In this open-label study, eligible and consenting adult patients admitted to the hospital for critical care that have acute severe anemia, defined as a blood hemoglobin level ≤ 5 g/dL, but who are unwilling or unable to receive red blood cell (RBC) transfusion, will receive one or more infusions of SANGUINATE as are deemed necessary by the Investigator for survival of the acute anemic episode.

Data collection for each patient during the in-patient portion of the study will be required for up to a maximum of 14 days while under critical care, with additional collection of safety-related findings at 7 days and 14 days after the last infusion of SANGUINATE. Each patient will thus have up to 28 days participation in the trial.

A minimum of 100 subjects are to be enrolled and to receive at least one infusion of SANGUINATE, with 14-day follow-up after the last infusion.

Because of the life-threatening effects of severe anemia, it is expected that all patients in this trial will receive care within a critical care facility (may be called intensive care or some similar name), wherein all patients will have real-time monitoring of vital signs and ECG (e.g., by telemetry) before, during, and after all study drug infusions.

Inclusion Criteria:

1. The patient would otherwise receive RBC transfusion for treatment of severe anemia but cannot (hemolytic/allosensitized or no compatible blood) or will not (religious/personal objection) receive RBCs
2. Hemoglobin ≤ 5 g/dL, or hemoglobin ≤ 7 g/dL following a decline of ≥ 5 g/dL over less than 7 days
3. Age ≥ 18 years
4. Receiving or willing to receive supplemental iron therapy (unless contraindicated)
5. Receiving or willing to receive erythropoiesis-stimulating agent (EPO) therapy
6. Patient or legally authorized representative provided consent to participate
7. Investigator determination that the patient is an appropriate candidate for study enrollment

Exclusion Criteria:

1. Hemoglobin ≤ 2 g/dL
2. Presence of severe trauma (e.g., Injury Severity Score (ISS)/New Injury Severity Score (NISS) Score ≥ 25)
3. Unable to provide sufficient blood sample volume for screening assessments; or
4. Pregnant; or
5. Investigator determination that the patient is not an appropriate candidate for study enrollment