What is the best approach to treating anemia in a critically ill patient?

Treatment of Anemia of Critical Illness

The mainstay of treatment for anemia in critically ill patients is restrictive red blood cell transfusion using a hemoglobin threshold of <70 g/L (7 g/dL) for most patients, combined with phlebotomy reduction strategies, while avoiding routine iron therapy and erythropoietin except in specific circumstances. 1

Transfusion Strategy

Restrictive Transfusion Threshold

• Transfuse at hemoglobin <70 g/L (7 g/dL) for most critically ill patients, including those with ARDS and septic shock. 1
• This restrictive approach reduces mortality and morbidity compared to liberal transfusion strategies. 1
• The optimal threshold remains uncertain for patients with acute coronary syndromes or ischemic heart disease—consider a higher threshold of <80 g/L (8 g/dL) in these populations. 1

Single-Unit Transfusion Policy

• Transfuse one unit of packed red blood cells at a time, then reassess hemoglobin before deciding on additional units. 1
• Each unit increases hemoglobin by approximately 1 g/dL. 2
• Avoid standing orders for multiple units, as this increases unnecessary transfusion exposure. 1

Blood Product Selection

• Use red blood cells regardless of storage time—there is no evidence that fresher blood improves outcomes. 1
• Leuko-depleted blood is preferred when available, as it may reduce transfusion-related complications. 1

Prevention of Iatrogenic Anemia

Phlebotomy Reduction Strategies

• Implement small-volume blood collection tubes to minimize diagnostic blood loss. 1
• A large cluster RCT demonstrated that small-volume tubes decrease RBC transfusions without affecting laboratory analysis. 1
• Avoid standing orders for routine blood draws—order only necessary tests. 1
• Use blood conservation devices on extracorporeal circuits when applicable. 1

Hemoglobin Monitoring

• Monitor hemoglobin weekly after initiating or adjusting therapy until stable, then at least monthly. 1
• Hemoglobin drops by a mean of 0.52 g/L per day in ICU patients. 1

Non-Transfusion Pharmacologic Therapy

Erythropoietin

• Consider erythropoietin treatment specifically in trauma patients without contraindications. 1
• Available evidence does NOT support routine use of erythropoietin in general critically ill populations—improvements in hemoglobin have not translated into reduced blood usage or improved clinical outcomes. 1
• The FDA warns that erythropoietin increases risks of death, myocardial infarction, stroke, and thromboembolism when targeting hemoglobin >11 g/dL. 3
• Erythropoietin is NOT indicated as a substitute for RBC transfusions in patients requiring immediate correction of anemia. 3

Iron Therapy

• Avoid routine iron therapy in critically ill patients except when administered concurrently with erythropoietin. 1
• Evaluate iron status before and during treatment—administer supplemental iron when ferritin <100 mcg/L or transferrin saturation <20% only if using erythropoietin. 1
• The majority of CKD patients will require supplemental iron during ESA therapy. 3

Understanding Anemia of Critical Illness

Pathophysiology

• Anemia of critical illness is characterized by disturbed iron homeostasis, impaired erythropoiesis, reduced red cell survival, and blunted erythropoietin production. 1
• This is identical to anemia of chronic disease, driven by inflammatory cytokines (TNF, IL-1, IL-6) and increased hepcidin. 1
• Contributing factors include haemodilution, phlebotomy blood loss, extracorporeal circuits, and surgery. 1

Prevalence and Natural History

• Approximately 30-40% of critically ill patients develop moderately severe anemia (Hb <90 g/L) during their ICU stay. 1
• More than half of patients anemic at ICU discharge remain anemic 6 months later. 1

Critical Pitfalls to Avoid

Transfusion-Related Risks

• Recognize that RBC transfusion carries substantial risks including increased infection, multi-organ failure, transfusion-related acute lung injury (TRALI), and transfusion-associated circulatory overload (TACO). 1
• Blood transfusions are associated with transfusion-associated immunomodulation (TRIM) and leukocyte microchimerism. 1
• Human error in blood component administration remains a significant risk. 1

Avoid Targeting Normal Hemoglobin

• Never target hemoglobin levels >11 g/dL—this increases mortality, stroke, myocardial infarction, and thromboembolism without improving outcomes. 1, 3
• No trial has identified a hemoglobin target, ESA dose, or dosing strategy that eliminates these risks. 3

Do Not Delay Necessary Transfusion

• In patients with hemoglobin <70 g/L with respiratory symptoms or hemodynamic instability, transfusion should not be delayed while awaiting diagnostic results—this represents a life-threatening emergency. 2, 4

Avoid Frequent Dose Adjustments

• If using erythropoietin, do not increase the dose more frequently than once every 4 weeks—avoid frequent dose adjustments. 3
• If hemoglobin rises rapidly (>1 g/dL in 2 weeks), reduce the erythropoietin dose by 25% or more. 3

Special Populations

Patients with Malignancy

• Patients with solid organ and hematological malignancy often require blood components, but there is no agreed consensus on optimal transfusion threshold. 1
• Evidence in these groups is largely from single-center RCTs. 1

Hemorrhage Control

• In active hemorrhage, do not attempt to normalize blood pressure—achieve a lower acceptable blood pressure with volume resuscitation alone. 1
• This may need modification in traumatic brain injury where brain injury is the dominant condition. 1
• Implement major hemorrhage protocols for volume resuscitation during uncontrolled hemorrhage. 1