Demography and laboratory medicine
The demographic changes in different parts of the world have led to a rapid increase in the elderly population. In 2010, approximately 5% (4.2 million) of the German population was 80 years old and older. By 2030, this cohort will rise by 48% and by 2060, will double to 8.8 million, meaning that one out of every 13 Germans will be over 80 years old .
Actual demographic changes go hand in hand with considerable social, economic and health-political challenges, as well as the changing medical care demands of the elderly and the old. This includes laboratory diagnostics in many ways, and therefore the topic of geriatric assessment in laboratory medicine might be of interest to our readers.
“Geriatric laboratory medicine” is not a defined specialized field but involves a variety of particularities that arise in the context of the laboratory diagnostics of elderly people, and should be taken into account for the adequate interpretation of laboratory test results in the young old (65–74 years), the aged (75–84 years) and the oldest old (>85 years) of our patients.
Age-related reference ranges for hematological and biochemical laboratory tests?
The decisive question is whether the commonly used reference values of distinct analytes and cut-off values are also valid in the elderly patient, taking into account that this cohort of patients – thanks to medical advances – is growing.
Children at different ages are comprehensively regarded as being physiologically different from adults and therefore age-dependent reference intervals were defined and accepted by the medical community. This is not the case in the elderly, although the aging organism undergoes serious physiological changes as well, perhaps on a more individual or even genetic basis. This explains differences in the results of biochemical or hematological tests in apparently healthy but aged individuals.
Many of the common reference values for biochemical or hematological tests are determined in young and healthy adults between the ages of 20 and 40 years. This means that their laboratory test results are compared with those from patients twice as old who have undergone around 40 years of physiological aging.
The validation of reference values for the three groups of young old, old and very old is a challenge in itself, because elderly people in perfect health are a rare species; most of them have health problems and are under regular medication. Therefore, it takes great effort to conduct reference value studies for this age group. The evaluation of reference values in geriatric populations in compliance with the regulations of the European guideline (CLSI EP28-A3c) was recently highlighted by Ozarda et al. .
Several well planned and comprehensively performed studies were published in the last decades, showing that many of the routine parameters seem to be valid in the elderly, too , , , , .
The “SENIORLAB Study in Quest of Healthy Elderly” , a new prospective cohort study of approximately 1500 healthy sexagenarians, reports the re-evaluation of reference intervals for more than 100 frequently used laboratory tests.
In this context, the hematological reference intervals are still under debate. Röhrig and co-workers performed a study on age-related hematological reference data, also published in this issue of the journal , which comes to the final conclusion that we do not need special age-related reference intervals for the elderly. Whether it is truly a final statement remains open in view of periodically published articles on the so-called anemia of the elderly.
The exponentially increasing number of anemic patients with increasing age raises the question of whether the World Health Organization (WHO) threshold for anemia-defining hemoglobin (Hb <13 mg/dL in men and<12 mg/dL in women) is also valid in the elderly. Demographic studies in north-eastern Germany showed that anemia will be the most frequent diagnosis in the rapidly growing population of the elderly and old .
On the other hand, the early diagnosis and effective treatment of anemia in older patients has a positive effect on their quality of life and mental performance, therefore keeping the current WHO thresholds possibly makes sense .
The causes of anemia in patients of advanced age are numerous: malnutrition is often associated with iron-, cobalamin- or folic acid deficiency; other causes are hematopoietic dysplasia, impaired renal function with modified erythropoietin (EPO) production, exhausted erythropoiesis and others . Nevertheless, approximately 30% of the diagnosed anemias in the elderly remain unexplained .
Age and impaired immune defense
With increasing age, the immune system becomes more susceptible to infections. Once acquired, the course of the infection is more severe and the clinical features are different when compared with younger patients. The overall mortality of infectious diseases increases with age: intraabdominal infections and also herpes zoster have a three times higher mortality as compared to young adults .
The background of impaired immune defense in the elderly can include a lower physiological reserve, a reduced immunological defense, chronical co-morbidities, an individually different response to therapy, an increased risk for nosocomial infections and an increased rate of therapeutic side effects, e.g. under antibiotic treatment.
Although vaccinations of the elderly are recommended, the older the patients are, the less effective the vaccination is.
New biomarkers and improved biochemical diagnosis of aging and age-related diseases
The search for valid markers of biological aging is an ongoing research field and the number of publications is rapidly increasing. These markers seem to be related to telomere length, a classic marker of aging, and to epigenetic aging. This research is also stimulated by the idea of finding markers which would allow the identification of individuals of comparable biological, not only chronological age. This should help to better standardize study groups for age-related studies.
Weber’s article  is dedicated to the laboratory diagnostics in patients with dementia, an emerging field for new biomarkers, allowing a better diagnosis and follow-up as well as a prognostic assessment. The current, commercially available marker tests are reviewed and critically commented by the author.
Age-related changes in drug metabolism and toxicity
Recently, in a review on pharmacokinetics and genomic variations in old age, it was concluded that environmental, physiological and epigenetic factors, and not genomic variations, modulate drug disposition in the elderly .
Combined with increasing multi-morbidity of older patients and the generally practiced polypharmacy, these factors might explain the increasing rate of unexpected drug effects. In addition, the age-related decline in renal function and the lower distribution volume for hydrophilic drugs in old patients and the relatively higher volume for lipophilic drugs are a daily challenge for the laboratory and physicians.
Pre-analytics in the elderly
Another aspect of laboratory testing in the elderly or old patients are challenges of preparing the geriatric patient for blood sampling and the sampling itself .
Older patients suffer from a disturbed sense of thirst and are often dehydrated when their blood is drawn for laboratory tests. The hematological test results indicate normality, but after restoring the liquid balance, the hematological test values indicate anemia.
The blood sampling itself is often aggravated by bad vein conditions, thus resulting in hematoma formation with consecutive local activation of coagulation factors, air aspiration causing hemolysis and the impossibility of correct filling special test tubes, e.g. for coagulation tests.
A further pre-analytical problem is the sampling of midstream or 24-h urine in old patients. There are unfortunately few studies on pre-analytical errors in the elderly, the old and the very old. Therefore, it seems necessary to develop recommendations for the management of typical pre-analytic pitfalls for the old.
Obviously the challenges for laboratory medicine in geriatric patients are complex and manifold and show particularities which deserve the increased attention of laboratory medicine. The contributions in this and future issues of JLM might stimulate further contributions as well as constructive and fruitful discussion and encourage further studies.
Present affiliation: Medical Diagnostic Institutes (Medical Care Centre), Sonnenburger Str. 70, 10437 Berlin, Germany
2. Ozarda Y, Higgins V, Adeli K. Verification of reference intervals in routine clinical laboratories: practical challenges and recommendations. Clin Chem Lab Med 2018. https://doi.org/10.1515/cclm-2018-0059.10.1515/cclm-2018-0059Search in Google Scholar
3. Adeli K, Higgins V, Nieuwesteeg M, Raizman JE, Chen Y, Wong SL, et al. Biochemical marker reference values across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey. Clin Chem 2015;61:1049–62.10.1373/clinchem.2015.240515Search in Google Scholar
4. Adeli K, Raizman JE, Chen Y, Higgins V, Nieuwesteeg M, Abdelhaleem M, et al. Complex biological profile of hematologic markers across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey. Clin Chem 2015;61:1075–86.10.1373/clinchem.2015.240531Search in Google Scholar
5. Huber KR, Mostafaie N, Stangl G, Worofka B, Kittl E, Hofmann J, et al. Clinical chemistry reference values for 75-year-old apparently healthy persons. Clin Chem Lab Med 2006;44:1355–60.10.1515/CCLM.2006.247Search in Google Scholar
10. Fenger S. Untersuchungen zur Veränderung des Morbiditätsspektrums einer alternden Bevölkerung am Beispiel des Bundeslandes Mecklenburg-Vorpommern. Universitätsmedizin Rostock, Medizinische Fakultät, Inauguraldissertation, 2012.Search in Google Scholar
11. Balducci L, Ershler WB, Krantz S. Anemia in the elderly – clinical findings and impact on health. Crit Rev Oncol Hematol 2006;58:156–65.10.1016/j.critrevonc.2005.09.003Search in Google Scholar PubMed
12. Berliner N. Anemia in the elderly. Trans Am Clin Climatol Ass 2013;124:230–7.Search in Google Scholar
13. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klen HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood 2004;104:2263–8.10.1182/blood-2004-05-1812Search in Google Scholar PubMed
14. Crossley K. Infectious in the elderly. In: Schlossberg D, editor. Clinical infectious disease. Cambridge: Cambridge University Press, 2008:643–6. Doi: 10.1017/CBO97805M2240.092.Search in Google Scholar
16. Dücker CM, Brockmüller J. Genomic variation and pharmacokinetics in old age: a quantitative review of age vs genotype-related differences. Clin Pharm Therap 2018 Mar 2. doi:10.1002/cpt1057. [Epub ahead of print].10.1002/cpt1057Search in Google Scholar
©2018 Walter de Gruyter GmbH, Berlin/Boston