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

Abstract

Epidemiological 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 > or =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.

Fig 1

Box-plots depicting interleukin-6 (IL-6), tumour necrosis factor α (TNF-α) and C-reactive protein (CRP) distributions in non-anaemic controls and participants with different clinical forms of anaemia. P-values were calculated from age- and sex-adjusted linear regression models. The central line within each box indicates the median value of the distribution and the top and bottom box limits are the 25th and 75th percentiles, respectively. The whiskers extend to the most extreme points located within 1.5 times the interquartile distance below and above the box. Points outside this range are singularly plotted as outliers. IDA, iron deficiency anaemia; ACD, anaemia of chronic disease; UAA, unexplained anaemia.

Fig 2

Box-plots depicting age-, sex- and haemoglobin-adjusted erythropoietin (EPO) levels according to anaemia status in non-anaemic controls and in participants with different clinical forms of anaemia. P-values were calculated from age-, sex- and haemoglobin-adjusted linear regression models. Description of the box-plots and abbreviations are given in Fig 1.

Fig 3

Scatterplot of the relationship between haemoglobin and erythropoietin (EPO) levels. EPO values are age and sex adjusted to enable comparison across the different forms of anaemia, which are indicated by circles of different colours (see legend). Abbreviations are given in Fig 1.