Erythropoietin (EPO) is a naturally occurring hormone produced primarily by the kidneys. It stimulates the bone marrow to produce red blood cells, which carry oxygen throughout the body. A synthetic version, such as epoetin alfa, is widely used to treat anemia linked to chronic kidney disease, chemotherapy, or certain HIV treatments. Like all medications, EPO can have side effects.
Frequent Side Effects
Patients undergoing EPO therapy may experience several common effects. These include itching or stinging at the injection site and flu-like symptoms such as fever, chills, and muscle and joint aches. These symptoms, along with general tiredness, dizziness, and headaches, are often more noticeable when treatment first begins.
Another common effect is an increase in blood pressure; about one-third of patients may experience a rise or require adjustments to their existing antihypertensive medications. Other common effects include nausea, vomiting, constipation, and bone pain.
Severe Side Effects
Despite its benefits, EPO therapy carries the possibility of serious, though less common, effects. Cardiovascular events are a significant concern, including an increased risk of blood clots, stroke, heart attack, and congestive heart failure. Blood clots can develop in the legs (deep vein thrombosis), travel to the lungs (pulmonary embolism), or form at vascular access sites in dialysis patients.
The risk of stroke is also elevated with EPO use, particularly when higher target hemoglobin levels are pursued or in patients with certain cancers. This increased risk may be linked to changes in blood viscosity or the dosage of the medication.
For individuals with cancer, EPO therapy has been associated with a shortened survival time and a worsening of tumor progression in specific types of cancer, including those affecting the breast, head, neck, and lung. This effect may occur because some cancer cells possess EPO receptors, potentially stimulating tumor growth, invasion, or protecting them from chemotherapy and radiation.
A rare but severe effect is pure red cell aplasia (PRCA), where the bone marrow abruptly stops producing red blood cells. This happens when the body develops antibodies against the synthetic EPO, which then also neutralize the body’s natural erythropoietin. PRCA results in severe anemia, a very low count of immature red blood cells (reticulocytes), and often requires regular blood transfusions. Most reported instances of PRCA have occurred in patients with chronic kidney disease who received EPO subcutaneously.
Factors Increasing Risk
Certain patient characteristics and treatment approaches can increase the likelihood of experiencing EPO’s effects. Patients with existing cardiovascular conditions, such as a history of heart disease, stroke, or previous blood clots, face a higher risk of adverse cardiovascular events when on EPO therapy.
Uncontrolled high blood pressure is another important factor, as EPO treatment can further elevate blood pressure or complicate its management. For this reason, EPO is generally not recommended for individuals whose hypertension is not adequately controlled. Additionally, the type of cancer a patient has can influence risk, with specific cancers like those of the breast, head and neck, and lung showing increased concerns regarding tumor progression.
The dosage of EPO and the target hemoglobin levels also play a role in determining risk. Administering higher doses of EPO or aiming for hemoglobin levels above a certain threshold, such as 11-12 g/dL, has been associated with an increased risk of cardiovascular complications and even mortality. For patient safety, healthcare providers typically aim to use the lowest effective dose of EPO to achieve the desired hemoglobin level without increasing risks. The duration of treatment can also be a consideration, as prolonged exposure might influence overall risk profiles.
What to Watch For and When to Get Help
Patients on EPO therapy should know what signs to observe and when to seek medical attention. Any indication of a blood clot, such as pain, redness, or swelling in an arm or leg, or a limb feeling cool or appearing pale, should be reported immediately. Chest pain or sudden difficulty breathing also warrant urgent medical evaluation, as these could signal a clot in the lungs. For dialysis patients, unexpected clotting at the access port needs prompt attention.
Symptoms suggestive of a stroke, including sudden numbness or weakness on one side of the body, a severe headache that appears suddenly, slurred speech, or problems with vision or balance, require emergency medical care. Similarly, signs of a heart attack, such as chest pain or pressure that spreads to the jaw or shoulder, nausea, or sweating, should prompt immediate medical help. Severe headaches, blurred vision, a pounding sensation in the neck or ears, or anxiety could indicate dangerously high blood pressure.
Any signs of a serious allergic reaction, such as hives, itching, swelling of the face, throat, or tongue, or difficulty breathing, also necessitate emergency medical attention. Patients should also be aware of severe skin reactions, including blistering, peeling skin, or the development of red skin lesions.
Regular monitoring by healthcare providers, including blood pressure checks and blood tests to assess hemoglobin and iron levels, is a routine part of EPO therapy. Open communication with the healthcare team about any new or worsening symptoms is important for safe and effective management.