December 2022 – Transfusion Medicine

A 53-year-old man diagnosed with Babesia microti two weeks ago status-post atovaquone and azithromycin for one week and clindamycin and primaquine for five days presents with worsening jaundice and anemia. Labs showed: hemoglobin 6.0g/dL (13.3g/dL two weeks ago), total bilirubin 2.6mg/dL, LDH 1855U/L, and reticulocytes 18%. Normal platelets and creatinine. Parasitemia <0.1% by peripheral smear. Direct antiglobulin test 2+ for IgG and 2+ for C3. No recent transfusions. History of pancreatic adenocarcinoma status-post Whipple procedure and splenectomy.

What is the most probable cause of this patient’s worsening anemia?

  • Severe Babesiosis
  • Transfusion reaction
  • Autoimmune hemolytic anemia
  • Drug-induced oxidative hemolysis

The correct answer is ...

Autoimmune hemolytic anemia.

Autoimmune hemolytic anemia is a rare complication of Babesiosis. The onset is two to three weeks after the initial diagnosis. Risk factors include asplenia and immunocompromise. Laboratory findings include decreased hemoglobin, elevated hemolysis labs (i.e., bilirubin, LDH, reticulocytes), and a direct antiglobulin test positive for IgG with or without C3. Cases have been successfully treated with steroids and rituximab. 

Although severe Babesiosis can cause significant hemolytic anemia due to merozoite egress, this patient has been on two weeks of appropriate antimicrobials and has a peripheral smear showing <0.1% parasitemia. In cases of severe Babesiosis, red blood cell exchanges every day until parasite burden is <5% is an ASFA Category II indication.

Drug-induced oxidative hemolysis can occur with primaquine in the setting of G6PD deficiency. In this case, the G6PD status of the patient was not known. However, drug-induced hemolysis has an onset within 24 hours. This patient has been on primaquine for five days, making this diagnosis less likely. 

A delayed hemolytic transfusion reaction can present with elevated hemolysis labs as well as a positive direct antiglobulin test. However, in this case the patient’s history was negative for any recent transfusions. 


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Edwin Lin, M.D., Ph.D.

Resident, Anatomic/Clinical Pathology 
Mayo Clinic

Anand Padmanabhan, M.B.B.S., Ph.D.

Senior Associate Consultant, Hematopathology
Mayo Clinic
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.