A Rare Case of Warm Autoimmune Hemolytic Anemia and Massive Splenomegaly in Uncontrolled Grave's Disease

Background: Autoimmune hemolytic anemia (AIHA) occurs when a person's immune system produces autoantibodies that attack their red blood cells, leading to their destruction. Warm AIHA, the most common form of AIHA, is caused by antibodies such as IgG that are active at body temperature. Warm AIHA can be primary or associated with underlying conditions like autoimmune disorders, lymphoproliferative disorders, immunodeficiencies, and infections, due to some form of immune system disruption. Clinical signs include anemia, jaundice, and mild to moderate splenomegaly.

Case Presentation: A 36-year-old man with a history of Graves' disease (GD) (on methimazole) presented with jaundice. Despite being on methimazole, his thyroid levels were uncontrolled due to medication non-adherence, so his outpatient methimazole dose had been increased to 40 mg. Initial labs were notable for the following: a white blood cell count of 1.5 k/mm3, hemoglobin (Hgb) of 5.0 g/dL, platelet count of 78 k/mm3, total bilirubin of 13.1 mg/dL, reticulocyte percentage of 13.1%, lactate dehydrogenase (LDH) of 304 U/L, undetectable haptoglobin, absolute neutrophil count (ANC) of 0.95 k/mm3, thyroid stimulating hormone <0.01 mIU/L and a free T4 of 3.77 ng/dL. CT scan of the abdomen pelvis with contrast showed splenomegaly measuring 24.4 cm. Some reticulocytes were noted on the peripheral smear. The patient was diagnosed with AIHA, with warm antibodies noted on the Coombs test. In terms of workup for the etiology of his AIHA, the following infectious workup was negative: blood parasite smear, HIV, and Lyme enzyme immunoassay. Bone marrow (BM) biopsy flow cytometry showed no immunophenotypic evidence of acute leukemia, non-Hodgkin lymphoma, or high-grade myelodysplasia. He was aggressively transfused with 5 units of PRBCs and started on 1 mg/kg of prednisone daily. He was started on filgrastim 300 mcg 2 times a week for his leukopenia. Post these treatments his hemolysis labs improved to Hgb of 10.4 g/dL, reticulocyte percentage of 4.02%, total bilirubin of 3.1mg/dL, LDH of 141 U/L and haptoglobin of 78 mg/dL. His methimazole was held inpatient due to low ANC count. A trial of lithium was started for GD which led to limited improvement. The patient was discharged on daily prednisone and planned weekly rituximab infusions for AIHA. The patient was discharged without an anti-thyroid agent, with plans for close follow-up outpatient for thyroidectomy vs radioiodine ablation.

Conclusion: The patient's severe Warm AIHA appeared acute, however the massive splenomegaly indicated a chronic low-level hemolytic process. Because the patient did not have any diagnostic findings consistent with hematologic malignancy or infection, and given the context of his recent history, it is reasonable to suspect that this presentation can be attributed to uncontrolled GD. Although the exact pathophysiology of the association is still unclear, the autoimmune nature of GD and hyperthyroidism are thought to contribute to the hemolysis. Warm AIHA is the rarest hematologic manifestation of GD, and literature on the topic has been limited to single case reports. Our case is also unique in that the Warm AIHA was seen in a patient with established GD, and not as an initial presentation of the disorder. To our knowledge, this is also the first case of Warm AIHA with this severe degree of splenomegaly, which can only be explained by the chronic nature of the patient's GD. The response to treatment for AIHA suggests an autoimmune nature of the condition, but the underlying GD did not respond to medical therapy. Overall, this case adds to the literature, as a unique hematologic presentation of an uncontrolled autoimmune disorder.

No relevant conflicts of interest to declare.