.

Discussion: This retrospective study of patients with babesiosis at a single tertiary care center over a 10-year period highlights important clinical correlations between parasitemia, anemia, hemolysis, and the presence of post-babesiosis AIHA. Our findings are the first to show the correlation of anemia and hemolysis with parasite load. Furthermore, for the first time we show the relationship between post-babesiosis AIHA, anemia and hemolysis, resulting in increased need for RBC transfusion and RBC exchange, indicating its contribution to clinical severity and therapeutic complexity. Despite the relatively low number of patients undergoing DAT testing, the detection rate of AIHA was notable, pointing to potential diagnostic underutilization. These findings suggest that AIHA may be an under-recognized complication of babesiosis, particularly in patients with anemia out of proportion to parasitemia. Routine DAT testing in patients with babesiosis may help identify those who would benefit from additional immunomodulatory therapies alongside antimicrobial treatment.