Approach of Patients with Anemia

and
the Role of Erythropoietin
Djumhana Atmakusuma
Division HematologyMedical Oncology
Department of Internal Medicine
Faculty of Medicine, University of Indonesia

Approach of Patients with Anemia

(expert opinion in Jakarta)
What is
anemia ?

Is a patient anemic ?
Yes

Symptoms
and signs ?
Leukocyte ?
Platelet ?
Blood smear?
Overt
bleeding ?
Bleeding
in
women?

Male ?
Female ?

Hemolytic ?

Jaundice ?
Spleen enlarged?

Profuse ?
Needs
transfusion ?
Surgical ?

Gradually ?

Acutely ?

Hemodinamic
affected ?

Inherited ?
Aqcuired >

Occult
bleeding ?

No occult
bleeding ?

GIT
bleeding ?

Chronic
anemia ?

Morphology
of
erythrocyte ?

On diet ?

Diseases
cause
anemia ?

Anaemia:
Classification
Anemia ?
Haemoglobin
concentration below the
accepted normal range

Normal range for Hb:

affected by:
- sex
- age
- ethnics group
- altitude

Table 1.
Normal Haemoglobin Concentrations At
Different Ages
Age

Mean
haemoglobin
(g/L)

Lower limit
of normal
(g/L)

Birth (cord blood)

1 3 days (capillary)

165
185

135
145

1 month
2 6 months
6 months 2 years

140
115
120

100
95
105

2 6 years
6 12 years
12 18 years
Female
Male

125
135

115
115

140
145

120
130

Adult
Female
Male1

140
115
155
135
1Normal haemoglobin concentrations probably slightly
lower after 65 years.

Harrisons, Pronciples of Inernal Medicine, 16th ed 2004

Handbook of Transfusion - WHO

Severity of Anemia

Mild anemia

Hb: 9.5 13.0

Often no signs
or symptoms

Commonly remains
untreated

Moderate
anemia

Hb: 8.0 9.5

May present
with symptoms

Requires management to
prevent complications from
development

Severe
anemia

Hb: < 8

Symptoms
usually present

May be life threatening &

Requies promt management

Severity of anemia >< Symptoms

Mild anemia:
= patients may not
experience any
symptoms
= the symptoms may be
so mild that they are
not noticeable

As anemia becomes
more severe:
= symptoms can get
worse

If the anemia develops

rapidly patients may
notice the symptoms
right away

Symptoms and Signs of Anemia

tired, fatigued, weak

Some: = have a desire to eat ice or other

peculiar things
= experience sexual dysfunction
= have trouble concentrating
= performing mental tasks

dizzy, irritable
short of breath
depressed
pale skins
brittle nails
chest pain

a coldness in the hands or feet

Irregular heart beat
clinical features of anaemia are largely
caused by compensatory measures
mobilized to counteract hypoxia

Beside anemia ?
(anemia + leukocytosis or leukopenia)
What about Leukocyte ??
Leukocytosis
= myeloproliferative neoplasma (MPN)
- polycythemia vera
- myelofibrosis
= leukemia: acute or chronic ?
myeloid or lymphoid ?
Leukopenia
= hepatitis B, hepatitis C, HIV
= autoimmune disease: SLE or others
= medications (cytotoxics , others)
= bone marrow failure : aplastic anemia , MDS

Beside anemia ?
(anemia + thrombocytopenia leukopenia )
What about platelet ?
Thrombocytopenia ?
= leukemia: acute or chronic ?
myeloid or lymphoid ?
= hepatitis B, hepatitis C, HIV
= autoimmune disease: SLE or others
= medications (cytotoxics , others)
= bone marrow failure: aplastic anemia, MDS

Classifications of Anemia

Based on Causes
Etiology

Correlate

Based on Red Cell

Measurement
Red Cell
Morphology

Classification of Anaemia
Based on Causes

Abnormalities
in bone marrow

Abnormalities
in peripheral
blood & spleen

Classification of Anaemia
Based on Red Cell Measurement

Microcytic anemia

Macrocytic anemia

Iron deficiency anemia

Megalobastic anemia

Anemia of inflamation
(ACD)
Thalassemias
Sideroblastic anemias

Non megaloblastic
macrocytic anemia

Normocytic anemia
with normal or
depressed
reticulocytes
Anemia of chronic renal
failure
Anemia of chronic
diseases / inflamation
Anemia related to
intrinsic marrow diseases

Normocytic anemia
with elevated
reticulocytes
Anemia of acute blood
loss (post hemorrhagic
anemia)
Hemolytics anemia

Table 1. Causes of Iron Deficiency

Very common

Bleeding from the gastrointestinal tract (e.g. benign ulcer,

malignancy) in males and post menopausal women
Bleeding from the gastrointestinal tract , from menstruation
(menorrhagia methrorrhagia) in pre menopausal women
Bleeding due to myoma of the uterine in pre-/post-menopausal
women

Other

Pregnancy
Malabsorption (e.g. celiac disease, atrophic gastritis)
Malnutrition
Bleeding from urinary tract
Pulmonary haemosiderosis

Table 1. Classification of Thalassaemia

Type of Thalassaemia

Heterozygote

Homozygote

-Thalassaemia1
0 (--/)

Thal. minor

Hydrops fetalis

+ (--/)

Thal. minor

Thal. minor

Thal. minor

Thal. major

Thal. minor

Thal. major or intermedia

-Thalassaemia

1Compound

heterozygote (--/-) leads to HbH disease

Stress:
-Infections
-Pregnancy
- G6PD deficiency
consuming drugs

Hereditary anemia
(normal Hb/ mild
anemia ) eg in
thalassemia minor )

Overt moderate
Anemia

Table 1. Classification of the haemolytic anaemias

Inherited disorders
Red cell membrane

Hereditary spherocytosis and hereditary

elliptocytosis

Haemoglobin

Thalassaemia syndromes and sickling disorders

Metabolic pathways

Glucose-6-phosphate dehydrogenase and pyruvate

kinase deficiency

Acquired disorders

Immune

Warm and cold autoimmune haemolytic anaemia

Isoimmune

Rhesus or ABO incompatibility (e.g. haemolytic

disease of newborn, haemolytic transfusion reaction)

Non-immune and trauma

Valve prostheses, microangiopathy, infection, drug

or chemicals, hypersplenism

Table 1. Classification of the autoimmune haemolytic anaemias

Warm AIHA (usually IgG)
Primary (idiopathic)
Secondary

Lymphoproliferative disorders
Other neoplasms
Connective tissue disorders
Drugs
Infections

Cold AIHA (usually IgM)

Primary (cold haemagglutinin
disease)

Secondary

Lymphoproliferative disorders
Infections (e.g. mycoplasma)
Paroxysmal cold haemoglobinuria

Table 2.
Causes Of Microangiopathic Haemolytic Anaemia
Haemolytic uraemic syndrome (HUS)1
Thrombotic thrombocytopenic purpura (TTP)1
Carcinomatosis
Vasculitis
Severe infections
Pre-eclampsia
Glomerulonephritis
Malignant hypertension

1Some

authorities believe that HUS and TTP are effectively a single

disorder TTP-HUS

HUS versus TTP

Feature
Onset & course

HUS
age < 3 yr
males=females
recurrence: rare

Diagnosis

TRIAD:
ARF
Thrombocytopenia
Microangiopathy
anemia

TTP
peak: fourth decade;
neonatus90 y.o (35 y.o)
females > males (3:2)
recurrence: common
PENTAD:
CNS involvement
Thrombocytopenia
Microangiopathy
anemia
Renal involvevement
Fever

Tabel.1
Common Causes Of The Anaemia Of Chronic Disease

Malignancy
Rheumatoid arthritis
Various connective tissue disorders
Chronic infection
Extensive trauma

Women with anemia

Females:
= who want to be skinny low iron intakes in most
diets
= elite group of population
Menstruation:NormalMeno/methrorrahgia
- hormonal imbalance
- medications (eg. warfarin)
Pregnancy : - physiological anemia
- non overt underlying diseases
(e.g. SLE) pregnancy as a
trigger of anemia
Ectopic pregnancy: Pale, Abdominal Pain !!!

Anaemia >< Treatment &

Blood Transfusion
Wherever possible the cause of
anaemia should be determined before
the treatment is started
Blood transfusion is only required in a
minority of cases

A KEY of BLOOD TRANFUSION IN

ANEMIA
Blood loss:
- class III & IV:
mandatory
- class I & II:
order blood
Determining
Surgical Bleeding
!!!!

Chronic anemia
(Haemolytic anemia,
Malaria, HIV/AIDS,
G6PD deficiency, Bone
marrow suppression):
- If signs & symptoms of
inadequate oxygenation
of the tissue (+)
blood transfusion is
required

Prediction of Blood Loss based on Early Clinical Findings in

Male with Body weight of 70 Kg(2)
Parameters

Class I

Class II

Class III

Class IV

Blood loss (ml)

to 750

750 15000

1500 2000

> 2000

Blood loss
(% volume )

to 15 %

15 30 %

30 40 %

> 40 %

Pulse rate (minute)

< 100

>100

> 120

> 140

Blood pressure (mmHg)

normal

normal

decreased

decreased

Resp. rate (menit)

14 20

20 30

30 40

> 35

Urine prod. (ml/jam)

> 30

20 30

5 15

CNS/mental
status

restless mild

restless moderate

restless &
confused

Fluid replacement
(based on 3:1 rule)

cristaloid

cristaloid

cristaloid &
blood

Based on: The American College of Surgeon Committee on Trauma(2)

tidak ada
restless &
lethargic
cristaloid &
blood

Anaemia >< Treatment with

Exogen Erythropoietin
In anemia due to Chronic Kidney
Disease (CKD)
In anemia of chronic disorders :
cancer, rheumatoid arthritis, HIV / AIDS
In aplastic anemia and myelodsplastic
syndrome (MDS) in certain
conditions

Classifications of Anemia

Based on Causes
Etiology

Correlate

Based on Red Cell

Measurement
Red Cell
Morphology