Senior Labor Study: A New Definition Of Normal Hemoglobin Values In Older Healthy Individuals

With increasing mean age of the world population it becomes clear that biological and chronological ages might diverge on individual levels. In contrast to working age adults, older people have a higher incidence of anemia mostly in association with medical comorbidities (Artz, Fergusson et al. 2004, Merchant and Roy 2012). Incidence of anemia in the elderly has so far been investigated in large studies mostly performed on hospitalized patients, nursing homes subjects or mobile examination centers subjects seeking medical care with a variety of complaints (Kikuchi, Inagaki et al. 2001, Guralnik, Eisenstaedt et al. 2004). In the USA, the 3rd NHANES study focused on racial groups of elderly revealing a prevalence of anemia in men and women >65 yrs of ∼10% (Izaks, Westendorp et al. 1999, Guralnik, Ershler et al. 2005). In patients over 85 yrs, this number exceeded 20%.

Current reference intervals for clinical laboratory assays are based on younger adult's samples. Physiologic concentrations of hemoglobin (Hb) in human blood range from 120 g/l (female) and 130 g/l (male) to 168 g/l (both genders) under which anemia and above which polycythemia get diagnosed. We are currently in need for reference ranges suited for normal older subject and unbiased by already debilitated individuals. The defining cut-offs provided by the WHO are 120 g/l for women and 130 g/l for men (WHO Technical Report Series 1968); although older age is generally associated with lower Hb levels, these cut-offs do not account for age.

We have performed a large recruitment as part of our Senior Labor study (Risch, Medina et al. 2012). In contrast to previous studies, we have prospectively recruited healthy Caucasian subjects over 60, implementing strong exclusion criteria for participating subjects. For those healthy individuals, a complete blood count (CBC) as well as frequently performed clinical laboratory tests were prospectively performed.

A total of 1255 subjects consented to enroll for the study after having passed the primary clinical exclusion criteria which comprised one or more of the following questions affirmatively answered (primary exclusion criteria): drugs: do you take drugs containing steroids, are you under ill-adjusted antihypertensive therapy, do you suffer from thyroid diseases/are you substituted with thyroid hormones, do you have diabetes mellitus, have you suffered from cancer during the last 5 years, were you hospitalized during the month prior to enrolment and do you abuse alcohol.

Complete blood count assays were done using an XE-5000 hematology analyzer and clinical chemistry assays followed routine workflow on modular platforms.

We evaluated 696 women and 559 with ages ranging from 60 to 99 years old. Mean Hb and 95% confidence intervals were calculated using logarithmic transformation in order to correct of skewness of the data. Overall, women had a mean Hb of 136 (95%CI 120-155) and men had a mean Hb of 148 (95%CI 128-172). Detailed results by age groups are presented in figure 1.

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Hb level was steady over age groups until 74 yo for men and 79 for women. Interestingly, only a few subjects fell outside the WHO limits with 20 women having a Hb less than 120 (2.9%) and 20 men a Hb less than 130 (3.6%).

We looked for frequent causes for anemia such as low ferritin and vitamin deficiencies (folic acid and B12). In the cohort, 37 subjects had a ferritin lower than 20 µg/l (2.9%). Among these, 9/37 (24.3%) had a low Hb (WHO definition) and only one in 37 (2.7%) had a MCHC below 310.

The micronutrients folic acid and vitamin B12 were also assessed; 98 subjects (7.8%) had folic acid < 10 nmol/l. Among these individuals, 6/98 (6.1%) were anemic. The definition of vitamin B12 deficiency varies but is usually accepted as lower than 200 pmol/l in older persons: in the whole population, 398/1255 (31.7%) subjects had vitamin B12 levels < 200 pmol/L, and 105/1255 (8.4%) had vitamin B12 concentrations less than 150 pmol/L. Using these two limits, these subjects were anemic in 11/398 (2.8%) and 4/105 (3.8%) respectively. This indicates a limited impact of folic acid and B12 deficiency on anemia of the elderly.

In this study, we were able to define new Hb reference range in older subjects reporting healthy by strict clinical criteria in a large cohort of subjects. Our results show a very limited proportion of subject with WHO defined anemia, thus indicating that even in older subjects, the discovery of a low Hb is likely to be associated to an underlying pathology.