Background: Severe anemia is a common medical emergency causing impaired oxygen delivery to vital tissues and organs. Prompt recognition, diagnosis, and management of anemia is vital to restore adequate tissue perfusion and prevent downstream complications. Severe anemia, defined by hemoglobin (Hb) <8.0 g/dL, and life-threatening anemia by Hb <6.5 g/dL, is treated with RBC transfusion. However, some patients cannot receive transfusions due to religious beliefs, most notably Jehovah's Witnesses. This creates a unique clinical challenge and highlights the importance of utilizing other methods to rapidly correct anemia. Previous studies have focused on preoperative optimization in this patient population, but data on emergent management remain limited.

Objective: Evaluate clinical outcomes following administration of epoetin alfa (EPO) and intravenous (IV) iron in patients with critical anemia who decline blood transfusion for religious reasons.

Methods: We performed a retrospective single-arm observational study using data from Montefiore Medical Center's electronic health records from 2016 to 2025. Patients with severe anemia who both declined blood transfusion for religious reasons and were treated with EPO at a dose of 20,000 to 40,000 for at least three consecutive days were included for analysis. Patients who concurrently received EPO for chronic anemia related to CKD or malignancy or who had other transfusion contraindications, including alloimmunity to blood products or hemolytic anemia, were excluded. The primary outcome of analysis was time to hemoglobin recovery defined as Hb >8 g/dL or an absolute Hb increase >2 g/dL from treatment initiation. Secondary outcomes included peak Hb, time to peak Hb, and in-hospital mortality. For patients who did not recover during the index hospitalization but did show recovery at a follow-up visit, the date of first follow-up appointment showing recovery was assigned as the time of hemoglobin recovery.

Results: Of 135 patients screened, 66 met inclusion criteria. Median age was 70 years and the population skewed 64% female. Acute anemia was present in 54.5% of patients, while 45.5% had acute on chronic anemia. Acute blood loss was the cause of anemia in 74% of cases with the remainder attributed to subacute bleeding or chronic inflammatory conditions.

Hemoglobin recovery occurred in 74% of the examined population, of which 31 (63%) recovered during the index admission and 18 (37%) were seen to have met recovery on repeat laboratory work performed at a follow-up appointment. Median time to recovery was 13 days overall. The median increase in Hb was 4.4 g/dL and the median peak Hb, defined as within 90 days of treatment, was 9.7 g/dL. For the 31 patients who recovered during admission, the median time to peak hemoglobin was 31 days. Most patients (88%) received concomitant IV iron; there was no statistically significant difference in Hb recovery in the patients for which iron was deferred (p=0.664). The most common reason for iron deferral was hyperferritinemia. Among the 17 non-recovered patients, 35% died during hospitalization. Overall, in-hospital mortality was 14%. One thrombotic event occurred post EPO.

Conclusions: This study represents the first evaluation of EPO and IV iron treatment outcomes in an emergent setting for patients who decline blood transfusions. Our data demonstrate that this approach is a feasible alternative to transfusion, as evidenced by a 74% hemoglobin recovery rate with a median increase in Hb of 4.4 g/dL. However, approximately 1 in 4 patients did not recover, and overall mortality remained significant at 14%, underscoring EPO and IV iron therapy as a second-line option after transfusion. Overall, further prospective studies are warranted to clarify safety, optimize dosing and route of administration, and better define the role of IV iron therapy across clinical settings.

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2025
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