Possible complications of erythropoietin therapy in patients with chronic renal failure

There have been many publications in the past 20 years about positive effects of human recombinant erythropoietin, which is used in treatment of anemia, especially in patients on dialysis. The most important complications in patients treated with erythropoietin include: hypertensive reactions; throm...

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Published inMedicinski pregled Vol. 57; no. 5-6; pp. 254 - 257
Main Author Pljesa, Steva
Format Journal Article
LanguageSerbian
English
Published Serbia 01.05.2004
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Abstract There have been many publications in the past 20 years about positive effects of human recombinant erythropoietin, which is used in treatment of anemia, especially in patients on dialysis. The most important complications in patients treated with erythropoietin include: hypertensive reactions; thrombosis of AV fistula in patients on hemodialysis and appearance of severe anemia as a part of Pure Red Cell Aplasia (PRCA). The first two complications were managed quite easily with adequate erythropoietin dosage, and slower establishment of normal hemoglobin kevel, hematocrit level and red blood cell count, (our "target" Hb varied between 100 and 110 g/dl). PURE RED CELL APLASIA (PRCA): Pure Red Cell Aplasia is a progressive, marked anemia with sudden appearance of significant loss or complete absence of erythrocyte precursor cells in normal bone marrow. In patients with end stage renal disease treated with erythropoietin PRCA appears in acute form as a consequence of production of neutralizing antibodies to erythropoietin. Time period between the beginning of erythropoietin therapy and appearance of PRCA is from 3 weeks to approximately 9 months. PRCA is characterized by sudden appearance of anemia in patients who had a satisfactory response to erythropoietin therapy till that moment. In PRCA, anemia is normocytic, normochromic with normal survival of red blood cells, without deficit in components such as iron, folic acid or vitamin B12, low reticulocyte count, decrease in Hg and normal platelet count. Diagnosis is based on clinical data (marked anemia), bone marrow biopsy, which shows a lower number of precursor red blood cells and presence of antibodies against erythropoietin. Before PRCA is diagnosed, all other causes for erythropoietin resistance must be excluded. Therapy of PRCA is based on cessation of erythropoietin therapy (all kinds), and correction of anemia with blood transfusions. PRCA is very rare and occurs in less than 1:10.000 patient-years in patients treated with erythropoietin, not lethal by itself and generally reversible. Till December 31, 2002. PRCA has been diagnosed in 142 patients world wide. In Serbia and Montenegro till this moment there hasn't been a single case of this syndrome. Continuous follow-up of reticulocyte count is the first step. Although this is a very rare disease, most of European Societies of Nephrology made protocols that recommend only intravenous application of -epoetin. Considering this new situation, Nephrology Society of Serbia and Montenegro recommends that -epoetin should be given to patients on hemodialysis only intravenously, while subcutaneous application of -epoetin is recommended in patients before beginning the dialysis treatment and in patients on hemodialysis, or who had undergone kidney transplantation.
AbstractList Introduction There have been many publications in the past 20 years about positive effects of human recombinant erythropoietin, which is used in treatment of anemia, especially in patients on dialysis. Complications The most important complications in patients treated with erythropoietin include: hypertensive reactions; thrombosis of AV fistula in patients on hemodialysis and appearance of severe anemia as a part of Pure Red Cell Aplasia (PRCA). The first two complications were managed quite easily with adequate erythropoietin dosage, and slower establishment of normal hemoglobin kevel, hematocrit level and red blood cell count, (our "target" Hb varied between 100 and 110 g/dl). Pure Red Cell Aplasia (PRCA) Pure Red Cell Aplasia is a progressive, marked anemia with sudden appearance of signifacnt loss or complete absence of erythrocyte precursor cells in normal bone marrow. In patients with end stage renal disease treated with erythropoietin PRCA appears in acute form as a consequence of production of neutralizing antibodies to erythropoietin. Time period between the beginning of erythropoietin therapy and appearance of PRCA is from 3 weeks to approximately 9 months. Symptoms and signs PRCA is characterized by sudden appearance of anemia in patients who had a satisfactory response to erythropoietin therapy till that moment. In PRCA, anemia is normocytic, normochromic with normal survival of red blood cells, without deficit in components such as iron, folic acid or vitamin B12, low reticulocyte count, decrease in Hg and normal platelet count. Diagnosis Diagnosis is based on clinical data (marked anemia), bone marrow biopsy, which shows a lower number of precursor red blood cells and presence of antibodies against erythropoietin. Before PRCA is diagnosed, all other causes for erythropoietin resistance must be excluded. Therapy Therapy of PRCA is based on cessation of erythropoietin therapy (all kinds), and correction of anemia with blood transfusions. Incidence PRCA is very rare and occurs in less than 1:10.000 patient-years in patients treated with erythropoietin, not lethal by itself and generally reversible. Till December 31, 2002. PRCA has been diagnosed in 142 patients world wide. In Serbia and Montenegro till this moment there hasn't been a single case of this syndrome. Preventive measures Continuous follow-up of reticulocyte count is the first step. Although this is a very rare disease, most of European Societies of Nephrology made protocols that recommend only intravenous application of -epoetin. Considering this new situation, Nephrology Society of Serbia and Montenegro recommends that -epoetin should be given to patients on hemodialysis only intravenously, while subcutaneous application of -epoetin is recommended in patients before beginning the dialysis treatment and in patients on hemodialysis, or who had undergone kidney transplantation. O pozitivnim efektima eritropoetina postoje brojni radovi objavljeni u poslednjih dvadesetak godina, koliko se koristi u lecenju anemije, posebno kod bolesnika na dijalizi. U nasoj zemlji primena rekombinovanog humanog eritropoetina zapocela je vec krajem osamdesetih godina i veoma brzo smo stekli licna iskustva u primeni ovog leka. Kao najznacajnije komplikacije, kod bolesnika koji su primali rekombinovani humani eritropoetin, navode se hipertenzivne reakcije, tromboza fistula kod bolesnika na hemodijalizi, te pojava ozbiljnih anemija u sklopu Pure Red Cell Aplasia. Radi se o progresivnoj, izrazenoj, anemiji sa iznenadnim pojavljivanjem znacajnog smanjenja ili potpunog odsustva celija prekurzora eritrocitne loze iz inace normalne kostne srzi. Kod bolesnika sa terminalnom bubreznom insuficijencijom ova bolest se javlja u akutnom obliku, kao posledica stvaranja neutralisucih antitela na eritropoetin kod bolesnika koji su se nalazili na terapiji rekombinovanim humanim eritropoetinom. Vremenski interval izmedju zapocinjanja eritropoetinske terapije i pojave PRCA sindroma je prosecno od 3 nedelje do 9 meseci, dijagnosticki je najvazniji pad broja retikulocita a terapija ovog sindroma sastoji se u prekidu davanja eritropoetina i lecenju anemije transfuzijama.
There have been many publications in the past 20 years about positive effects of human recombinant erythropoietin, which is used in treatment of anemia, especially in patients on dialysis. The most important complications in patients treated with erythropoietin include: hypertensive reactions; thrombosis of AV fistula in patients on hemodialysis and appearance of severe anemia as a part of Pure Red Cell Aplasia (PRCA). The first two complications were managed quite easily with adequate erythropoietin dosage, and slower establishment of normal hemoglobin kevel, hematocrit level and red blood cell count, (our "target" Hb varied between 100 and 110 g/dl). PURE RED CELL APLASIA (PRCA): Pure Red Cell Aplasia is a progressive, marked anemia with sudden appearance of significant loss or complete absence of erythrocyte precursor cells in normal bone marrow. In patients with end stage renal disease treated with erythropoietin PRCA appears in acute form as a consequence of production of neutralizing antibodies to erythropoietin. Time period between the beginning of erythropoietin therapy and appearance of PRCA is from 3 weeks to approximately 9 months. PRCA is characterized by sudden appearance of anemia in patients who had a satisfactory response to erythropoietin therapy till that moment. In PRCA, anemia is normocytic, normochromic with normal survival of red blood cells, without deficit in components such as iron, folic acid or vitamin B12, low reticulocyte count, decrease in Hg and normal platelet count. Diagnosis is based on clinical data (marked anemia), bone marrow biopsy, which shows a lower number of precursor red blood cells and presence of antibodies against erythropoietin. Before PRCA is diagnosed, all other causes for erythropoietin resistance must be excluded. Therapy of PRCA is based on cessation of erythropoietin therapy (all kinds), and correction of anemia with blood transfusions. PRCA is very rare and occurs in less than 1:10.000 patient-years in patients treated with erythropoietin, not lethal by itself and generally reversible. Till December 31, 2002. PRCA has been diagnosed in 142 patients world wide. In Serbia and Montenegro till this moment there hasn't been a single case of this syndrome. Continuous follow-up of reticulocyte count is the first step. Although this is a very rare disease, most of European Societies of Nephrology made protocols that recommend only intravenous application of -epoetin. Considering this new situation, Nephrology Society of Serbia and Montenegro recommends that -epoetin should be given to patients on hemodialysis only intravenously, while subcutaneous application of -epoetin is recommended in patients before beginning the dialysis treatment and in patients on hemodialysis, or who had undergone kidney transplantation.
Author Pljesa, Steva
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Cites_doi 10.1056/NEJMoa011931
10.1182/blood.V98.13.3626
10.1016/S0140-6736(02)11544-3
10.1093/ndt/gfg182
10.1056/NEJM199608153350717
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Snippet There have been many publications in the past 20 years about positive effects of human recombinant erythropoietin, which is used in treatment of anemia,...
Introduction There have been many publications in the past 20 years about positive effects of human recombinant erythropoietin, which is used in treatment of...
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StartPage 254
SubjectTerms Anemia - etiology
Anemia - therapy
Erythropoietin - adverse effects
Humans
Kidney Failure, Chronic - complications
Kidney Failure, Chronic - therapy
Recombinant Proteins
Red-Cell Aplasia, Pure - chemically induced
Red-Cell Aplasia, Pure - diagnosis
Red-Cell Aplasia, Pure - therapy
Renal Dialysis
Title Possible complications of erythropoietin therapy in patients with chronic renal failure
URI https://www.ncbi.nlm.nih.gov/pubmed/15503795
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