Does Eliquis Cause Macrocytosis?
No, Eliquis (apixaban) does not cause macrocytosis. There is no evidence in the medical literature, FDA labeling, or clinical guidelines linking apixaban to macrocytosis (elevated mean corpuscular volume).
Known Hematologic Side Effects of Apixaban
The documented hematologic adverse effects of apixaban are limited to bleeding-related complications:
Bleeding is the primary hematologic concern with apixaban, including gastrointestinal bleeding, intracranial hemorrhage, and other major bleeding events 1, 2.
Thrombocytopenia (low platelet count) is a rare but documented side effect that should be monitored, though it occurs infrequently 3.
Anemia may occur secondary to bleeding complications, which is an indirect effect rather than a direct bone marrow toxicity 2, 4.
Why Macrocytosis is Not Associated with Apixaban
Apixaban's mechanism of action does not affect red blood cell production or maturation:
Apixaban is a direct factor Xa inhibitor that works by selectively blocking the coagulation cascade without interfering with DNA synthesis, vitamin B12 metabolism, or folate pathways—the typical causes of macrocytosis 5.
Unlike warfarin, which affects vitamin K-dependent processes and theoretically could have broader metabolic effects, apixaban has a highly specific mechanism limited to factor Xa inhibition 5, 6.
Clinical Implications
If a patient on apixaban develops macrocytosis, investigate alternative causes:
Evaluate for vitamin B12 or folate deficiency, hypothyroidism, liver disease, alcohol use, or medications known to cause macrocytosis (such as methotrexate, hydroxyurea, or antiretroviral agents).
Consider that macrocytosis may be coincidental or related to underlying conditions (such as chronic kidney disease or cardiovascular disease) rather than the apixaban itself 7.
Do not discontinue apixaban based on macrocytosis alone, as this would remove stroke protection in patients with atrial fibrillation without addressing the actual cause of the elevated MCV 8, 6.
Common Pitfalls to Avoid
Do not attribute all laboratory abnormalities in anticoagulated patients to the anticoagulant itself—many patients on apixaban have multiple comorbidities and medications that are more likely culprits for macrocytosis.
Remember that bleeding from apixaban could lead to reticulocytosis (elevated young red blood cells), which may slightly increase MCV, but this is distinct from true macrocytosis and would be accompanied by anemia and evidence of blood loss 2.