Unexplained anaemia in older persons is characterised by low erythropoietin and low levels of pro‐inflammatory markers

Abstract

SummaryEpidemiological studies report that a third of the cases of anaemia in older persons is unexplained. We compared erythropoietin (EPO), inflammatory markers and major comorbidities between older subjects with normal haemoglobin levels and those with different aetiologic forms of anaemia, including unexplained anaemia. Participants were a representative sample of 964 persons aged ≥65 years, with no evidence of bleeding, complete blood tests, and a complete blood count within 6 h of phlebotomy. Anaemia was defined as haemoglobin <130 g/l in men and 120 g/l in women, and classified as a result of chronic kidney disease, iron deficiency, chronic disease and B12/folate deficiency anaemia, or unexplained anaemia based on standard criteria. Of the 124 anaemic participants, 42 (36·8%) had unexplained anaemia. Participants with anaemia of chronic diseases had significantly higher interleukin‐6 (IL‐6) and C‐reactive protein (CRP) levels, while those with unexplained anaemia had significantly lower CRP than non‐anaemic controls. Iron deficiency anaemia was characterised by significantly higher EPO levels compared with other types of anaemia and normal haemoglobin, B12 and/or folate deficiency. Unexplained anaemia was characterised by unexpectedly low EPO and low lymphocyte count. Unexplained anaemia is associated with reduced kidney EPO response, low levels of pro‐inflammatory markers and low lymphocyte counts.

Prevalence and determinants of anemia in the immediate postkidney transplant period

“…The observation of a direct association between donor age and Hb levels, independent of graft function, clearly suggests an age-related influence on the erythropoietin production capacity of the kidney. Although frequently hypothesized in the past, it has been shown only recently that anemia of unknown origin in the elderly might be caused by lower than normal erythropoietin levels [17].…”

“…One hundred and ninety-one of these 215 units (89%) were administered during the initial hospitalization. The first unit was administered on day 8 (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). The level of Hb triggering transfusion was 8.0 ± 0.8 g/dl.…”

Variability and heritability of hemoglobin concentration: an opportunity to improve understanding of anemia in older adults

“…18 Further, approximately one-third of anemia cases are not explained by nutrient deficiencies (iron, B12, or folate), renal insufficiency, or chronic inflamma- tion. [18][19][20] Although some of these cases might result from myelodysplastic syndrome, Guralnik and colleagues estimated that at least one-quarter of the anemia cases in older adults would remain unexplained. 18 While erythropoietin levels have been shown to increase with aging, 8 suggesting that decreased bone marrow response or red cell survival contributes to anemia in older adults, Ferrucci and colleagues demonstrated that erythropoietin levels and pro-inflammatory cytokines were significantly lower in older Italian adults with unexplained anemia compared to non-anemic persons.…”

“…18 While erythropoietin levels have been shown to increase with aging, 8 suggesting that decreased bone marrow response or red cell survival contributes to anemia in older adults, Ferrucci and colleagues demonstrated that erythropoietin levels and pro-inflammatory cytokines were significantly lower in older Italian adults with unexplained anemia compared to non-anemic persons. 20 The genetic contribution to unexplained anemia in older adults has not been defined. In view of the high prevalence of anemia in older adults and its association with adverse outcomes, an expanded research effort into the role of genetics in hemoglobin variability and anemia in older adults is warranted.…”

Pathophysiology of the aging kidney and therapeutic interventions

“…35 EPO levels are, however, unexpectedly suppressed in anemic elderly patients when compared with anemic young individuals, which suggests a blunted response to low hemoglobin levels. [36][37][38] Older women with osteoporosis and mild renal dysfunction exhibit lower calcium absorption rates and lower serum 1,25-dihydroxyvitamin D levels despite normal serum 25-hydroxyvitamin D levels, indicating a deficiency in the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by the aging kidneys. 39 Mild renal dysfunction (creatinine clearance less than 65 ml min À1 ) is an independent risk factor for falls and their associated fractures in older patients with osteoporosis.…”