From the Guidelines
A major complication of using erythropoietin stimulating agents (ESAs), especially when hemoglobin levels exceed 12 g/dL, is an increased risk of thromboembolic events, including stroke, myocardial infarction, deep vein thrombosis, pulmonary embolism, and vascular access thrombosis, as reported by Tonelli et al. 1 and Glaspy et al. 1. These complications can be life-threatening and have a significant impact on morbidity, mortality, and quality of life.
- The risk of thromboembolic events is particularly concerning in patients with pre-existing cardiovascular disease or those on dialysis.
- ESA therapy with elevated hemoglobin targets has been associated with increased mortality in chronic kidney disease patients, as noted in the study by Glaspy et al. 1.
- Other potential complications include hypertension, which may worsen with ESA therapy, and in rare cases, pure red cell aplasia. Key considerations for safe ESA management include:
- Maintaining hemoglobin levels between 10-11 g/dL in patients receiving ESAs.
- Dose reductions are recommended when hemoglobin approaches or exceeds 12 g/dL, as outlined in the guidelines by the American Society of Hematology/American Society of Clinical Oncology 1.
- Regular monitoring of hemoglobin levels (every 1-4 weeks during initiation and dose adjustments) is essential for safe ESA management, as emphasized in the study by Bohlius et al. 1. The FDA label now limits the indication for ESA use to patients receiving chemotherapy for palliative intent, and the use of ESAs in patients with cancer should be carefully weighed against the risks of thromboembolism, as stated in the guidelines by the American Society of Clinical Oncology/American Society of Hematology 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Major Complications of Erythropoietin Stimulating Agents
- A major complication of using erythropoietin stimulating agents, especially when hemoglobin is greater than 12, is the increased risk of thrombotic events, including venous thromboembolism and arterial thrombotic events 2, 3, 4.
- The use of erythropoietin stimulating agents has been associated with a higher cardiovascular event and mortality rate in dialysis patients, particularly when targeting high hemoglobin levels 2, 5, 6.
- Elevated blood viscosity appears to be a key determinant of the work of the heart and an important pathophysiological factor in the development of atherothrombosis, which may contribute to the increased risk of cardiovascular events 3.
- The risk of thrombotic complications is multifaceted and context dependent, and may require the presence of additional prothrombotic factors, such as polycythemia/hyperviscosity syndrome, hypertension, thrombocytosis, platelet hyperactivity, and activation of blood coagulation 4.
Hemoglobin Levels and Erythropoietin Stimulating Agents
- Targeting higher hemoglobin levels with erythropoietin stimulating agents has been associated with an increased risk of adverse vascular outcomes, including cardiovascular complications and mortality 5, 6.
- The optimal target hemoglobin range for erythropoietin stimulating agent therapy is still debated, but current recommendations suggest aiming for a hemoglobin level between 9.5-12.5 g/dL 5, 6.
- Using the lowest effective erythropoietin stimulating agent dose and better managing the problem of erythropoietin stimulating agent hyporesponsiveness may help minimize the risk of thrombotic complications and other adverse events 6.