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 Women Hemoglobin (gm/dL) 13.617.2 12.015.0 Hematocrit (%) 3949 3343

Red cell count ( 106/L) 4.35.9 3.55.0 Reticulocyte count (%) 0.51.5

Mean cell volume (fL) 8296

MCH(pg) 2733

MCHC(gm/dL) 3337

RDW 11.514.5

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

Koilonychia Glossitis Angular Stomatitis

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

Hcrit 45

35

25

15

BM normoblasts & reticulocytes(days)

PB reticulocytes(days)

3.5

3.0

2.5

1.5

1.0

1.5

2.5

2.0

Shift correction factor

Normal marrow response to anemia

Hematocrit Production index Marrow M/E ratio

45 1 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,hemosiderinuria)

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

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..