Benefits and risks of erythrocyte-stimulating agents

Table 1 Risks associated with blood transfusions[1]

Adverse effects
Fever/allergic reactions
Hemolytic reaction
TRALI
Anaphylaxis
Fatal hemolysis
GVHD
Thrombotic complications
Mistransfusion

TRALI: Transfusion-related acute lung injury; GVHD: Graft-versus-host disease.

Table 2 Erythrocyte-stimulating agents hyposensitivy (Kidney Disease Improving Global Outcomes Guideline 2012)[20]

Initial ESA hyporesponsiveness

Classify patients as having ESA hyporesponsiveness if they have no increase in Hb concentration from baseline after the first month of ESA treatment on appropriate weight-based dosing

In patients with ESA hyporesponsiveness, avoid repeated escalations of the ESA dose beyond double the initial weight-based dose

Subsequent ESA hyporesponsiveness

Classify patients as having acquired ESA hyporesponsiveness if after treatment with stable doses of ESA, they require two increases in ESA doses up to 50% beyond the dose at which they had been stable in an effort to maintain a stable Hb concentration

In patients with acquired ESA hyporesponsiveness, avoid repeated escalations in ESA dose beyond double the dose at which they had been stable

Management of poor ESA responsiveness

Evaluate patients with either initial or acquired ESA hyporesponsiveness and treat for specific causes of poor ESA response

For patients who remain hyporesponsive despite the correction of treatable causes, accounting for relative risks and benefits: decline in Hb concentration; continuing ESA if needed to maintain Hb concentration, with due consideration of the doses required; blood transfusions

ESA: Erythrocyte-stimulating agent; Hb: Hemoglobin.

Table 3 Practical approach in the presence of erythrocyte-stimulating agents resintance (Kidney Disease Improving Global Outcomes Guideline 2012)[20]

Tests	Finding and action
Check adherence	If poor, attempt to improve (if self-injection)
Reticulocyte count	If > 130000/μL, look for blood loss or hemolysis: endoscopy, colonoscopy, hemolysis screen
Serum vitamin B12, folate	If low, replenish
Iron status	If low, replenish iron
Serum PTH	If elevated, manage hyperparathyroidism
Serum CRP	If elevated, check for and treat infection or inflammation
Underdialysis	If underdialyzed, improve dialysis efficiency
ACEi/ARB use	If yes, consider reducing dose or discontinuing drug
Bone marrow biopsy	Manage condition diagnosed, e.g., dyscrasia, infiltration, fibrosis

ACEi: Angiotensin-converting enzyme inhibitor; ARB: Angiotensin-receptor blocker; CRP: C-reactive protein; PTH: Parathyroid hormone.

Table 4 Nonhematologic complications associated with erythropoietin therapy[11]

Adverse effects
Hypertension
Injection site pain
Seizure
Pure red cell aplasia
Liver dysfunction
Shock, anaphylaxis
Thrombotic complications

Table 5 Evaluation for pure red cell aplasia (Kidney Disease Improving Global Outcomes Guideline 2012)[20]

Investigate for possible antibody-mediated PRCA when a patient receiving ESA therapy for more than 8 wk develops the following:

Sudden rapid decrease in Hb concentration at the rate of 0.5 to 1.0 g/dL (5 to 10 g/L) per week OR requirement of transfusions at the rate of approximately 1 to 2 per week

Normal platelet and white cell counts

Absolute reticulocyte count less than 10000/mL

ESA therapy should be stopped in patients who develop antibody-mediated PRCA

Peginesatide should be used to treat patients with antibody-mediated PRCA

PRCA: Pure red cell aplasia; ESA: Erythrocyte-stimulating agents; Hb: Hemoglobin.