A Practical

Approach to Anemia

How to efficiently and accurately

work up an anemic patient ?

Dr. Rizwan Aziz Qazi

Professor
G. Medicine PIMS.
 What is Anaemia ?

Important to remember
• Anemia is a clinical sign of disease
• It is not a single disease by itself
• Need to look for the underlying cause !
• Its diagnosis is not that simple !!
• Its very common and imp. in our practice
• Drug Rx. depends on the cause
 Anemia

• Decrease in the number of circulating red blood

cell mass and there by O2 carrying capacity
• Most common hematological disorder by far
• Almost always a secondary disorder
• Critical for all practitioners to know how to
evaluate / determine its cause / treat
Reticulocyte

No definite nucleus
Reticulum of RNA
Deep blue staining
Light blue cytoplasm
Normal Red Cells

No nucleus, Enzyme packets

Biconcave discs –
Center 1/3 pallor
Pink cytoplasm (Hb filled)
Negative charge – no phago
Na less, K more inside
100-120 days life span
The Factory – Bone Marrow

Sternum, pelvis, vertebrae, long

bones, skull bones, Tibia (paed)
From stem cells (pleuripotent)
75% of marrow for WBC
25% of BM for Red cells
Erythroid / Granulocyte Ratio 1:3
Large white areas are marrow fat
Hemoglobin (Hb)
 Approach to patient

History

• Physical Examination

• Investigations

• Treatment
 History

• Carefully obtain a history and perform a

physical examination in every patient with
anemia, because the findings usually provide
important clues to the etiology of the
underlying disorder.
 First Question

• The onset of Anaemia

• Acute versus chronic
• Clues
– Hemodynamic stability
– Previous CBC
 Blood loss Hx.

• Blood loss, carefully document pregnancies,

abortions, and menstrual loss. Estimates of
menstrual losses are notoriously inaccurate if
only routine inquiry is made.
• Often, patients do not appreciate the
significance of tarry stools.
 Dietary History

A thorough dietary history is important in a patient

who is anemic. This history must include foods
that the patient eats and those that he/she avoids,
as well as an estimate of their quantity.

Patients frequently attempt to deceive the physician

because of embarrassment regarding dietary
idiosyncrasies or financial restrictions.
 Relevant Hx.

• Obtain a history of fever because infections,

neoplasms, CVD can cause anemia and
occurrence of purpura, petechiae suggest the
occurrence of either thrombocytopenia or other
bleeding disorders;
• This may be an indication of more than 1 bone
marrow lineage is involved or that coagulopathy
is a cause of the anemia because of bleeding.
• Cold intolerance can be an important symptom
of hypothyroidism .

• The relation of dark urine to either physical

activity or time of day can be important in
march hemoglobinuria and paroxysmal
nocturnal hemoglobinuria
• Explore the presence or the absence of
symptoms suggesting an underlying disease,
such as cardiac, hepatic, and renal disease;
chronic infection; or malignancy.
 Family Hx.

• Family history not only for anemia but also for

jaundice, cholelithiasis (in males, at youg age),
splenectomy, bleeding disorders, and blood
transfusions. Carefully document the patient's
occupation, hobbies, prior medical treatment.
 Physical examination

• Too often, the physician rushes into the physical

examination without looking at the patient for an
unusual habitus or appearance of
underdevelopment, malnutrition, or chronic
illness.

• These findings can be important clues to the

underlying etiology of disease and provide very
helpful information .
• The skin,mucous membranes are often bypassed,
so that pallor, icterus, spider nevi, petechiae,
purpura, angiomas, ulcerations, palmar erythema,
coarseness of hair, puffiness of the face, thinning
of the lateral aspects of the eyebrows, nail defects,
are missed in the rush to examine the heart and
the lungs.
 Systemic examination

• Perform for palpable enlargement of lymph

nodes for evidence of infection or neoplasia.
Bilateral edema is useful in disclosing
underlying cardiac, renal, or hepatic disease,
whereas unilateral edema may suggest
lymphatic obstruction due to a malignancy that
cannot be observed or palpated.
• Search for hepatomegaly and splenomegaly.
• Patients with chronic disorders, these organs
are firm, nontender, and nonnodular.
• In patients with carcinoma, they may be hard
and nodular.
• The patient with an acute infection usually has
a palpably softer and more tender organ.
• N/L should include tests of position sense and
vibratory sense, examination of the cranial
nerves, and testing for tendon reflexes.
• Heart should not be ignored, enlargement
provide evidence of the duration and the
severity of the anemia, and murmurs :first
evidence of a bacterial endocarditis that could
explain the etiology of the anemia.
 Clinical Signs to be looked for

• Skin / mucosal pallor,

• Skin dryness, palmar creases
• Bald tongue, Glossitis
• Mouth ulcers, Rectal exam
• Jaundice, Purpura
• Lymph adenopathy
• Hepato-splenomegaly
• Breathlessness
• Tachycardia, CHF
• Bleeding, Occult Blood
 ANEMIA

ANEMIA
Decreased Production Increased Destruction
Anemia
• History and Exam
• Blood film
• MCV
• Reticulocyte count
• WBC, diff, platelets
 Screening Investigations

Routine Hemoglobin examination

• Cut off marks for Hb –
– US < 13.5 g WHO < 12.5 g
– Or decrease in >10 percent from baseline Hb.
 Causes of Anaemia

1. Decreased production of Red Cells

- Hypo proliferative, marrow failure
2. Increased destruction of Red Cells
- Hemolysis (decreased survival of RBC)
3. Loss of Red Cells due to bleeding
- Acute / chronic blood loss (hemorrhagic)
 Anaemia

Hb% < 12, Hct < 38%

Hypoproliferative Hemolytic

RPI < 2 RPI > 2

 Hypoproliferative Anaemias
Failure of cell
maturation
Nuclear Cytoplasmic
breakdown breakdown

Folate or B12 deficiency Haem defect Globin defect

Defective DNA synthesis Fe Phorph Sickle cell A

Megaloblastic Anaemia IDA, SA Thalassemia

 Anaemia – First Test

RETICULOCYTE COUNT %

• ‘RBC to be’ or Apprentice RBC

• Fragments of nuclear material
• RNA strands which stain blue
Normal
Less than 2%
 Normal CBC

www.drsarma.in
 Workup – Second Test
MCV …………...
MCV indicates the Red cell volume (size)
• Both the MCH & MCHC tell Hb content of RBC
• If the RPI is 2 or less
• We are dealing with either
– Hypoproliferative anaemia (lack of raw material)
– Maturation defect with less production
– Bone marrow suppression (primary/ secondary)
 Mean Cell Volume (MCV)

The Mean Cell Volume or MCV

MCV

Microcytic Normocytic Macrocytic

< 80 fl 80 -100 fl > 100 fl

 Anaemia Workup - MCV

MCV

Microcytic Normocytic Macrocytic

Iron Deficiency IDA Chronic disease Megaloblastic anemias
Chronic Infections Early IDA Liver disease/alcohol
Thalassemias Hemoglobinopathies Hemoglobinopathies
Hemoglobinopathies Primary marrow disorders Marrow disorders
Sideroblastic Anemia Combined deficiencies Increased destruction
Increased destruction
 Anaemia Workup – 3rd Test
Red cell Distribution Width – RDW

RDW < 13
RDW is 13
Mean
MCV90
90 fl

www.drsarma.in
 Red cell Distribution Width - RDW

MCV

Microcytic Normocytic Macrocytic

Left Mean 90 Right

 Anaemia Workup - 4th Test
Peripheral Smear Study
• Are all RBC of the same size ?
• Are all RBC of the same normal discoid shape ?
• How is the colour (Hb content) saturation ?
• Are all the RBC of same colour/ multi coloured ?
• Are intra RBC there any hemo-parasites ?
• Are leucocytes normal in number and D.C ?
• Is platelet distribution adequate ?
 IDA -CBC

www.drsarma.in
 Severe Hypochromia

www.drsarma.in
 Microcytic Hypochromic - IDA

www.drsarma.in
 Microcytic Anaemias

MCV < 80 fl Serum Iron TIBC BM Perls stain

Iron Def. Anemia ↓↓ ↑↑ 0
Chronic Infection ↓↓ ↓↓ ++
Thalassemia ↑↑ N ++++
Hemoglobinopathy N N ++
Lead poisoning N N ++
Sideroblastic ↑↑ N ++++
 Lab Test for DDx of Common Microcytic Hypochromic Anemias

Iron Thalassemia Chronic

Deficiency Minor Disease

Scrum Iron  N or  

TIBC  N or  N or 

% Iron  (< 10%) N or  

Saturation
Serum Feritin   
 Macrocytic Anaemias

A. Megaloblastic Macrocytic – B12 and Folate↓

B. Non Megaloblastic Macrocytic Anaemias
1. Liver disease/alcohol
2. Hemoglobinopathies
3. Metabolic disorders, Hypothyroidism
4. Myelodystrophy, BM infiltration
5. Accelerated Erythropoesis -↑destruction
6. Drugs (cytotoxics, immunosuppressants,
AZT, anticonvulsants)
 Megaloblastic Anemia - Drugs

• Folate antagonists • Nitrous oxide

 methotrexate • Arsenic
 trimethoprim • Chlordane
• Most cancer • Anticonvulsants
chemotherapy
 Dilantin
• Anti-retroviral
 Valproate
agents
 Lamotrigine
 zidovudine
 delavirdine
 lamivudine
 zalcitabine
Anemia - Macrocytic (MCV > 100)

Premature gray hair – consider MBA

Macrocytic anemias may be asymptomatic until
the Hb is as low as 6 grams
MCV 100-110 fl
must look for other causes of macrocytosis
MCV > 110 fl
almost always folate or B12 deficiency
 Macrocytosis of Alcoholism

• 25-96% of alcoholics
• MCV elevation usually slight (100-110 fl)
• Minimal or no anemia
• Macrocytes round (not oval)
• Neutrophil hyper segmentation absent
• Folate stores normal
Smoking increases the Red Cell Mass
 MCV > 115 fl DDX Folate or B12 Deficiency

Folic Acid B12 Deficiency

Deficiency
Peripheral smear & BM Same Same
morphology
Dietary Cause Common, in 3- Rare, except pure
4 months vegans, 3-4 yrs
Drugs interfering with Dilantin, oral Omeprazole
absorbtion contraceptives (Prilosec)
Neurologic findings No May be present

Methylmalonic acid level Normal Elevated

Schilling test Useful for

etiology
Obtain after Rx
 MBA

www.drsarma.in
 Macrocytosis -MBA

www.drsarma.in
 Pernicious Anaemia - Tongue

Bald, smooth, lemon

yellowish red tongue

www.drsarma.in
 Normocytic Anaemias

1. Chronic disease
2. Early IDA
3. Hemoglobinopathies
4. Primary marrow disorders
5. Combined deficiencies
6. Increased destruction
7. Anaemia of investigations -ICU
 Anaemia of Chronic Disease

• Thyroid diseases • IBD

• Malignancy – Ulcerative Colitis
• Collagen Vascular Disease – Crohn’s Disease
– Rheumatoid Arthritis • Chronic Infections
– SLE – HIV, Osteomyelitis
– Polymyositis – Tuberculosis
– Polyarteritis Nodosa • Renal Failure
 ‘Dimorphic’ Anaemia

• Folate & Fe deficiency (pregnancy, alcoholism)

• B12 & Fe deficiency (PA with atrophic gastritis)
• Thalassemia minor & B12 or folate deficiency
• Fe deficiency & hemolysis (prosthetic valve)
• Folate deficiency & hemolysis (Hb SS disease)
• Peripheral smear exam is critical to assess these
• RDW is increased very much
RBC Size – Anisocytosis
Different sizes of RBC
 Hemolytic Anaemia

Anemia of increased RBC destruction

– Normochromic, normocytic anemia
– Shortened RBC survival
– Reticulocytosis – due to ↑ RBC destruction
Will not be symptomatic until the RBC life span is
reduced to 20 days – BM compensates 6 times
 Tests Used to Diagnose Hemolysis

1. Reticulocyte count
2. Combined with serial Hb
3. Serum LDH
4. Serum bilirubin
5. Haptoglobin
6. Urine hemosiderin
7. Urobilinogen
 Findings in Hemolytic Anaemia

Reticulocyte count and RPI Increased

Serum Unconjugated Bilirubin Increased
Serum LDH 1: LDH 2 Increased
Serum Haptoglobin Decreased
Urine Hemoglobin Present
Urine Hemosiderin Present
Urine Urobilinogen Increased

.in
 Tests to define
the cause of hemolysis
1. Hemoglobin electrophoresis
2. Hemoglobin A2 (βeta-Thalassemia trait)
3. RBC enzymes (G6PD, PK, etc)
4. Direct & indirect antiglobulin tests (immune)
5. Cold agglutinins
6. Osmotic fragility (spherocytosis)
7. Acid hemolysis test (PNH)
8. Clotting profile (DIC)
 MAHA
Micro Angiopathic Hemolytic Anaemia
Spherocytosis
 Acanthocytes
5-8 spikes of varying length, irregular intervals
Called Spur Cells, Occur in A H A
 Pernicious anemia
Aplastic anemia

Myelodysplasia
Hemolysis
Normal
inflammation

Thal trait
Iron deficiency
50 70 90 110 130
MCV
Thank You ALL