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Screening Tests For Latent Anemia In Hospitalized Adults Over 65
Author: Aurelian Udristioiu
Publisher: Emergency County Hospital TARGU-JIU
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Introduction

 

  Epidemiologic studies have suggested that anemia may be associated with poorer outcomes in a variety of disorders. In many studies the definition of anemia used is that suggested by a World Health Organization (WHO) expert committee over 40 years ago. The WHO criteria define anemia by hemoglobin (HGB) concentration of < 130 g/L for adult men and<120 g/L for adult females. [1]

      Results from the 1988-1994 United States National Health andNutrition Examination Survey (NHANES III) indicate that fewerthan 3% of adults aged 65 and older have hemoglobin levels below110 g/L, and therefore most anemia cases among community-dwellingolder adults are mild [2]. Nonetheless, recent evidence indicatesthat even mild anemia is independently associated with increasedrisk of recurrent falls, poorer physical function, hospitalization,and mortality in older adults. [3]

While a number of studies have reported differential distributionsof anemia by age and sex, less attention has been devoted todisparities in anemia by race. According to NHANES III estimates,older non-Hispanic blacks were 3 times more likely to have anemiacompared to older non-Hispanic whites (27.8% vs 9.0%). [1]. Similardisparities in anemia prevalence have been observed in otherpopulation-based studies of older blacks and whites.[4, 5]. These observations have led someto consider race-specific criteria for defining anemia. [6]

Anemia in the elderly is an extremely common problem that is associated with increased mortality and poorer health-related quality of life, regardless of the underlying cause of the low hemoglobin. A recent study in Iceland defined mild anemia as a hemoglobin concentration between 10.0 and 11.9 g/dL in women and between 10.0 and 12.9 g/dL in men [7]. This cross-sectional analysis provides evidence of anemia in 36.7% of hospitalized patients, and shows an association among anemia, poor nutritional status, and inflammation[ 8]. Future research on anemia in the elderly should focus on the age-

related physiologic changes underlying this condition and whether anemia correction can

reduce anemia-associated risks, and improve quality of life [9].

 

The purpose of this study was to determine the prevalence and causes of anemia among older adults hospitalized at an academic medical center.

 

 Method

 

    The prospective study consisted of 140 consecutive patients over age 65 (80 male, 60 female) hospitalized for stroke (n=25), chronic hepatic diseases (n=45), complications of atherosclerosis (n = 35), chronic cardiac disorders (n=20), or breast carcinoma (n=15), admitted in hospital after a preliminary ambulatory consult of specialist physicians. A second cohort of 40 patients over age 65 [25 males and 15 females] with chronic renal failure (prior to institution of hemodialysis) was also evaluated in the prospective study. Patients with evidence of acute or chronic blood loss were excluded from the study.  Laboratory tests were performed within the first 4-5 days of hospitalization in summer days of 2009 year. Diagnoses were established by the physicians caring for the patients. 

 

All patients had complete blood count (Coulter HMX with 22 parameters) and measurements of serum iron and iron binding capacity (Vitros 700). Reticulocyte count (RET %) was calculated after microscopic analysis of brilliant cresyl blue stained slides, (normal ranges adult: 0.5 - 1.5%). To evaluate rate of erythropoiesis, the Reticulocyte Production Index (RPI) was calculated using the formula: [RPI = RET% x HCT patient /45 /reticulocyte time maturation], where maturation time (reticulocytes survival days in

peripheral blood) was considered 1 day for  HCT 36-45%, 1.5 days for HCT 26-35%, 2 days for HCT 16- 25% and 2.5 days for HCT < 15% [10]. Reference interval for RPI in healthy individuals is 1.0-2.0; and RPI < 2 in a person with anemia indicates ineffective erythropoiesis, while values > 2 indicate compensation for decreased red cell survival (bleeding, hemolysis) [11].

 

In a control group of 40 apparently health adults (20 men and 20 women), reference values for CBC and iron status, were encompassed in Table 3 for this study.

 

Results

    

     Abnormal CBC results were common in hospitalized elderly individuals. Only 33 patients (23.58%) had normal results for all hematological parameters in the CBC, while another16 (11.4%) patients had normal HGB and HCT, but low MCV (average=72 fL, SD= 2.1) or MCH (average=24.3pg, SD= 1.6). Of the 91 anemic individuals, 63 (69.2%) had mild anemia (HGB decreased but > 106 g/L), while the remaining 28 (30.8%) had severe anemia.  All individuals in the group with severe anemia had low RET (mean 1.2%, range 0.5-1.5%), and RPI <1.4, indicating a hypo-regenerative type of anemia.

 

            The causes of anemia in this group of elderly individuals, determined by the treating physicians, are given in Table 2.  The most common cause of anemia was anemia of chronic disease, responsible for almost half of cases.  An additional 12% of patients had anemia felt due to breast cancer, but which had a laboratory picture similar to that seen in chronic disease anemia.  One-fifth of cases were felt due to chronic renal insufficiency and lack of erythropoietin production.  Only 15% of cases were due to iron deficiency, a common cause of anemia in younger individuals.  

 

In the cohort of older adult patients with chronic renal failure on dialysis, only 3 (7.5%) patients did not have anemia.  In contrast to the unselected group of elderly patients, in whom anemia was mild in the majority, more severe anemia was typical of the patients with renal failure. Of the total group of 40, over three-fourths had hemoglobin < 9 g/dL (7-8.9 in 23 patients (57.5%) and < 7 g/dL in 8 patients (20%)). [Graphic1]. As a group, the dialysis patients had normal RPI (mean 1.52), low TIBC (mean 225 mcg/dL), and normal saturation of transferrin (mean 29.1%).

 

In 72.50% of patients with anemia of renal chronic diseases associated with inflammations and normal erythropoiesis, HTC was in value of 29-25%, normal TIBC (average=282 micrograme/ d L, SD=2.5), low RPI in value of 1.33, low IST; 7.62% of cases with anemia in chronic renal diseases without inflammation but  ineffective erythropoiesis, and  HCT in value of 24-18%, was calculated low RPI, 1.21, normal TIBC(368 microgram/d L, SD =2.4) and low IST in value of 6.5%; to patients (19.88 %) with chronic renal diseases, was registered ineffective erythropoiesis and severe  IDA. Table 1

 

In three patients with no obvious cause of anemia, bone marrow aspiration was performed by sternal puncture. These patients also had neutropenia and thrombocytopenia, with blast count <5% in the peripheral blood, and macrocytosis. Morphologic abnormalities seen on bone marrow examination included bi-lobed or un-segmented nuclei (pseudo–Pelger-Huet abnormality) and granulation abnormalities in varying from and finally these patients were diagnosed as having myeloproliferative disorders.

 

Discussion

 

In a longitudinal study in healthy elderly subjects, HGB slowly but predictably declined with aging. An inverse relationship between hemoglobin and all-cause mortality was observed; the lowest risk for mortality occurred at hemoglobinvalues between 130-150 g/L for women and 140-170 g/L formen. The anemia is associated with an increased risk for hospitalizationand death in community-dwelling older adults. [9]

 

This study conforms that abnormal hematologic parameters are common in elderly individuals. [54.2% to men versus 40.6% to women ]. The most common cause of anemia was chronic disease anemia, which can include a variety of underlying disorders.  The peptide hormone hepcidin, secreted by the liver, controls plasma iron concentration by inhibiting iron export from macrophages and decreased absorption of iron from the intestine. Hepcidin is increased in anemia of chronic disease. [12].

 

Hypochromic, microcytic anemia due to iron deficiency (IDA) was an uncommon cause of anemia in the elderly patients in the current study (15%), while it is a common cause of anemia in younger individuals [13, 14].  In this study, the presence of hypochromic cells representing >10% of total RBC was considered functional iron deficiency (ID), when confirmed by low serum iron. Various cut off values for functional ID is reported in literature ranging from 2% to 10% hypocromic cells. [17] IDA must be differentiated from ACD [11] and thalassemia [12], which can also cause microcytosis.  Measuring TIBC is an indirect method of assessing transferrin, which is typically low in ACD, normal or low in thalassemia, and high in IDA.

 

Unexplained anemia is generally a condition of elderly persons. It appears more commonly with advancing age and is rarely, if ever, encountered in younger adults [15, 16]. Even with the advent of better tests such as serum ferritin, methylmalonic acid, and soluble transferrin receptor, a significant portion of elderly persons with anemia will continue to have unexplained anemia. Bone marrow examination, including staining for hemosiderin have been  be reccomanded in most elderly patients to determine if anemia is due to Myelodysplastic Syndrome. [17]

 

Conclusions

  

In elderly persons, the etiologies of anemia differ sufficiently from those in younger adults to warrant considering anemia in elderly persons as a distinct entity. In this study, anemia of aging was found in 65% of patients overall, and in over 90% of older adults with chronic renal failure.  Diagnosis of causes must rely on laboratory medicine results along with interpretation based on the clinician’s interpretation. Routine anemia screening using CBC is indicated in elderly hospitalized elderly, individually. An iron panel is useful in differentiating anemia of chronic disease from iron deficiency.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Statement of Funds

 

[1].Grant/Funding Support. -Not Applicable

 

[2] Financial disclosures. - Not Applicable

 

[3]. Acknowledgement- The author expresses his appreciation to D. Robert Dufour, M.D, AACC / NACB Director, for editing the manuscript.

  Address of correspondent: Doufour DR,  Veterans Affairs Medical Center, George Washington University Medical Center, Washington, DC. Address correspondence to the author at: 7311 Winterfield Terrace, Laurel, MD, 20707. Fax 202-745-8284; e-mail chemdoctorbob@earthlink.net

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

REFERENCES

 

 

 

1. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein 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; 104:2263–2268

 

2. Blanc B, Finch CA, Hallberg L, et al. Nutritional anemia: report of a WHO Scientific Group. WHO Tech Rep Ser 1968; 405:1–40.

 

3. Salive ME, Cornoni-Huntley J, Guralnik JM, et al. Anemia and hemoglobin levels in older persons: relationship with age, gender, and health status. J Am Geriatri Soc 1992; 40:489–4964

 

4. Zakai NA, Katz R, Hirsch C, et al. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med 2005; 165:2214–2220

 

5. Pan WH and Habicht JP. The non–iron-deficiency-related difference in hemoglobin concentration distribution between blacks and whites and between men and women. Am J Epidemiol 1991; 134:1410–1416

 

6. Beutler E and Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood 2006; 107:1747–175

 

7. Riva E, Tettamanti M, Mosconi P, Apolone G, Gandini F et al. Association ofmild anemia with hospitalization and mortality in the elderly: the Health and Anemia population-based study. Haematologica. 2009; 94(1):22-8

 

8. Ramel A, Jonsson PV, Bjornsson S, Thorsdottir I. Anemia, nutritional status, and inflammation in hospitalized elderly. Nutrition. 2008; 24(11-12):1116-22

 

9. Eisenstaedt R, Penninx BW, Woodman RC. Anemia in the elderly: current understanding and emerging concepts. Blood Rev. 2006; 20(4):213-26.

 

 10. Adamson JW, Longo DL. Anemia and polycythemia. in: Braunwald E, et al. Harrison's Principles of Internal Medicine. (15th Edition). McGraw Hill (New York), 2001

 

11. ACP CPSC Tools: Reticulocyte Production Index. American College of Physicians. Internal Medicine/ Doctor1s for Adults 1999, 2000

 

12. Knezevic V. Differentiation of Anemia from Chronic Diseases (ACD) with Anemia from Iron Deficiency (IDA).[ Abstract p136]. 10-16 Meeting of Balkan ClinicalLaboratory Federation 2008; p. 162

 

13. Thomas C, Thomas L. Biochemical Markers and Hematological Indices in Diagnosis

of  Functional Iron Deficiency. Clin Chem 2002; 48(7): 1066-1076

 

14. Bennett J M. Practical Diagnosis of Hematological Disorders.2th ed. Lett. Anemia of Chronic Diseases. Chicago: ASCP Press 2006; p. 615 – 671

 

15. Steensma DP, Tefferi A. Anemia in the elderly: how should we define it, when does it matter, and what can be done?. Mayo Clin Proc 2007; 82(8): 958-66.

 

16. Labbé RF, Dewanji A. Iron assessment tests: transferrin receptor vis-à-vis zinc.

ClinBiochem 2004; 37 [3]: 165-174

 

17. MediaLab. Course online. LabCE Quiz Game - Free Resource for Medical Technologists. Accessed 10/2009

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

HTC %

 

RPI

 

TIBC microgram/d L

 

IST %

35 - 30

1.52

225

29.1

29 - 25

1.33

282

7.62

24 - 18

1.21

368

6.5

 

Table 1. Correlation between Hematocrit (HTC), Reticulocytes Production Index (RPI) Total Iron Binding Capacity (TIBC) and Index Saturation Transferin (IST) in

Anemia of Chronic Renal Failure


 

 

 

 

 

 

 

 

 

 

 


Type of Diseases

Types of anemia

Frequency of anemia

Chronic disease/inflammation

Normocytic, normochromic anemia 

45%

Chronic kidney diseases without CRF

Hypochromic, microcytic anemia     

20%

Iron deficiency anemia

Hypochromic, microcytic anemia     

15%

Brest malignant diseases

Normocytic, normochromic anemia

12%

Thalassemia minor

Hypochromic, microcytic anemia       

4%

Myelodysplasic disorder

Macrocytic, normocromic anemia        

3%

Vitamin B-12 deficiency

Macrocytic, normocromic anemia    

1%

 

Table 2 Causes and prevalence of anemia to hospitalized elderly patients

 

 

 

 

 

 

 


 

 

 

 

 

 

 

 

 

 

Results of case

 

Reference Intervals

 

  Adult Females      

Reference Intervals

 

 Adult males      

White blood cell (WBC) count 3.9 x 109/L

4.4 - 11.3 x 109/L

4.8 - 10 x 109/L

Red blood cell (RBC) count 5.8 x 1012/L

4.1 - 5.1 x 1012/L

4.2 - 5.50 x 1012/L

Hemoglobin (HGB) 9.5 g/dL

12.3 - 15.3 g/dL

13 - 17 g/dL

 

Hematocrit (HCT) 36.5%

35.9 - 44.6%

42 - 52%

 

MCV 65.9 fL 80

81 - 99 pg

80 - 94 pg

 

MCH 20.9 pg

27.5 - 33.2 pg

 

27-31 pg

RDW 14.10

11.5-14. 5

11.5-15. 5

 

Platelets 275.0 x 109/L

140 - 450.0 x 109/

 

140 - 300 x 109/

Total serum iron 160 μg/dL

37 - 130 μg/dL

 

60 - 150 μg/dL

Iron-binding capacity 240 μg/dL

250 - 400 μg/Dl

250 - 400 μg/Dl

MCHC 28.3%

33.4 - 35.5%

 

32 – 36%

 

Table 3. Laboratory Test Results in on case of minor thalassemia.  The RBC count is increased for the amount of hemoglobin present. The concentration of hemoglobinin the RBC is slightly decreased (hypochromic) and the cells are small (microcytic). The variation in RBC size(RDW) is within normal limits.

 

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RECENT WORK OF RESEARCHES

 

1. Udristioiu A. The Assessment of Uncertainty in Measurement of Cholesterol; A Model of Calculation. Biophysical Journal; Volume 96, Issue 3, Supplement 1, February 2009; Page 504a.

2. Udristioiu A, Florescu Cristina, Popescu Manuela Andrei. “High Concentration of anaerobic ATP implicated in aborted apoptosis from CLL”. LabMedicine, American Journal of Clinical Pathology-ASCP, Manuscript 09-08-LM-S-SCI-0122R1, Published in 04-05/2010.

3. Aurelian Udristioiu. First Hematological Signal of Latent Anemia to Aging Population. Nature Publishing Group. Advance Search 0.1038 npre 2009.3285.1. Creative Common Attribution 3.0 License, accepted for the work online posted.

4. Udristioiu A, Cojocaru M, Florescu C. Screening Tests for Latent Anemia in Hospitalized Adults Over 65.   LabMedicine, American Journal of Clinical Pathology-ASCP, Manuscript  09-11-LM-S-SCI-0156.R1,  Published  in 07-05/2010.USA American Journal of Clinical Pathology p-ISSN: 0002-9173 ICV 38.53 LabMedicine ; Ascp Press) , Impact Factor ISI, IF = 2.853 , 18 Index Copernicus Journals Master List 2006.

5. PHENOTYPIC AND GENOTYPIC CHARACTERIZATION OF ANTIBIOTIC RESISTANCE PATTERNS IN ACINETOBACTER BAUMANNII STRAINS ISOLATED IN A ROMANIAN HOSPITAL. MANUELA-ANDA RADU-POPESCU1*, SILVIA DUMITRIU2,SIMONA ENACHE-SOARE3, GABRIELA BANCESCU2, AURELIANUDRISTOIU4, MANOLE COJOCARU5, CODRUTA VAGU6

1 University of Medicine and Pharmacy “Carol Davila, Faculty of Pharmacy, Department of Microbiology, Traian Vuia 6, Sect. 2, 020956,Bucharest, Romania. 6“Stefan S. Nicolau” Virology Institute, Bucharest, Romania. FARMACIA 2010; (57); 3: 420-427 IMPACT FACTOR ISI THOMSON 0.144 .

6. Moleular Biological  Tchiniques  user for identification  of Candida SPP. MANUELA-ANDA RADU-POPESCU1*, SILVIA DUMITRIU2, SIMONA ENACHE-SOARE3,  AURELIAN UDRISTOIU4. 1 University of Medicine and Pharmacy “Carol Davila, Faculty of Pharmacy. FARMACIA 2010; (58); 4: 422-429

7. Udristioiu A. Role of Mg2+ ion as cofactor ATP in assurance of energetic environment cells( Abstract). Magnesium Research 2011; 24 (1): 22-6.

8. -Aurelian Udristioiu, Radu G. Iliescu, Cristina Popescu. Variability of bilirubin values in serum samples with high triglycerides; interference or congenital liver syndromes. J Biosci Tech Volume 2, Issue 4 (JULY 2011).

9. Aurelian Udristioiu¹*,Radu G. Iliescu², Lucian Udristioiu¹ and Manole Cojocaru. A new approach of abnormal apoptosis as a cause of autoimmunity and malignancy. Biotechnology and Molecular Biology Review Vol. 6(8), pp. 166-171, November 2011 . Available online at < http://www.academicjournals.org/BMBR>

10. Aurelian Udristioiu, Cristina Popescu, Manole Cojocaru, Sorina Comisel, Valentina Uscatescu. Relation between LDH and Mg as Factors of Interest in the Monitoring and Prognoses of Cancer. Journal of Bioanalysis & Biomedicine. Ref.:  Ms. No. JBABM-11-48R1 accepted on Jan 27, 2012

11. UDRISTIOIU A. Florescu C, Popescu C, Cojocaru M "Significance of Neutrophil Alkaline Phosphatase versus Isoenzymes ALP in Acute or Chronic Diseases,"accepted for publication in LabMedicine, LabMedicine Manuscript 11-03-LM-U-MR-0052.R2/11/12/2011.

12. Aurelian Udristioiu¹, Radu Iliescu ², Manole Cojocaru³. Errors in Counting Platelets in Hemodialysis Patients by Use of Optical Microscopy. Review of Applied Physics (RAP) Volume 2 Issue 1, March 2013; p: 17-22

13. Aurelian Udristioiu¹, Radu Iliescu ², Manole Cojocaru³. Energetic Levels of Metabolic Pathways in Malignant B and T Cells Mini-Review. Advances in Chemical Science Volume 2 Issue 4, December 2013; 2; 90-95

14. Aurelian Udristioiu¹, Manole Cojocaru² Hemolytic Anemia Drugs Induced by Antihypertensive Agents: A case of Laboratory. 13 Scholars Journal of Medical Case Reports ISSN 2347- 6559. Sch J Med Case Rep 2013; 1(1):8-11

15. Aurelian Udristioiu1*, Radu G. Iliescu2, Manole Cojoraru Molecular mechanisms of bone reconstruction in new dental implant technology. Integrated Journal of British. Volume 1 2014 Issue 1(5-6), pg: 1-7; IJBRITISH.

WRITEN BOOKS:

1.Aurelian Udristioiu. Cicloergometrul si Sanatatea. Ed. Medicala 1990, Bucuresti. ISBN: 973-39-01105-9; Formatul 16/10 x 100; Nr pagini: 78.

2.Aurelian Udristioiu. “Bioenergetica Celulara si Maligna” Ed. Academica Brancusi 2002, Targu Jiu, Bun de tipar, Bucuresti, Tipografia Everest 2001; ISBN 973 85342-6-7; Formatul 16/14 x 100; Nr. Pagini: 307.

3. Aurelian Udristioiu, Manole Cojocaru, Radu Iliescu., Hematological and Metabolic Aspects from Laboratory Medicine" (ISBN 978-3-8473-0775-4). LAP LAMBERT Academic Publishing GmbH & Co. KG Heinrich-Böcking-Str. 6-8 , 66121, Saarbrücken, Germany, 2012.

4. Book title: Renal Diseases / Book 2 (ISBN 979-953-307-704-7). Chapter title: Variability of Biological Parameters in Blood Samples between Two Consecutive Schedules of Hemodyalsis

Authors: Aurelian Udristioiu, Manole Cojocaru, Victor Dumitrascu, Daliborca Cristina Vlad, Alexandra Dana Maria Panait and Radu Iliescu, Publishing Group 2011., Volume 2, Issue 4 (JULY 2011)

5. e-BOOK: Hematological and Metabolical Aspects of Laboratory Medicine (Hematological and Metabolical Aspects from Laboratory Medicine) ( Second Edition ) [Large Print] [Paperback].

 

Publisher: Aurelian Udristioiu, 2 edition (September 9, 2013) Full Color on White paper, 122 pages. ISBN-13: 978-1492186816 (CreateSpace-Assigned) ISBN-10: 1492186813, BISAC: Medical / Laboratory Medicine, USA. Sold by www.amazon.com  

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