Case Presentation: A 70-year-old male with a past medical history of nephrotic syndrome secondary to anti-phospholipase A2 receptor (anti-PLA2R) associated membranous nephropathy presented with acute, progressive dyspnea. Exam was notable for pallor and his admission hemoglobin was 4.8. Initial labs also showed WBC 2.9, platelets 104, LDH 724, ferritin 2,215, Creatinine 1.8. Blood smear remarkable for 1+ schistocytes. Patient was initially treated for Thrombotic Thrombocytopenic Purpura (TTP) secondary to anti-PLA2R membranous nephropathy with a course of plasma exchange and prednisone (1mg/kg). Platelet count continued to decrease despite treatment for 9 days. ADAMS13 panel returned normal, ruling out TTP and atypical Hemolytic Uremic Syndrome (aHUS) was then considered. Eculizumab was initiated and the following day the patient developed a fever. Another blood smear was sent and returned positive for parasitemia with the patient testing positive for Babesia shortly after. Patient was treated with 17 days of Azithromycin 500mg daily and Atovaquone 750mg BID with normalization of hemoglobin and platelets and resolution of all symptoms.
Discussion: Babesiosis, caused by the parasite Babesia microti, is a tick-borne disease transmitted by the Blacklegged tick Ixodes scapularis. Upon transmission the parasite invades and replicates within erythrocytes. Babesiosis typically presents with non-specific febrile illness, myalgia and arthralgia. Splenomegaly and jaundice may also be seen. Anemia is found in up to 76.5% of patients. There are several mechanisms through which babesiosis can cause a microangiopathic hemolytic anemia. Parasite burden can directly result in erythrocyte rupture and hemolysis. Alternatively, infected erythrocytes produce elevated levels of reactive oxygen species leading to oxidative damage with eryptosis and programmed red blood cell death. Infected erythrocytes also enhance outer membrane phosphatidylserine concentration, identifying these cells for programmed cell death. Finally, molecular mimicry between the babesia thrombospondin protein component BMP53 and host platelets can result in autoimmune destruction of platelets and erythrocytes.A diagnosis of babesiosis is confirmed with identification of intraerythrocytic parasites on peripheral blood smear. However, low parasite burden can make observation of intraerythrocytic and extraerythrocytic parasites difficult to observe. The Infectious Disease Society of America and the American Society for Microbiology recommend manual screening of both thick and thin blood smear samples. A minimum of 100 microscopic fields examined using 100x objective are recommended prior to reporting a negative diagnosis. This patient required multiple smears to discover his parasitemia, delaying the correct diagnosis and leading to alternative diagnosis and treatments instead.
Conclusions: This case demonstrates that babesiosis should be considered in the differential diagnosis of microangiopathic hemolytic anemia. In cases of microangiopathic hemolytic anemia in which the diagnosis is unclear, the proper technique of microscopic examination is crucial to ensuring a diagnosis of babesiosis is not missed. When initial treatment is not effective for microangiopathic hemolytic anemia, re-evaluation of the blood smear is appropriate.