Can Plaquenil (hydroxychloroquine) cause anemia?

Hydroxychloroquine (Plaquenil) and Anemia

Yes, hydroxychloroquine (Plaquenil) can cause anemia, particularly hemolytic anemia in patients with G6PD deficiency, though this is rare. The FDA drug label specifically lists hemolytic anemia as a potential adverse effect that should be monitored, especially in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency 1.

Types of Anemia Associated with Hydroxychloroquine

Hydroxychloroquine may cause several types of hematologic effects:

• Hemolytic anemia: Particularly in patients with G6PD deficiency, though recent research suggests this risk may be lower than previously thought 1, 2
• Myelosuppression: Hydroxychloroquine can cause bone marrow suppression leading to aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia 1
• General hematologic toxicity: The FDA label specifically mentions that blood cell counts should be monitored periodically in patients on prolonged hydroxychloroquine therapy 1

Risk Factors and Monitoring

Certain patient populations may be at higher risk for developing anemia while on hydroxychloroquine:

• G6PD deficiency: Traditionally considered a risk factor, though recent studies show limited evidence of clinical hemolysis in these patients 2, 3
• Long-term therapy: Patients on prolonged hydroxychloroquine therapy should have periodic blood cell count monitoring 1
• Concomitant medications: Patients taking other medications that may cause anemia could have additive effects 4

Evidence on Hydroxychloroquine and Hemolytic Anemia in G6PD Deficiency

Despite traditional concerns, recent research provides interesting insights:

• A 2022 study found no evidence of hemolysis in G6PD-deficient patients exposed to hydroxychloroquine, despite more than 500 months of cumulative exposure time 2
• Another study examining 11 G6PD-deficient patients (all African American) found no episodes of hemolysis during more than 700 months of hydroxychloroquine exposure 3
• These findings suggest that the risk of hemolytic anemia with hydroxychloroquine in G6PD-deficient patients may be lower than previously thought, particularly in those with the African variant of G6PD deficiency 2, 3

Clinical Approach

For patients on hydroxychloroquine therapy:

• Baseline assessment: Consider checking complete blood count before initiating therapy 1
• Regular monitoring: Periodic blood cell counts for patients on long-term therapy 1
• Symptom awareness: Monitor for signs of anemia including fatigue, pallor, shortness of breath, or weakness 1
• G6PD testing: While the American College of Rheumatology does not recommend routine G6PD testing before hydroxychloroquine initiation, the FDA label does recommend careful use in patients with known G6PD deficiency 2

Management of Suspected Hydroxychloroquine-Induced Anemia

If anemia develops in a patient on hydroxychloroquine:

• Evaluate for hemolysis: Check reticulocyte count, haptoglobin, LDH, and bilirubin levels 1
• Consider drug discontinuation: If myelosuppression cannot be attributed to the underlying disease, discontinue hydroxychloroquine 1
• Monitor recovery: After discontinuation, monitor blood counts for improvement 1

Important Caveats

• The risk of anemia appears to be dose-dependent, with higher doses carrying greater risk 4
• Anemia may be multifactorial in patients with autoimmune conditions, with disease activity also contributing 4
• Patients with renal impairment may be at higher risk due to reduced drug clearance 1

While hydroxychloroquine can cause anemia through various mechanisms, careful monitoring and appropriate patient selection can minimize this risk. The evidence suggests that hemolytic anemia in G6PD-deficient patients may be less common than previously thought, but vigilance is still warranted 2, 3.