AUCTORES
Globalize your Research
Case Report
*Corresponding Author: : Awad Magbri, MD, FACP, Mariam El-Magbri, MPH & Pablo Abrego Hernandez, MD Marshfield Medical Center, Weston, WI.
Citation: Awad Magbri, (2022) Anemia Caused by Erythropoietin Stimulating Agent in End-stage Kidney Disease Patient PRCA (pure red cell aplasia) (Case presentation and review of the literature). J. Pharmaceutics and Pharmacology Research, 5(9); DOI:10.31579/2693-7247/108
Copyright: © 2022 Awad Magbri, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 28 October 2022 | Accepted: 09 November 2022 | Published: 08 December 2022
Keywords: pure red cell aplasia (prca); eskd (end-stage kidney disease); hemodialysis; peritoneal dialysis
We reported a case of severe anemia in a patient with end-stage kidney disease (ESKD) on dialysis. The anemia developed when the patient is switched from hemodialysis (HD) to peritoneal dialysis (PD) when the intra-venous erythropoietin stimulating agent (ESA, Epogen) was changed into subcutaneous injection of darbepoetin. The patient’s hemoglobin has dropped 2 grams in about two months during this period (table 1). Extensive work-up including, bleeding disorders, hemolysis, iron deficiency, infections including CMV, Epstein-Bar virus, parvo-19 virus infection were unrevealing (table 1). The anti-Epogen neutralizing antibodies were not measured due to unavailability. Bone marrow biopsy and aspirate were negative for infiltrations or myelodysplastic syndrome (MDS). The leukocyte and platelets counts were normal. Even though anti-ESA antibodies were not measured in this case, all tentative causes of his anemia were excluded by laboratory investigations. The patient’s anemia was treated symptomatically with blood transfusion and discontinuation of the ESA treatment. He made a remarkable recovery.
Pure red cell aplasia (PRCA) is a syndrome characterized by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction in the erythroid precursors in the bone marrow. The white blood cell and the platelet counts are usually normal.
Acquired PRCA is a primary disorder or secondary to some other causes. The primary acquired PRCA is an autoimmune disorder that is antibody mediated. Many cases of acquired PRCA are idiopathic. Secondary acquired PRCA may be associated with collagen vascular/autoimmune diseases such as systemic lupus erythematosus; lymphoproliferative disorders such as chronic lymphatic leukemia or lymphoma; infections, particularly with parvovirus B19; thymoma and other solid tumors. Other toxins and drugs are sometimes implicated as a cause of PRCA, like chloramphenicol, rifampicin, phenytoin, azathioprine, and isoniazid [1]. PRCA has been described in patients treated with epoetin and other erythropoiesis stimulating agents (ESAs), stemming from the induction of neutralizing antibodies directed against the ESA molecule [2]. Most reported cases have been in patients receiving ESA for chronic kidney disease- related anemia. The aim of presenting this case is to draw attention to the possibility that rare causes of anemia in patients on dialysis must be considered and ruled out before embarking on symptomatic treatment.
Myelodysplastic syndrome can uncommonly be presented as PRCA and must be excluded by bone marrow aspirate and flow cytometry. Cyclosporin with or without corticosteroids, appears to be the single most effective immunosuppressive agent used in the treatment of PRCA.
A 63-year-old Caucasian male, with past medical history significant for hypertension, T2DM, stroke, and severe anemia. His anemia was responsive to intravenous Epogen when he was started on hemodialysis (HD). Then he developed a precipitous decrease in his hemoglobin over a period of eight weeks. His reticulocyte count was low, and his iron stores were normal. The abrupt decrease in his hemoglobin occurred when darbepoetin is switched to subcutaneous injection for his anemia treatment (table 1).
His physical examination revealed an obese man with no significant shortness of breath, alert and oriented x 3. His heart, chest and abdominal examination were unremarkable. He has mild lower extremities edema.
He was started on HD for his ESKD in May 2022 via a tunnel dialysis catheter in the right internal jugular vein. He then switched to peritoneal dialysis (PD) in June 2022. He was on Epogen intravenous injection while he was on HD. When he was switched to PD, his Epogen is replaced by Darbepoetin subcutaneously.
A CT scan of the abdomen and pelvis failed to show any retroperitoneal bleeding or lymphadenopathy. During the interim time he received blood transfusion to maintain his HgB in the normal range. His hemoglobin dropped from 10.8 to 6.5g/dl in 8-12 weeks, (table 1). Despite extensive work-up for bleeding including upper and lower endoscopy and screen for infection, no cause was found to account for his anemia (table 1). There was no evidence of hemolysis also to explain his precipitous decline in the HgB (table 1).
His bone marrow examination revealed normal WBC and platelets precursors with marked reduction of the red blood cell precursors. No evidence of bone marrow infiltration was found, pictures is not available. Although, the anti-EPO antibodies were not measured due to unavailability. Given the clinical pictures and the fact that he has developed only anemia with normal iron stores, white cell count, and platelet count, marked reduction of the reticulocyte count and with no evidence of bone marrow disease, PRCA was considered the plausible cause of his anemia. No immunosuppression was started based on the recommendation of the hematologist. The patient’s anemia was treated symptomatically with blood transfusion and discontinuation of the ESA treatment. He made a remarkable recovery.
Table 1: WBC – white blood cell count RBC – red blood cell count Hgb – hemoglobin HCT – hematocrit TIBC – total iron binding capacity Ng/ml – nanogram per milliliter
The diagnosis of PRCA rests on excluding other causes of normocytic normochromic anemia with normal white cell and platelets counts. In PRCA, the reticulocyte count and the reticulocyte index should be low with marked reduction in the red cell precursors in the bone marrow, in a patient who received ESA injections for his/her anemia.
Most cases of non-erythropoietin (EPO) related PRCA are mediated by IgG autoantibodies or cytotoxic T lymphocytes directed against erythroid precursor or progenitor cells [1,3]. PRCA against endogenous EPO is rare in patients who have never been treated with ESA [4-6].
Several preparations of ESA produced by various manufactures differ from each other by the degree of glycosylation and sialic acid content [7]. The vast majority of PRCA occurred in patients who are treated with epoetin alfa (Eprex, in single-use syringes) which are used outside the United States. EPO-related PRCA has been described with other preparations including darbepoetin alfa and methoxy polyethylene glycol-epoetin beta [8,9].
Almost all reported cases of anti-EPO antibody-mediated PRCA have occurred in patients with chronic kidney disease (CKD) who have received the drug subcutaneously (2,10-12). Reports of anti-EPO antibody mediated PRCA have occurred in patients in Canada, Australia, and Asia [11,13]. The condition remains extremely rare, given the widespread use of EPO and other ESA in treating patients with anemia of chronic disease [14,15]. The reported incidence of PRCA occurring with subcutaneous exposure of ESA is estimated to be 1.6 per 10,000 patient-years [16]. There have been over 200 reported cases of PRCA cases caused by Eprex use representing most reported PRCA cases [11,13,17]. Fortunately, EPO PRCA has become exceedingly rare after the modification of the EPO backages [18].
Development of anti-EPO non-neutralizing and neutralizing antibodies has occurred in Thailand related to subcutaneous use of product manufactured and used outside the United States [19-22]. Based on Canadian studies the routine screening for anti-EPO antibodies cannot be justified given the rarity of the conditions [23,24].
The 2012 kidney Disease: Improving Global Outcome (KDOGO) guidelines, suggest evaluation for PRCA due to anti-EPO antibodies should occur in a patient exposed to at least eight-weeks of ESA therapy who develops all the following [25]:
Elevated serum transferrin saturation and serum ferritin, reflecting decrease utilization of iron secondary to diminished erythrocytosis which can be a clue to the occurrence of PRCA.
Evaluation of PRCA consists of a bone marrow aspirate examination and assessment for the presence of anti-EPO antibodies. Bone marrow aspirate reveals severe erythroid hypoplasia, with <5>
Both neutralizing and non-neutralizing anti-EPO antibodies may be present and can cause the PRCA (31). The availability of these tests differs in different parts of the world. It is recommended if you suspected the diagnosis of PRCA to send the blood samples to the ESA-manufacture, where different test can be performed (27).
There is limited experience with managing PRCA, but the following have been used
Patients who received cyclophosphamide or cyclosporin with or without steroids have the best results. The fastest response occurred with the use of cyclosporin (28-31). Continuation of treatments with corticosteroids and immunotherapy should be accomplished until the anti-EPO antibodies become undetectable.
The treatment can be discontinued in patients who do not respond in 3-4 months after initiation of therapy. Monitoring reticulocyte count and anti-EPO antibody levels every 1-2 weeks during treatment is recommended.
Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a novel class of oral drugs that stimulate the production of endogenous EPO. These drugs can be helpful for the management of anemia in patients with EPO-associate PRCA (32-35).
Patients who develop normocytic normochromic anemia while on ESA with normal WBC, platelet count, and normal iron stores should be investigated for bone marrow failure or PRCA. PRCA is characterized by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction in the erythroid precursors in the bone marrow. The white blood cell and the platelet counts are usually normal. Most cases of EPO-related PRCA are due to anti-EPO antibodies. Treatment consists of discontinuation of ESA, transfusion of RBCs as necessary for anemia, immunosuppression to eradicate the antibodies, and at times kidney transplant in patients who are transplant candidates.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
