Erythropoietin monitoring

Decreased red blood cell (RBC) count, hemoglobin (Hgb) and hematocrit (Hct) iron metabolism may also be altered [iron level, total iron binding capacity (TIBC), serum ferritin level, and transferrin saturation (TSAT)]. Erythropoietin levels are not routinely monitored and are generally normal to low. Urine positive for albumin or protein. 

The response to erythropoietin products must be monitored closely to prevent adverse effects associated with these agents. The common adverse effects experienced include hypertension and thrombosis. Concomitant drugs with the same adverse-effect profile may increase a patient s risk for these complications. Also, the patient s overall survival may be decreased if the hemoglobin level is titrated to above the recommended 11 to 12 g/dL (110-120 g/L or 6.82-7.44 mmol/L) value. Therefore, it is important to follow the dosing and titration scheme recommended by the NCCN and summarized in... 

Although EPO deficiency is the primary cause of CKD anemia, iron deficiency is often present, and it is essential to assess and monitor the CKD patient s iron status (NKF-K/DOQI guidelines). Iron stores in patients with CKD should be maintained so that transferrin saturation (TSAT) is greater than 20% and serum ferritin is greater than 100 ng/mL (100 mcg/L or 225 pmol/L). If iron stores are not maintained appropriately, epoetin or darbepoetin will not be effective, and most CKD patients will require iron supplementation. Oral iron therapy can be used, but it is often ineffective, particularly in CKD patients on dialysis. Therefore, intravenous iron therapy is used extensively in these patients. Details of the pharmacology, pharmacokinetics, adverse effects, interactions, dose, and administration of erythropoietin and iron products have been discussed previously. 

Erythropoietin products hypertension (monitor blood pressure), thrombosis (e.g., DVT/PE, Ml, CVA, and TIA), arthralgias, and headache... 

Bone marrow suppression ZDV Onset Few weeks to months Symptoms Fatigue, risk of T bacterial infections due to neutropenia anemia, neutropenia 1. Advanced HIV 2. High dose ZDV 3. Preexisting anemia or neutropenia 4. Concomitant use of bone marrow suppressants Avoid in patients with high risk for bone marrow suppression avoid other suppressing agents monitor CBC with differential at least every 3 months Switch to another NRTI D/C concomitant bone marrow suppressant, if possible for anemia Identify and treat other causes consider erythropoietin treatment or blood transfusion, if indicated for neutropenia Identify and treat other causes consider filgrastim treatment, if indicated... 

Cancer patients on chemotherapy Treatment of patients with grossly elevated serum erythropoietin levels (eg, greater than 200 milliunits/mL) is not recommended. Monitor hemoglobin on a weekly basis in patients receiving epoetin alfa therapy until... 

Epoetin Alfa [Erythropoietin/ EPO] (Epogen/ Procrit) [Recombinant Human Erythropoietin] WARNING Use lowest dose possible may be associated w/1 CV, thromboembolic events /or mortality D/C if Hgb >12 g/dL Uses CRF associated anemia zidovudine Rx in HIV-infected pts, CA chemo -1- transfusions associated w/ surgery Action Induces ery-thropoiesis Dose Adul Peds. 50-150 Units/kg IV/SQ 3x/wk adjust dose q4-6wk PRN Surgery 300 Units/kg/d x 10 d before to 4 d after -I dose if Hct 36% or Hgb, T > 12 g/dL or Hgb t >1 g/dL in 2-wk pmod hold dose if Hgb >12 g/dL Caution [C, +] Contra Uncontrolled HTN Disp Inj SE HTN, HA, fatigue, fever, tach, NA Interactions None noted EMS Monitor ECG for hypokalemia (peaked T waves) t risk of CV thrombotic events OD May cause HA, dizziness, SOB and polycythemia symptomatic and supportive... 

The most common adverse effects of erythropoietin are associated with a rapid increase in hematocrit and hemoglobin and include hypertension and thrombotic complications. These difficulties can be minimized by raising the hematocrit and hemoglobin slowly and by adequately monitoring and treating hypertension. Allergic reactions have been infrequent and mild. 

Antibodies specific for a hormone erythropoietin, are being tested as a monitor for hormone therapy of anemia. The antibody can be used to identify the misuse of the hormone by athletes to enhance performance in competitive sports. 

ACE INHIBITORS AZATHIOPRINE Risk of anaemia with captopril and enalapril and leukopenia with captopril The exact mechanism is uncertain. Azathioprine-induced impairment of haematopoiesis and ACE inhibitor-induced l in erythropoietin may cause additive effects. Enalapril has been used to treat post-renal transplant erythrocytosis Monitor blood counts regularly... 

ANGIOTENSIN II RECEPTOR ANTAGONISTS EPOETIN 1 efficacy of angiotensin II receptor antagonists and possible t risk of hyperkalaemia Angiotensin II is believed to sustain the secretion of erythropoietin and to stimulate the bone marrow to produce erythrocytes. Epoetin has a direct contractile effects on vessels Monitor BP at least weekly until stable. Monitor serum potassium every week until stable, then every 3-6 months... 

When used in patients without iron overload, deferoxamine can cause iron deficiency (12). In 20 patients, there were falls in ferritin concentrations in six, requiring withdrawal of deferoxamine and parenteral administration of iron dextran (12). Monitoring ferritin concentrations is therefore recommended in patients receiving deferoxamine for aluminium overload. On the other hand, the administration of deferoxamine (500mg/day by subcutaneous infusion) improves chronic anemia in patients with rheumatoid arthritis (77). This effect is thought to be achieved through increased erythropoietin responsiveness, secondary to iron chelation. Iron chelation with deferoxamine also improves hemopoiesis in patients with myelodysplastic syndromes and can reduce transfusion dependency (78). Exactly how deferoxamine works in these patients remains to be explained. 

ACE INHIBITORS EPOETIN -L haematopoietic effects of epoetin, i efficacy of ACE inhibitors Angiotensin II is believed to be responsible for sustaining secretion of erythropoietin and for stimulating the bone marrow to produce erythrocytes. Epoetin has direct contractile effects on vessels (causing t BP) Watch for poor response to erythropoietin and to ACE inhibitors. These effects may be delayed so monitor for the duration of co-administration... 

The authors of the first study suggested that this haemolytic uraemic syndrome was due to a combination of subclinical endothelial damage induced by mitomycin C, and a thrombotic effect on platelets caused by tamoxifen. They advise the avoidance of tamoxifen with or shortly after mitomycin C unless concurrent use ean be earefully monitored. Erythropoietin may be useful in managing the syndrome. This syndrome has also occurred rarely with mitomycin alone, or when combined with fluorouracil, see Mitomycin + Fluorouracil , above. 

Myelosuppression is dose dependent monitoring white blood counts is usually sufficient for detecting bone marrow suppression. The nadir white blood cell count is usually encountered 9 days after an IV dose, but the range can be 6 to 21 days (215). Monocytosis is an early indicator of bone marrow recovery from chemotherapy, while low monocyte counts portend prolonged leukopenia (216). Anemia is a consequence of chronic CP use. Patients with hemoglobin levels of less than 11 gm% should be considered for erythropoietin therapy (217). 

Segura, J., Pascual, J.A., and Gutierrez-Gallego, R. (2007) Procedures for monitoring recombinant erythropoietin and analogues in doping control. Analytical and Bioanalytical Chemistry. 388,1521-1529. 

Pascual, J., Belalcazar, V., de Bolos, C., et al. (2004) Recombinant erythropoietin and analogues A challenge for doping control. Therapeutic Drug Monitoring, 26,175-179. 

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