Abstract Background Coinfection with Borrelia burgdorferi and Babesia microti presents a diagnostic challenge in endemic regions. Positive Lyme serology may lead to anchoring bias and delayed recognition of babesiosis, permitting progression to severe intravascular hemolysis and cardiopulmonary compromise. Case Presentation A 72 years old woman with type 2 diabetes mellitus, hypertension, and hypothyroidism presented with one month of progressive fatigue, dyspnea, weakness, intermittent low-grade fever, and a non erythema migrans macular rash. Initial outpatient hemoglobin was 9 g/dL. Lyme serology returned positive and doxycycline was initiated. She later developed worsening dyspnea and weakness and presented to the hospital.On arrival, temperature was 38.6 °C, oxygen saturation 87 percent on room air, respiratory rate 25 breaths per minute, and blood pressure 106/49 mm Hg with evolving shock requiring vasopressor support. Hemoglobin declined to 6.7 g/dL, lactate dehydrogenase was 1,000 U/L; haptoglobin 10 mg/dL; platelets were normal. Reticulocyte count was 2.33 percent with a reticulocyte index of 4.6. Thin blood smear demonstrated intraerythrocytic parasites with Maltese-cross tetrads, and thick smear confirmed parasitemia. Polymerase chain reaction identified Babesia microti and parasitemia was quantified at 4.6 percent. Other tick-borne pathogens were excluded. Chest imaging showed no infiltrates, consistent with hypoxemia due to reduced oxygen-carrying capacity rather than primary lung disease. She received two units of packed red blood cells and atovaquone, azithromycin, with continuation of doxycycline. By hospital Day 3, dyspnea and fever improved, oxygenation normalized, and symptoms continued to resolve. Discussion This case highlights the complexity of tick borne co-infection and the risk of anchoring bias after positive Lyme serology. Because doxycycline has no activity against Babesia microti, clinical deterioration during treatment should prompt immediate evaluation for babesiosis. Thin blood smear remains the primary diagnostic tool for identifying babesial morphology, while thick smear enhances sensitivity and enables accurate parasitemia quantification, a critical yet often overlooked step in severe disease. Demonstration of 4.6 percent parasitemia reflected significant burden and guided management, including close monitoring for possible exchange transfusion. Conclusion In endemic regions, babesiosis should be considered when patients with Lyme disease develop hemolysis or clinical decline. Combined thin and thick smear evaluation and parasitemia quantification are essential for timely diagnosis, risk stratification, and prognostication. This abstract is funded by: N/A
D Zoarob (Fri,) studied this question.