Majority of the reported complications associated with erythropoietin therapy are not due to the recombinant product but due to the resultant increase in hematocrit and blood viscosity.
- Hypertension is the most common adverse effect associated with erythropoietin therapy, occurring in approximately 20–30% of patients treated. Most of the hypertensive problems occur during the acute correction of anemia rather than during the maintenance phase. Hypertension due to erythropoietin appears to be peculiar to renal patients, and very rare in non-renal patients receiving erythropoietin therapy. Erythropoietin-induced hypertension may be due to an inadequate reversal of the elevated cardiac output of anemia, increase in blood viscosity, increased endothelin production, reduced nitric oxide production, and possibly a direct pressor effect of erythropoietin. Hypertension is easily controlled by fluid removal and the use of standard antihypertensive drugs; it is very rare to have to stop erythropoietin for severe uncontrollable hypertension
- Seizures or hypertensive encephalopathy is seen in patients receiving erythropoietin, usually within the first 3 months of treatment, may be due to loss of autoregulation of cerebral blood flow and/or reduced cerebral perfusion.
- Vascular access thrombosis and clotting of dialysis lines are seen in 10% of hemodialysis patients receiving erythropoietin therapy. Commonly seen in prosthetic graft patients than with native fistula, possibly due to increase in blood viscosity,shortening of the bleeding time, enhanced platelet aggregation and adhesion, a reduction in protein C and protein S levels, an increase in thrombin-antithrombin III levels, enhanced Factor VIII-related activities, and a marginal increase in platelet count in some patients.
- Hyperkalemia, an increase in serum potassium, phosphate, and creatinine may be due to enhanced dietary intake and/or reduced dialyzer clearance of these molecules secondary to the increased hematocrit.
- Myalgia or influenza-like symptoms only seen in the first few injections.
- Pure Red Cell Aplasia(PRCA), caused by the formation of antibodies to erythropoietin. Very rare, thought to be due to change in immunogenicity of the erythropoietin molecule brought by removing human albumin from the solvent.
- Skin irritation around the injection site caused by citrate buffer seen in the subcutaneous infusion of erythropoietin.
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