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Anemia: Classification,general

features and approach

Definition of anemia
Anemia is functionally defined as an
insufficient RBC mass to adequately
deliver oxygen to peripheral tissues.

Indicators: Hemoglobin level,


hematocrit, RBC number

Adult Reference Ranges for Red Cells


Measurement (units) Men
Hemoglobin (gm/dL) 13.617.2
Hematocrit (%)
3949
Red cell count ( 106/L) 4.35.9
Reticulocyte count (%) 0.51.5
Mean cell volume (fL)
8296
MCH(pg)
2733
MCHC(gm/dL)
3337
RDW
11.514.5

Women
12.015.0
3343
3.55.0

Limitations in this concept


Hb and HCT may reflect altered plasma
volume not a change in RBC mass
Hb and HCT changes may reflect underlying
physiological conditions with different oxygen
needs

Classification
Etiological
Blood loss
Increased red cell destruction
Decreased red cell production (Hypo-proliferative
or maturation disorder)

Morphological

Clinical features
Symptoms depend on duration of the disease
Weakness
Fatigue
Palpitation
Shortness of breath
Tachycardia
Headache,vertigo,tinitus,parasthesias

Patient History

Dietary habits
Bowel habits
Medications
Exposure to chemicals and toxins
History of fever
Menstrual bleeding
Bruises,ecchymoses
Family history

Physical examination

Skin pallor/Pale conjunctiva


Jaundice
Smooth tongue
Sternal tenderness
Spleno/Hepatomegaly/lymphadenopathy
Purpura
Neurological dysfunction

Angular Stomatitis

Glossitis

Koilonychia

Laboratory Examination
First Line Studies
- CBC:Hb, Hcrit, Rbc indices, Cell count,

Reti count
- PB morphology examination
- Chemistry
-Urine examination

Second Line Studies


- Iron/TIBC/Ferritin
- BM study
-HPLC
- others

Useful RBC indices


Mean cell volume: the average volume of a red
cell expressed in femtoliters (fL)
Mean cell hemoglobin: the average content
(mass) of hemoglobin per red cell, expressed in
picograms
Mean cell hemoglobin concentration: the
average concentration of hemoglobin in a given
volume of packed red cells, expressed in grams
per deciliter
Red cell distribution width: the coefficient of
variation of red cell volume

Reticulocyte count

Corrected Reti(%)
(Reticulocyte Index, RI)

Correction of dilutional factor


= Reti(%) x Patients Hcrit / 45

Normal
Anemia

Red Cell Production Index(RPI)


Correction of shift factor
= Corrected Reti / Shift factor
BM normoblasts &
reticulocytes(days)

Hcrit

PB
reticulocytes(days)

45

3.5

1.0

35

3.0

1.5

25

2.5
1.5

2.0

15

2.5

Shift correction factor

Normal marrow response to anemia


Hematocrit

Production index

Marrow M/E ratio

45

3:1

35

2-3

2:1-1:1

25

3-5

1:1-1:2

15

3-5

1:1-1:2

Anemia alone or Not ?


Anemia alone
Bicytopenia or Pancytopenia
- Aplastic anemia/PNH
- MDS
- Acute leukemia
- Hypersplenism/Autoimmune disorders
- Megaloblastic anemia(not always)
- Myelophthisic anemia

Is there an appropriate reticulocyte


response to anemia
If reticulocytosis is present look for evidence
of hemolysis.
Hyperbilirubinemia
Increased LDH
Increased excretion hemoglobin (low
haptoglobin,hemoglobinemia,hemoglobinuria,he
mosiderinuria)

Anemia associated with low


reticulocyte count
Reflects impairment of normal hematopoeisis
Impaired erythropoeisis may be because of
Reduction in red cell precursors (hypogenerative)

Ineffective erythropoeisis

Macro-, Normo-, or Microcytic ?


Microcytic (MCV < 80 fL)
- IDA, Thalassemia, ACD

Macrocytic (MCV > 100 fL)


- Megaloblastic anemia, Reticulocytosis
Liver disease, Aplastic anemia

Normocytic
Anemia of renal failure, MDS, Leukemia, Aplastic
anemia, ACD, Others

R.INDEX<2.5

RBC MORPHOLOGY

N/N
MICRO OR MACRO

HYPOPROLIFERATIVE
MATURATION DISORDER

MARROW DAMAGE
CYOPLASMIC DEFECTS

INFILTRATION/FIBROSIS
IRON DEFICIENCY

APLASIA
THALESSEMIA

STIMULATION

RENAL DISEASE

METABOLIC DEFECTS
INFLAMMATION
MILD IRON DEFICIENCY

SIDEROBLASTIC ANEMIA
NUCLEAR DEFECTS
VIT B12/FOLATE DEFICIENCY
DRUG TOXICITY
REFRACTORY ANEMIA

R INDEX>2.5

HEMOLYSIS/HAEMORRHAGE
BLOOD LOSS
INTRAVASCULAR HEMOLYSIS
MEMBRANE ABNORMALITY
HEMOGLOBINOPATHY
AUTOIMMUNE DEFECT
FRAGMENTATION HEMOLYSIS
METABOLIC DEFECT

Is anemia associated with red cell populations


of different sizes?
Is the anemia associated with abnormalities
on peripheral smear?
Is a bone-marrow examination required for
clarifying the cause of anemia?

Peripheral Blood Smear

Size
Central pallour
Shape
Distribution
Inclusions
Abnormal cells

PBS Shape (cont)


Spherocyte,Sickle cell,schistocytes
Target cell increased ratio RBC
surface/volume
CLD, thalassemia

Teardrop
myelofibrosis

Acanthocyte (spur cells)


severe liver disease

Burr cell uremia, artifact

Microcytic hypochromic picture

Macrocytic picture

Megaloblasts in bone-marrow

Leuco-erythroblastic reaction

Normocytic picture with rouleaux

Spherocyte

http://www.wadsworth.org/chemheme/heme/microscope/spherocyte.htm

Sickle Cell

http://www.wadsworth.org/chemheme/heme/microscope/sicklecell.htm

Schistocyte

http://www.wadsworth.org/chemheme/heme/microscope/schistocyte.htm

Target Cell

http://www.wadsworth.org/chemheme/heme/microscope/targetcells.htm

Burr cell

http://www.wadsworth.org/chemheme/heme/microscope/echinocytes.htm

Tear drop cell (dacrocyte)

Rouleaux formation

http://www.wadsworth.org/chemheme/heme/microscope/rouleaux.htm

PBS - Inclusions
Nucleated RBC immature RBCs
Extramedullary hematopoiesis, hypoxia, hemolysis

Heinz bodies denatured and precipitated


hemoglobin
G6PD deficiency

Howell-Jolly bodies small nuclear remnant with the


colour of a pyknotic nucleus
s/p splenectomy, hyposplenism

Basophilic stippling deep blue granulations,


pathologic aggregation of ribosomes
Lead intoxication, thalassemia

Howell Jolly Bodies

http://www.wadsworth.org/chemheme/heme/microscope/howelljolly.htm

Basophilic stippling

http://www.wadsworth.org/chemheme/heme/microscope/basostip.htm

Bite cells and Heinz Bodies

When is bone-marrow required?


Refractory anemias
Parasites
Presence of abnormal cells on peripheral
smear
Rule out infiltration of marrow

Hypocellular bone marrow in aplastic


anemia

Contrast with erythroid hyperplasia

LD bodies in bone-marrow

Bone-marrow granuloma

Thank You..

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