Severe aplastic anemia (SAA) is a rare and life-threatening hematologic disorder characterized by bone marrow failure and pancytopenia, with an incidence of 2–4 cases per million people per year worldwide. Although most cases are idiopathic, infectious agents have been implicated in their pathogenesis. The coexistence of decompensated Chagas cardiomyopathy presents additional challenges, potentially contraindicating treatments such as antithymocyte globulin (ATG) and complicating clinical management. Here, we report a complex case of SAA associated with leptospirosis and chronic Chagas disease in a patient from rural Amazonia, Brazil.

A 64-year-old Black male, retired farmer from Seringueiras (Rondônia, Brazil), with a history of ischemic stroke (2018), deep vein thrombosis (2023), uncontrolled hypertension, and untreated chronic Chagas disease, was admitted in April 2025 with severe pancytopenia and systemic symptoms (fatigue, diffuse myalgia, intermittent fever, exertional dyspnea, orthopnea, and lower limb edema). He had recently received four units of packed red blood cells. On admission, he reported VAS 9/10 pain and denied bleeding or mucocutaneous lesions. Environmental exposures included rodents, ticks, and agrochemicals. Initial differential diagnoses included leptospirosis, Lyme disease, Chagas reactivation, and heart failure with preserved ejection fraction. Empirical ceftriaxone was started, and erologic tests, imaging, and cardiac markers were ordered. The case was referred for multidisciplinary evaluation. Leptospira IgM/IgG was positive, and additional leptospira antibody testing was requested; T. cruzi parasitemia was negative. Transthoracic echocardiogram showed systolic dysfunction (EF 35%), eccentric hypertrophy, biatrial enlargement, moderate mitral and tricuspid regurgitation, and estimated PASP of 40 mmHg. BNP was elevated, confirming heart failure with reduced ejection fraction (HFrEF). On day 2, the patient reported 60% symptom relief, but later worsened. Hematology suspected acute leukemia, marrow aplasia, or myelophthisis. Aspiration revealed marked hypoplasia with fatty replacement. Biopsy confirmed severe aplastic anemia without dysplasia or malignant infiltration. Due to cardiac dysfunction, ATG was contraindicated. Immunosuppressive therapy with cyclosporine (100 mg BID) and eltrombopag (150 mg/day) was initiated, along with transfusional support and prophylactic antimicrobials. The patient initially showed clinical stability, but pancytopenia and systemic inflammation (CRP > 200 mg/L) persisted. Although T. cruzi PCR was negative, the presence of Chagas cardiomyopathy and the use of immunosuppressive therapy raised concern for potential Chagas reactivation. Due to the high cost of immunosuppressive therapy, transfer to a referral center in the public health system (SUS) was requested.

In chronic Chagas disease, immunosuppression poses a serious risk of reactivation, demanding proactive and stringent surveillance.