• Change in self-reported fatigue level [ Time Frame: Fatigue will be measured at admission to the hospital during the index hospitalization and 7 days after hospital discharge. ]
  Self-reported fatigue will be measured by the Patient-Reported Outcome Measurement Information System (PROMIS-F) Fatigue 8a instrument.The PROMIS-F scores range from 8-40, with higher scores indicating greater fatigue.
• Change in self-reported activity level [ Time Frame: Activity will be measured at admission to the hospital during the index hospitalization and 7 days after hospital discharge. ]
  Self-reported activity will be measure by the Physical Activity Scale for the Elderly (PASE). Higher scores on the PASE indicated greater physical activity.
• Change in 6 Minute Walk Test (6MWT) distance [ Time Frame: 6MWT will be measured at admission to the hospital during the index hospitalization and 7 days after hospital discharge. ]
  6MWT is measure of functional capacity

The design of this proposed study is a randomized controlled trial of hospitalized adult general medicine patients with anemia at the University of Chicago (UC). Patients will be randomized to receive transfusion at either a hemoglobin (Hb)<9g/dL (liberal arm) or a Hb<7g/dL (restrictive arm) throughout their hospitalization. Self-reported fatigability, fatigue, and activity levels will be measured in consented patients at randomization and through a follow-up phone call 7 days after hospital discharge. We will also enroll 150 patients to participate in the Six Minute Walk Test85,86 (6MWT) at randomization and in the clinic 7 days after hospital discharge.

This trial will test whether a liberal transfusion strategy is superior to a restrictive transfusion in hospitalized patients with anemia on fatigability levels after hospital discharge. Our primary outcome is self-reported fatigability level 7 days after hospital discharge measured using the Pittsburgh Fatigability Scale (PFS)71. Secondary outcomes include fatigue measured using the Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Aa instrument, and activity measured by the Physical Activity Scale for the Elderly, and 6MWT distance.

Eligible patients for this trial will be recruited from the University of Chicago Medical Center (UCMC) general medicine services using the University of Chicago Hospitalist Project (UCHP) research infrastructure. The eligibility criteria is: 1) hospitalized adult >18 years of age, 2) admitted to the general medicine services at the University of Chicago, 3) any Hb concentration of <9g/dL during their hospitalization. We will exclude patients who: 1) decline blood transfusion, 2) and/or who have a diagnosis of sickle cell anemia, 3) and/or are brain dead or receiving only palliative treatment, 4) and/or are unable to follow-up after discharge. We will not exclude patients who received transfusion prior to randomization. Eligible patients will be identified using the encrypted UCHP research database, which is programmed to extract real time EHR data into the database in order to identify patients potentially eligible for participation in research studies. The PI and Study Coordinator (SC) will be responsible for patient recruitment and consent.

Consenting patients will be randomized to either receive transfusion when their Hb drops below 7g/dL (restrictive arm) or 9g/dl (liberal arm) at any point during hospitalization, and randomized assignment will be done using permuted block design with random blocks of 2, 4, or 6 patients per block. All red blood cell (RBC) transfusions will be administered in 1 unit increments in order to maintain patients' Hb concentration above the trial arm threshold they are randomized to. All transfusions will be followed by a Hb measure and an additional unit(s) of RBC's will only be transfused if there is documentation of the patient's Hb concentration below the trial arm threshold they are randomized to. However, In the case of life-threatening bleeding clinicians will be free to transfuse patients without first checking a patient's Hb concentration. Once randomized, patient's will be managed according to protocol until hospital discharge independent of transfusion to another service and/or specialized hospital ward. This trial will not control or dictate transfusion of other blood products, which will be administered at the discretion of the attending physician caring for the patient.

• Anemia
• Red Blood Cell Transfusion
• Fatigability
• Fatigue
• Physical Function

• Active Comparator: Liberal Transfusion Arm
  Patient's in the liberal transfusion arm will receive a 1 unit RBC transfusion following randomization and will re-ceive blood in additional 1 unit increments until their Hb is above 9g/dL. At any point during the patient's hospital-ization if their Hb subsequently falls below 9g/dL, they will again be transfused to maintain a Hb>9g/dL, and this will be maintained throughout their hospitalization.
  Intervention: Other: Red blood cell transfusion
• Active Comparator: Restrictive Transfusion Arm
  Patients in the restrictive transfusion arm will receive transfusion if their Hb concentration falls below 7g/dL. RBC's will be administered 1 unit at a time and enough blood will be given to increase patient's Hb to above 7g/dL.
  Intervention: Other: Red blood cell transfusion

Inclusion Criteria:

• Age ≥ 18 years
• Hospitalized on a general medicine service at the University of Chicago
• Any hemoglobin (Hb) concentration <9g/dL

Exclusion Criteria:

• Have sickle cell anemia
• Decline blood transfusion
• Are receiving palliative care treatment only
• Are brain dead
• Cannot follow up after hospital discharge