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A Practical Approach to Anemia. Dr.R.V.S.N.Sarma., M.D., M.Sc., (Canada) Consultant Physician & Chest Specialist Visit us at : www.drsarma.in. How to efficiently and accurately work up an anemic patient ?. Important to remember Anemia is a clinical sign of disease

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a practical approach to anemia

A Practical Approach to Anemia

Dr.R.V.S.N.Sarma., M.D., M.Sc., (Canada)

Consultant Physician & Chest Specialist

Visit us at : www.drsarma.in

How to efficiently and accurately work up an anemic patient ?

what is anemia
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 !

Will we ignore a fever with out investigation ?

Its diagnosis is not that simple !! We’ll make it

Its very common and imp. in our practice

Drug Rx. depends on the cause

What is Anemia ?

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definition of anemia
Decrease in the quantum of circulating red blood cell mass and there by ↓ O2 carrying capacity

Most common hematological disorder by far

Almost always a secondary disorder

As such, critical for all practitioners to know how to evaluate / determine its cause / treat

Definition of Anemia

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normal red cells
Normal Red Cells

No nucleus, enzyme packets

Biconcave discs – Haem + Gl

Center 1/3 pallor

Pink cytoplasm (Hb filled)

Cell size 7- 8 µ - capill. 2 µ

EM pathway, HMP

Negative charge – no phago

Na less, K more inside

100-120 days life span

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the factory bone marrow
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

Erythrod / Granulocyte Ratio 1:3

E:G ratio increases in Anemia

Large white areas are marrow fat

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hemoglobin hb
Hemoglobin (Hb)

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first question
The onset of Anemia

Acute versus chronic

Clues

Hemodynamic stability

Previous CBC

Overt blood loss

First Question

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screening tests anemia
Clinical Signs and symptoms of Anemia

Look for bleeding – all possible sites

Look for the causes for anemia

Routine Hemoglobin examination

Cut off marks for Hb –

US < 13.5 g WHO < 12.5 g

India (ICMR) Less than 12 g%

Screening Tests – Anemia

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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

Clinical Signs to be looked for

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pcv or hematocrit
57% Plasma

1% Buffy coat – WBC

42% Hct (PCV)

PCV or Hematocrit

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the three primary measures
Measurement Normal Range

RBC count (RCC) 5 million 4 to 5.7

Hemoglobin 15 g% 12 to 17

Hematocrit (PCV) 45 38 to 50

A x 3 = B x 3 = C - This is the rule of thumb

Check whether this holds good in a given result

If not -indicates micro or macrocytosis or hypochro.

The Three Primary Measures

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the three derived indicies
Measurement Normal Range

RCC 5 million 4 to 5.7

Hemoglobin 15 g% 12 to 17

Hematocrit 45 % 38 to 50

MCV C ÷ A x 10 = 90 fl

MCH B ÷ A x 10 = 30 pg

MCHC (%) B ÷ C x 100 = 33%

The Three Derived Indicies

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types of anemia
Types of Anemia

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causes of anemia
Decreased production of Red Cells

- Hypo proliferative, marrow failure

Increased destruction of Red Cells

- Hemolysis (decreased survival of RBC)

Loss of Red Cells due to bleeding

- Acute / chronic blood loss (hemorrhagic)

M = P x S ( L)

Causes of Anemia

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hypoproliferative anemias

Failure of cell maturation

Nuclear breakdown

Cytoplasmic breakdown

Folate or B12 deficiency

Globin defect

Haem defect

Sickle cell A

Defective DNA synthesis

Fe

Phorph

IDA, SA

Megaloblastic Anemia

Thalassemia

Hypoproliferative Anemias

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anemia second test
RETICULOCYTE COUNT %Anemia – Second Test
  • ‘RBC to be’ or Apprentice RBC
  • Fragments of nuclear material
  • RNA strands which stain blue

Normal

Less than 2%

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reticulocyte
Reticulocyte

No definite nucleus

Reticulum of RNA

Deep blue staining

Light blue cytoplasm

Cell size about 10 µ

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reticulocytes
Reticulocytes

Supravital

Leishman’s

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reticulocyte production index
For example, the RPI is calculated as follows

Reticulocyte count 9%

Hb content 7.5 g%

Correction for Anemia

= 9 x (7.5 ÷ 15) = 9 x 0.5 = 4.5 %

Correction for life span

4.5 ÷ 2 = 2.25 %

3. Thus, the RPI is 2.25

Reticulocyte Production Index

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anemia
Anemia

Hb% < 12, Hct < 38%

Hemolytic

Hypoproliferative

RPI < 2

RPI > 2

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workup third test
The next step is ‘What is the size of RBC’ ?

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 Anemia (lack of raw material)

Maturation defect with less production

Bone marrow suppression (primary/ secondary)

Workup – Third Test

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red cell size
Red Cell Size

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mean cell volume mcv
RBC size is measured indirectly by

The Mean Cell Volume (MCV) and RDW

MCV

Microcytic

Normocytic

Macrocytic

< 80 fl

80 -100 fl

> 100 fl

< 6.5 µ

6.5 - 9 µ

> 9 µ

Mean Cell Volume (MCV)

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anemia workup mcv

MCV

Microcytic

Normocytic

Macrocytic

Iron Deficiency (IDA)

Chronic Infections

Thalassemias

Hemoglobinopathies

Sideroblastic Anemia

Chronic diseases, CKD

Early IDA

Hemoglobinopathies

Primary marrow disorders

Combined deficiencies

Increased destruction

Megaloblastic anemias

Liver disease/alcohol

Hemoglobinopathies

Metabolic disorders

Marrow disorders

Increased destruction

Anemia Workup - MCV

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anemia workup 4 th test red cell distribution width rdw
Anemia Workup – 4th TestRed cell Distribution Width – RDW

RDW < 13

Mean 90 fl

RDW is 13

MCV 90 fl

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red cell distribution width rdw
Red cell Distribution Width - RDW

MCV

Microcytic

Normocytic

Macrocytic

Left

Mean 90

Right

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anemia workup 5 th 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 there any RBC inclusions ?

Are there any hemo-parasites in the RBC ?

Are leucocytes normal in number and D.C ?

Is platelet distribution adequate ?

Anemia Workup - 5th TestPeripheral Smear Study

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ida cbc
IDA -CBC

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severe hypochromia
Severe Hypochromia

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microcytic hypochromic anemia

Serum Ferritin

< 33 pmol / l

33-270 pmol / l

> 270pmol / l

TIBC (300-340)

N or ↓

HIGH

-

+

BM Fe

Not IDA, Other Mi A

Iron Deficiency Anemia IDA

Microcytic Hypochromic Anemia

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ida summary
Microcytic MCV < 80 fl, RBC < 6 µ

RDW Widened and shifted to left

Hypochromic MCH < 27 pg, MCHC < 30%

RPI < 2

Retic. count May be > 2 %

Serum ferritin Very low < 33 (p mols/L)

TIBC Increased > 340 (µg/dL)

BM Iron stain Iron is Absent

Response to Fe Rx. Excellent

IDA Summary

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ida some nuggets
Look for occult blood loss – 2 days non veg. free

Pica and Pagophagia – Ice sucking

Absorption of Haem Iron > Fe ++ > Fe+++

Food, Phytates, Ca, Phosphate, antacids ↓absorption

Ascorbic acid ↑absorption

Oral iron Rx. always is the best, ? Carbonyl Fe

FeSO4 is the best. Reserve parenteral Rx.

Packed cell transfusion in emergency

Continue Fe Rx at least 2 months after normal Hb

1 gram ↑in Hb every week can be expected

Always supplement protein for the Globin component

IDA- Some Nuggets

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microcytic anemias
Microcytic Anemias

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ringed sideroblasts in bm
Ringed Sideroblasts in BM

Prussian Blue Stain

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macrocytic anemias
A. Megaloblastic Macrocytic – B12 and Folate↓

B. Non Megaloblastic Macrocytic Anemias

Liver disease/alcohol

Hemoglobinopathies

Metabolic disorders, Hypothyroidism

Myelodystrophy, BM infiltration

Accelerated Erythropoesis -↑destruction

Drugs (cytotoxics, immuno suppressants, AZT, anticonvulsants)

Macrocytic Anemias

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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

Anemia - Macrocytic (MCV > 100)

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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

Macrocytosis of Alcoholism

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megaloblastic hematopoiesis
Marrow failure due to

Disrupted DNA synth. & ineffective erythropoesis

Giant precursors (Megaloblasts)

Nuclear : Cytoplasmic dyssynchrony in marrow

Neutrophil hyper segmentation & macro ovalocytes

Anemia (and often leukopenia & thrombocytopenia)

Almost always due to B12 or folate deficiency

Megaloblastic Hematopoiesis

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slide42
MBA

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macrocytosis mba
Macrocytosis -MBA

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hsn mba
HSN - MBA

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basophilic stippling mba
Basophilic Stippling - MBA

BS occurs in Lead poisoning also

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megalocyte in ps
Megalocyte in PS

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mba bm
MBA - BM

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mba bm1
MBA - BM

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pernicious anemia tongue
Pernicious Anemia - Tongue

Bald, smooth, lemon yellowish red tongue

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normocytic anemias
Chronic diseases, CKD

Early IDA

Hemoglobinopathies

Primary marrow disorders

Combined deficiencies

Increased destruction

Anemia of investigations -ICU

Normocytic Anemias

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anemia of chronic disease
Thyroid diseases

Malignancy

Collagen Vascular Disease

Rheumatoid Arthritis

SLE

Polymyositis

Polyarteritis Nodosa

Anemia of Chronic Disease
  • IBD
    • – Ulcerative Colitis
    • – Crohn’s Disease
  • Chronic Infections
  • – HIV, Osteomyelitis
  • – Tuberculosis
  • CKD, Renal Failure

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dimorphic anemia
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

‘Dimorphic’ Anemia

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slide55

Algorithm for Diagnosis of Anemia

Anemia Suspected

Thorough Clin, Bleed

Hb%, RCC, Hct Decreased

Ca, Leukemia, Ulcer

RPI, Retic count <2

RPI, Retic count >2

Identify the cause

MCV, MCH, MCHC, PSE

Hemolytic Anemia

Microcytic hypochromic

Macrocytic hypo/normo

Coombs DAT, IDAT

Iron Def. Anemia

Megaloblastic

Normoblastic

Hb electrophoresis

Ferritin, TIBC, BM Fe

Folate defici.

ALD, CLD, Drug

Osmotic fragility

Thalassemia, Hb pathy

B12 def., PA

Chr. Renal dis.

Acid hemolysis

Sederoblastic Anaem.

Hypothyroid

Cold agglutinins

Chr. Infection, Lead

BM infiltration

Coagulopathy, DIC

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anemia summary
If Hb% is low – Do not start on Iron straight away

Ask for RCC, Hematocrit – Derive MCV, MCH, MCHC

Order for Reticulocyte count – Is RPI < 2 % or > 2%

Thoroughly look for blood loss – acute / chronic / occult

Is it hypo-proliferative or hemolytic or hemorrhagic Anemia

If hypo proliferative – Microcytic or Macrocytic? (MCV, RDW)

If microcytic – IDA or others – Sr Ferritin TIBC, BM Iron

If macrocytic – Megaloblastic (B12, FA) or Normoblastic BM

If normocytic – Anemia of chr. Disease – Liver, CKD, Ca

Peripheral smear study for RBC size, shape, colouration etc.

If retic. count is ↑- HA work up; Hb EP, spl. tests

Anemia - Summary

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target cells
Target Cells
  • Liver Disease
  • Thalassemia
  • Hb D Disease
  • Post splenectomy

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tear drop cells
Tear Drop Cells
  • Myelofibosis
  • Infiltration of BM
  • Tumours of BM
  • Thalassemia

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drepanocytes ss
Drepanocytes - SS

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sickle cell anemia
Sickle Cell Anemia

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autosplenectomy ss
Autosplenectomy - SS

Normal spleen is 8 to 12 cm

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hemolytic anemia
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

Hemolytic Anemia

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tests used to diagnose hemolysis
Reticulocyte count

Combined with serial Hb

Hemoglobin electrophotesis

Serum LDH

Serum bilirubin

Haptoglobin

Urine hemosiderin

Hemoglobinuria

Tests Used to Diagnose Hemolysis

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tests to define the cause of hemolysis
Hemoglobin electrophoresis

Hemoglobin A2 (βeta-Thalassemia trait)

RBC enzymes (G6PD, PK, etc)

Direct & indirect antiglobulin tests (immune)

Cold agglutinins

Osmotic fragility (spherocytosis)

Acid hemolysis test (PNH)

Clotting profile (DIC)

Tests to define the cause of hemolysis

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slide77
MAHA

Micro Angiopathic Hemolytic Anemia

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slide78
MAHA

Micro Angiopathic Hemolytic Anemia

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spherocytosis
Spherocytosis

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spherocytosis1
Spherocytosis

Hereditary Spherocytosis

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spherocytosis2
Spherocytosis

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elliptocytes
Elliptocytes

Hereditary Elliptocytosis, B12 or Folate↓

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stomatocytes s lit like central pallor in rbc
StomatocytesSlit like central pallor in RBC
  • Liver Disease
  • Acute Alcoholism
  • H Stomatocyosis
  • Malignancies

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echinocytes evenly distributed spicules 10
EchinocytesEvenly distributed spicules > 10
  • Uremia
  • Peptic ulcer
  • Gastric Ca
  • PK-D
  • Called Burr Cells

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acanthocytes 5 8 spikes of varying length irregular intervals
Acanthocytes5-8 spikes of varying length, irregular intervals

Called Spur Cells, Occur in A H A

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shistocytes
Shistocytes

Fragmented, Helmet or triangle shaped RBC

  • MAHA
  • Prosthetic valves
  • Uremia
  • Malignant HT

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leukoplakia aplastic anemia
Leukoplakia - Aplastic Anemia
  • Chloramphenicol
  • Neomercazole
  • Sulfonamides
  • Analgin
  • Phenytoin
  • Butazolidin group
  • Anti Ca drugs

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normal bm high power
Normal BM High Power

E : G = 1 : 3

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shift in e g ratio
Shift in E : G Ratio

E : G = 2 : 1

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bm aplastic anemia
BM - Aplastic Anemia

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myelofibrosis
Myelofibrosis

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howell jolly bodies
Howell-Jolly Bodies

Absence of Splenic function; Nuclear chromatin in RBC

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pelger huet anomaly
Pelger-Huet Anomaly
  • Inherited condition
  • PMN - Spectacles
  • Heterozygous
  • Homozygous fatal
  • Neutrophil Bands ↑
  • Normal WCC
  • No e/o infection

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thank you all
Thank You ALL

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