Can Rituximab Cause Hemolytic Anemia?
Yes, rituximab can cause hemolytic anemia, though this is a rare adverse effect documented in the FDA label and clinical literature. 1
Direct Evidence from FDA Drug Label
The FDA label for rituximab explicitly documents hemolytic anemia as an adverse reaction:
- Two occurrences of hemolytic anemia were reported following rituximab therapy during single-arm studies 1
- One case of transient aplastic anemia (pure red cell aplasia) also occurred 1
- Anemia was reported in 3% of patients with NHL receiving rituximab monotherapy as a Grade 3-4 cytopenia 1
Mechanism and Clinical Context
Rituximab-induced hemolytic anemia can occur through immune-mediated mechanisms:
- The drug may trigger autoimmune hemolytic anemia as an immune-related adverse event, particularly in the context of immune dysregulation 2
- This represents a paradoxical immune response where an immunosuppressive agent triggers autoimmune hemolysis 3
Important Clinical Distinction
Rituximab is more commonly used to TREAT hemolytic anemia rather than cause it:
- Rituximab is indicated for immune hemolytic anemia unresponsive to corticosteroids in Waldenström macroglobulinemia 2
- Multiple case reports demonstrate successful treatment of severe autoimmune hemolytic anemia (both warm and cold antibody types) with rituximab 4, 5, 6, 7, 8
- The American Society of Hematology recommends rituximab as part of immunosuppressive therapy for hemolytic transfusion reactions in sickle cell disease 2
Risk Assessment and Monitoring
When rituximab is administered, monitor for:
- Complete blood count with differential to detect developing anemia 1
- Direct antiglobulin test (Coombs test), haptoglobin, and LDH if hemolysis is suspected 2
- Reticulocyte count and peripheral blood smear for evidence of hemolysis 2
- Signs of hemolysis including jaundice, dark urine, and unexplained fatigue 2
Clinical Caveat
The incidence of rituximab-induced hemolytic anemia is extremely low compared to its therapeutic benefit in treating autoimmune hemolytic conditions 1, 4, 5. When hemolytic anemia occurs in patients receiving rituximab, consider alternative etiologies including underlying disease, concomitant medications, or transfusion-related reactions before attributing it solely to rituximab 2, 3.