Severe Babesiosis With Multifactorial Hemolysis and Pulmonary Complications in an Asplenic Patient at a Tertiary Cancer Center

Babesiosis is a tick-borne protozoal infection that can cause life-threatening disease in asplenic or immunocompromised patients. We report a 71-year-old woman with prior distal pancreatectomy and splenectomy who developed severe babesiosis complicated by pulmonary involvement and complement-mediated hemolysis. Initial therapy with clindamycin-atovaquone and partial exchange transfusion was required due to a reported azithromycin allergy; following successful rechallenge, she tolerated guideline-based azithromycin-atovaquone. Despite parasite clearance, she developed complement-mediated hemolysis confirmed by a complement C3-positive, IgG-negative direct antiglobulin test. A 71-year-old woman with a history of distal pancreatectomy and splenectomy for pancreatic carcinoma (without recurrence) presented from upstate New York with one week of fever, chills, headache, fatigue, and myalgias. She denied a known tick bite but reported a small pink skin lesion. Initial laboratory evaluation revealed thrombocytopenia, transaminitis, and hyperbilirubinemia; hepatitis, Epstein-Barr virus, and cytomegalovirus testing were negative, while <i>Babesia microti</i> polymerase chain reaction (PCR) was positive. Because of a reported azithromycin allergy manifesting as hives, she was started on clindamycin-atovaquone. On admission to Memorial Sloan Kettering Cancer Center, her hemoglobin was 7.6 g/dL, lactate dehydrogenase (LDH) 392 U/L, and parasitemia 9.7%. Partial exchange transfusion (four of nine units) lowered parasitemia to 5.2%. The clinical course was complicated by recurrent fevers, hypotension, and hypoxia requiring a high-flow nasal cannula; chest CT demonstrated bilateral ground-glass opacities and pleural effusions. On hospital day 10, an azithromycin challenge was tolerated, and therapy was transitioned to azithromycin-atovaquone, with parasitemia clearing by day 16. Despite clearance of parasitemia, the patient developed worsening hemolysis characterized by a complement C3-positive, immunoglobulin (IgG)-negative direct antiglobulin test, consistent with complement-mediated hemolysis; cold agglutinin titer was negative. She experienced a hemoglobin nadir of 6.5 g/dL, lactated dehydrogenase peaking at 1,573 U/L, haptoglobin <8 mg/dL, and mild transient elevations in liver enzymes. She required multiple transfusions, though immunosuppressive therapy was avoided, and hematologic parameters improved as the infection resolved. Echocardiography revealed preserved systolic and diastolic function with a left ventricular ejection fraction of 68%. This case highlights several important aspects of severe babesiosis. First, asplenic patients represent a high-risk population, prone to higher parasitemia and serious complications. Second, therapeutic challenges may arise in the setting of drug allergies, but careful reevaluation can allow the use of guideline-based azithromycin-atovaquone therapy. Third, this case underscores the emerging recognition of complement-mediated autoimmune hemolysis in babesiosis, demonstrated by worsening hemolysis despite parasite clearance and a complement C3-positive, immunoglobulin G (IgG)-negative direct antiglobulin test. Finally, optimal outcomes required a multidisciplinary approach involving infectious disease, hematology, and transfusion medicine specialists, reflecting the complexity of management in severe and atypical babesiosis.