Erythropoietin in Elderly Patients with Anemia of Unknown Etiology
Bibliographic record
Abstract
Abstract Background: The underlying etiology of anemia is unclear in a large proportion of elderly patients. The term "anemia of unknown etiology" (AUE) applies when investigations do not suggest a specific cause. It has been suggested that erythropoietin (EPO) may be relatively decreased in patients with AUE but previous studies have been limited by methodological considerations. To address this question we investigated the EPO response in elderly patients with AUE in comparison to other etiologies in a large cohort. Patients and methods: We conducted a retrospective cohort study including all consecutive hematology patients referred to our center and who had EPO levels determined between 2005 and 2013. We included patients 60 years or older who met the World Health Organization criteria for anemia (<130 g/L in men, <120 g/L in women) excluding patients with insufficient electronic medical records. Three reviewers independently adjudicated each patient's anemia to one of ten diagnostic groups (chronic kidney disease [CKD], iron deficiency anemia [IDA], anemia of chronic disease [ACD], myelodysplastic syndrome [MDS], AUE, suspected MDS, vitamin B12 deficiency, folate deficiency, other etiology, or multifactorial) using predetermined criteria. The etiology reported by at least two of the three reviewers was used in the analysis, with differences resolved by consensus. Inter-observer agreement was assessed using Kappa and Fleiss' Kappa statistics. Patients with IDA served as the reference group. EPO levels were compared between groups using unpaired t-tests. To adjust for potential confounders we constructed stepwise linear regression models in order to estimate the effect of each etiology on EPO level compared to the reference group. Models were adjusted for hemoglobin level, glomerular filtration rate (eGFR) and comorbidity using the Charlson Comorbidity Index. EPO concentration was log transformed to maintain the assumption of homoscedasticity. Regression coefficients were back-transformed using the exponential function and thus they represent the ratio of EPO for each given etiology relative to the reference group. Results: Of 1511 potentially eligible patients, 570 met our inclusion criteria. Diagnostic groups with 20 or less patients were excluded and thus 531 patients were included in the final analysis. The mean age was 75.7 years and 60% were male.The mean Charlson Comorbidity Index was 1.5. Inter-observer agreement for diagnostic categories was adequate. Compared to IDA, EPO was significantly lower in CKD, ACD and AUE, and higher in MDS and other etiologies. The results remained significant for CKD, ACD and AUE after adjusting for hemoglobin and eGFR, but not for MDS and other etiologies (Table). The effect of comorbidity on the models was negligible in all analyses and thus this data is not shown. Conclusion: Our results suggest that the EPO response is inadequate in elderly patients with AUE even after accounting for hemoglobin and renal function. This suggests that decreased EPO production or a blunted EPO response to anemia may play a role in the pathogenesis of AUE and that this may indeed constitute a distinct entity. Further studies exploring the potential mechanisms and clinical interventions are warranted. Table 1. Mean Erythropoietin Levels and Regression Analysis Diagnostic group N Erythropoietin (IU/L) Linear regression models Unadjusted Adjusted for Hb Adjusted for Hb and eGFR Mean P-valuea Coefficient (95% CI) Coefficient (95% CI) Coefficient (95% CI) Iron deficiency 59 102.4 - Ref. Ref. Ref. Chronic kidney disease 33 31.2 0.001 0.29 (0.18 - 0.48) b 0.29 (0.19 - 0.46) b 0.47 (0.27 - 0.81) b Chronic disease 31 26.8 < 0.001 0.42 (0.27 - 0.66) b 0.49 (0.33 - 0.72) b 0.55 (0.38 -0.79) b Myelodysplastic syndrome 180 287.8 0.002 1.68 (1.11 - 2.56) b 1.32 (0.93 - 1.87) 1.34 (0.95 - 1.87) Anemia of unknown etiology 110 38.2 0.003 0.43 (0.32 - 0.59) b 0.62 (0.46 - 0.83) b 0.73 (0.55 - 0.97) b Other etiologies 118 271.4 0.002 1.36 (0.86 - 2.15) 1.10 (0.75 - 1.60) 1.11 (0.77 - 1.58) a For the comparison with iron deficiency using a Student's t-test b P < 0.05 Disclosures Lazo-Langner: Bayer: Honoraria; Pfizer: Honoraria.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".