Managing Anemia in

Elderly
Dr. Smita Gupta
Prof. & HOD
Dept. of General Medicine
SRMS Institute of Medical Sciences, Bareilly
Introduction
Definition
Epidemiology
Clinical features
Etiopathogenesis
Types of Anemia
Microscopic pattern
Grade of anemia
Treatment
Take home message
 INTRODUCTION

 Anemia- a public health issue old age - a clinical challenge

Hemoglobin declines with advancing age
Elderly > 65 year age (biological age)
 Early Elderly – till 74 years Late Elderly > 75 years

 Worldwide both the number and ratio of older adults growing

 Globally 703 million adults in 2019, by 2050- 1.5 billion

 Elderly population, from 17.66% to 20.78% in last decade (Europe)

 Share of > 80yr age population expected to increase from 5.9 %- 14.6%

(United Nations :world population aging 2019) (Klara Gado et al 2022)

 INTRODUCTION
IN INDIA
 Elderly population - 8.6% in 2011
-10.1% in 2021
- 13.1% in 2031

 Anemia is most frequent in old age , prevalence =17% in age above

>65yrs (Gaskell H et al)

 Prevalence of anemia- as per various population study

2.9%-61% for - Men
3.3%-41% for - Female

(Juarez-Cedilla et al 2014)
 EPIDEMIOLOGY
Study Prevalence of anemia

Juarez-cedilla et al 2.9-61% for males

( various studies) 3.3-41% for females

Gaskell H et al 12% in community

(systemic review of 34 studies- 40% in hospitalised
85,409 indivl) 47% in nursing homes

Zaninettiet et al 62% M/ 60.1% F (>65 yrs)

(2018- Italy, admitted pts) 44.1% M/ 53.5% F (<65 years)
 COMPLICATIONS

Geriatric anemia may be associated with :

Increased Decreased Frequent Reduced

risk of physical/cogn and execution
.fracture
itive
longer physical
performanc performance,
and CV e & impaired stay in increased
disease mood hospital mortality
ANEMIA & HEALTH CARE COST
 Impact of anemia on HRQOL has been vastly studied

 A large cohort study of 138670, >60 y anemia was a/w poor QOL
as compared to < 60 y (Wouters H et al)

 Use of healthcare resources are exacerbated in older people

 Doubling of medical cost as to non anemic (Nissenson et al)
 Hospital stay prolonged (Zaninetti et al 2018)
 Length of stay increased to 4-5 days with moderate anemia
 7-10 days in severe anemic cases. (Dharmrajan et al)
 DEFINITION OF ANEMIA
 According to WHO criteria “Anemia was defined as hemoglobin
<12 g/dL in women and <13 g/dL in men and absolute iron deficiency
was defined as a serum ferritin <30 ng/mL”.

 This definition has been used in majority of studies conducted in older age.

 NHANES III (33,994) and Scripps Kaiser database has however

suggested a higher reference values to define anemia in elderly

 Cardiovascular Health cohort Study (2005)(5888) have described Hb of

>13.7g in men and >12.6g in females with better survival
. In 11yrs follow up.
 TYPES OF ANEMIA
No sub classification of anemia present in elderly

1. Anemia from nutritional deficiency

2. Anemia due to renal diseases
3. Chronic disease or inflammation (CI)
4. Unexplained anemia (UA), in the absence of other specific
causes.
*Clonal haematopoiesis/CCUS

Significant no (30-50%) is known to be multifactorial.

(Petrosyn et al)
 ANAEMIA OF NUTRITIONAL
DEFICIENCY
 Apprx 1/3rd of anemia in elderly is due to nutritional deficiency

(Guralnik et al 2004)
IDA alone accounts for ½ the cases
 Vitamin B12 def – 11.4-25.3 % Folate def – 4.6%-10.55%
(Bianchianemia
Iron deficiency VE et al 2014)
B12 deficiency anemia
Low iron content in diet Malabsoprtion due to H.
pylori
Decreased absorption Coeliac disease
Chronic GI blood loss Pernicious anemia
Gastritis, esophagitis, FCM (food cobalamine
PUD, colorectal CA, malabsorption)
angiodyspalsias
Use of NSAIDs Vegetarian diet
 ANAEMIA OF NUTRITIONAL
DEFICIENCY
Polymedication was considered independent risk factor for anemia, a
12–35% higher chance of anemia was seen in aspirin users alone.

Other drugs like corticosteroids and anta-acids were also seen

associated with IDA

Screening for under nutrition should be included in assessment of

anemia in geriatric patients as low serum albumin levels are found as
independent risk factors for anemia in geriatric patients

 Other causes of anemia is due to deficiency of copper, selenium,

ANAEMIA OF CHRONIC Ds /CKD /CI
Anemia of CD / AI accounts for approx. 1/3 rd cases of anemia in elderly
(Balducci et al)

Chronic conditions -infections, CHF, diabetes, malignancy, IBD or RA,

advanced atherosclerosis

Inhibition of erythropoiesis by inflammatory cytokines,

TNF, IL-1 which inhibit the production and action of EPO
and blunted response to erythroid progenitors to EPO

MECHANISMS Increased uptake and retention of iron in RE cells

leading to iron restricted erythropoiesis through over
expression of Hepcidin

Increased erythrophagocytosis and reduced survival of

circulating RBCs
 INFLAMMAGING
Additionally there is concept of a proinflammatory state or
“inflammaging”- a model which explains high prevalence of
anemia with age disorders like sarcopenia, asthenia and
frailty.

The term used by Franceschi et al in year 2000 to describe

low grade proinflammatory state associated with aging
process.

There is chronic upregulation of inflammation with increased

levels of proinflammatory cytokines levels.
 UA – UNEXPLAINED ANEMIA
 In wide range population based study 25-44% cases were
classified as UAA (Jack Guralink et al 2022)
 Unidentified causes are referred to as Unexplained Anemia
 1/3rd of all anemias in elderly
Causes of UAA: likely multifactorial
• Androgen deficiency
• Low EPO levels
• Malnutrition- low albumin, low Vitamin D
level

Diagnosis of UAA-
• Normal lab parameters
• Diagnosis of exclusion when nutritional,
inflammatory and renal disease ruled out
• Including bone marrow examination
 UNEXPLAINED ANEMIA
Prevalence (%) Authors name, year
36.8% Ferrucci L et al., 2007 [64]
43.7% Artz AS et al. 2011 [23]
35% Willems JM et al., 2012 [49]
5.8% Wolff F et al., 2018 [61]
28.4% Michalak SS, et al., 2018 [37]

The prevalence of UA varies from

5.8% to 43.7% of the cases.
 CLONAL HAEMOPOEISIS
 Changes & selective mutations occurring in HSC lineage.
 Prevalence of these mutations increase& accumulates with age
development of hematological malignancy
10-15% of UA were thought to belong to this

 Cytopenia lacking molecular aberrations and not fulfilling MDS criteria- called
Idiopathic Cytopenia of Unknown Significance (ICUS) - a pre MDS condition

 When present with anemia- ICUS-A

 Classical prototype of “anemia of old age”
 CLINICAL FEATURES
In elderly, anemia is ignored often
S/S of anemia occur as a result of reduced organ oxygenation

 Noticed that there are 75% chances of negligence of

symptoms

Also no related positive finding could be recognized on general

physical examinations- insufficient signs on physical
examination that are specific for mild to moderate anemia.
( Klara Gado et al 2022 )
GENERALIZED SYMPTOMS OF
ANEMIA

Fatigue,pale
skin, cold
extrimities
Tachycardia,
hypotension,
worsen
angina or
HFs
SOB, chest
pain,
headache,
syncope
B12 deficiency Iron deficiency Hair loss
SYMPTOMS OF ANEMIA-
Brittle nails
SPECIFIC CAUSE
Tachycardia

involvement(tumorous invasion)
Leucopenia-
infection

Bone marrow
Thrombocytopenia-
Bleeding
Glossitis
Pallor
Angular
stomatitis
Knuckle
pigmentation
 DIAGNOSTIC TESTS

BASIC ADVANCED DETAILED

• S. Ferritin • Serum/urin Hepcidin
• GENERAL BLOOD • Transferrin • STReceptor levels
PICTURE saturation • Bone marrow
• CBC • B12 & folate level • Tumor markers
• Retic count • LDH, Coomb’s • Molecular,
• SGOT/SGPT • USG cytogentic & flow
• Cr/ Albumin • Colonoscopy cytometry studies
• CRP • gastroduedonoscpy
• GFR
 PATTERNS IN DIFFERENT
STUDIES
Study Conclusion

Kim HS et al Normocytic normochromic (most

common)
Microcytic hypochromic (2nd most
common)
Macrocytic

Choi CW Normocytic (93.5%)

Microcytic (3.5%)
Macrocytic (3%)

Bhasin A et al Most common normocytic in 60-90

years age group
 GRADES OF ANEMIA
Most common grade - mild (57.1%) mild
to moderate anemia commonly affecting
females.

severe and life-threatening anemia is Mild

Grades of
anemia
confronted in males predominantly
Moderate
As greater part of the patients are mild
anemia only, findings are difficult to Severe
observe

pale conjunctiva usually noted when Hb

level drops below 9 gm/dl.
 Severity of anemia in patients
with unexplained anemia
n=981

Sylvia S et al (2019)

Moderate
anemia
(47.0%)
Mild Severe
Anemia Anemia
(47.4%) (5.6%)

Mild anemia: Pathiana

A (Study
• Men: 45% at old age
• Women: 24.8% home)
 Evaluation
& Management of
Anemia in Elderly
 MANAGEMENT OF ANEMIA
TREATMENT PLAN-
Multidisciplinary approach
Underlying cause of anemia-1* diagnosis
 Clinical condition-more frail the pt, more diff to tolerate
Any co morbidities / presence of symptoms
Out patient or admitted requiring surgery
Severity of anemia and indication of blood transfusion
Optimal age adjusted therapy to be started
Look for potential side effects
Look for impact on Quality of Life .
 IRON THERAPY
Oral iron supplements sufficient in IDA
New iron formulations, ferric maltol and Sucrosomial Iron–
higher efficacy and less side effects
(Gasche et al ) (Tarantino et al)

Not effective- reduced GI uptake, poor compliance, decreased

utilization due to inflammatory state, prolonged administration
IV Iron – valuable – in non adherent, unresponsive, intolerant

Newer formulations – safe and effective (ferric carboxymaltose

and iron isomaltoside)
ERYTHROPOIETIN TREATMENT
 Erythropoietin Stimulating agents (ESAs) like epoetin alfa and
darbepoetin alfa - anemia of CKD or CI or MDS

 Gowanlock et al (2017) studied effect of apoetin alfa in 570

patients of anemia >60yrs
Increase in Hb in 47% in UA
54% IN CKD

 Agnihotri et al (2007) studied beneficial effect of EPO on fatigue

and QOL in UA >65 yrs Females
significant increase in hemoglobin
improvement in QOL
 NOVEL THERAPIES
1-Hepcidin antagonists-(Fabiana Busti et al)
inhibition of hepcidin production (BMP6)
bind & antagonize hepcidin (Spiegelmer NOX-H94)

2-Hypoxia inducible factor(HIF)-physiological regulators of

transcriptional responses to hypoxia

3-Activin type 11receptor agonists (Luspatercept)-inhibit

negative regulators of late stage erythropoiesis- investigated in
anemia in elderly

4-Androgens- testosterone gel (Roy CN et al )

BLOOD TRANSFUSION THERAPY
More slowly with diuretics to
avoid TACO

Controversial in anemia
asymptomatics

 First line of treatment

Blood transfusion
Restrictive strategy ( Hb-7-
with severe anemia, 8gm/dl)- popular (Goodnough
LT et al , Murphy MF et al )
(Fabina et al 2019)

therapy
Not beneficial >10gm/dl
 s/s due to inadequate
tissue oxygenation
Guidelines agree to transfuse
<6-7gm/dl
 Hemodynamic
instability
More liberal transfusion in
CVD pts

(MINT trial, analysis from

Centre for Medicare Services)
Newer targeted drugs that may
counteract anemia in older
patients
 TAKE HOME MESSAGE
• Anemia in elderly is a global emergency, overlooked.

• It’s a challenge- as one or more etiology involved

• Grade and pattern of anemia should be confirmed

• Related to QOL , reduced functional capacity and increased mortality

• Target- improvement of QOL with specific treatment.

• Future research is essential for better diagnostic testing to look for the
etiology of geriatric anemia and evaluate effective therapies to reduce
the disease burden on the society.
s

THANK YOU