Erythropoietin Levels in Elderly Patients with Anemia of Unknown Etiology.
BACKGROUND
In many elderly patients with anemia, a specific cause cannot be identified. This study investigates whether erythropoietin levels are inappropriately low in these cases of "anemia of unknown etiology" and whether this trend persists after accounting for confounders.


METHODS
This study includes all anemic patients over 60 years old who had erythropoietin measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient's anemia to one of ten etiologies: chronic kidney disease, iron deficiency, chronic disease, confirmed myelodysplastic syndrome (MDS), suspected MDS, vitamin B12 deficiency, folate deficiency, anemia of unknown etiology, other etiology, or multifactorial etiology. Iron deficiency anemia served as the comparison group in all analyses. We used linear regression to model the relationship between erythropoietin and the presence of each etiology, sequentially adding terms to the model to account for the hemoglobin concentration, estimated glomerular filtration rate (eGFR) and Charlson Comorbidity Index.


RESULTS
A total of 570 patients met the inclusion criteria. Linear regression analysis showed that erythropoietin levels in chronic kidney disease, anemia of chronic disease and anemia of unknown etiology were lower by 48%, 46% and 27%, respectively, compared to iron deficiency anemia even after adjusting for hemoglobin, eGFR and comorbidities.


CONCLUSIONS
We have shown that erythropoietin levels are inappropriately low in anemia of unknown etiology, even after adjusting for confounders. This suggests that decreased erythropoietin production may play a key role in the pathogenesis of anemia of unknown etiology.
Department of Medicine, Division of Hematology, Western University, London, ON, Canada.
Zachary
http://orcid.org/0000-0002-3710-1193
Z
Gowanlock
Department of Medicine, Division of Hematology, Western University, London, ON, Canada.
Swetha
S
Sriram
Department of Medicine, Division of Hematology, Western University, London, ON, Canada.
Alison
A
Martin
Department of Medicine, Division of Hematology, Western University, London, ON, Canada.|Department of Oncology, Western University, London, ON, Canada.
Anargyros
A
Xenocostas
Department of Medicine, Division of Hematology, Western University, London, ON, Canada.|Department of Oncology, Western University, London, ON, Canada.|Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
Alejandro
A
Lazo-Langner
D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D015897:Comorbidity; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D005494:Folic Acid Deficiency / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D005919:Glomerular Filtration Rate; D006403:Hematologic Tests; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D012189:Retrospective Studies; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology
D015415:Biomarkers; D006454:Hemoglobins; D004921:Erythropoietin