AnemiaAnemiaDr.Sana Delawer JalalDr.Sana Delawer Jalal

Lecturer /Sulaimani College of Medicine/ Dept.of Lecturer /Sulaimani College of Medicine/ Dept.of PathologyPathology

M.B.Ch.B, F.I.C.M.S.M.B.Ch.B, F.I.C.M.S.

Red Cell IndicesRed Cell Indices

Mean Cell Volume (MCV)Mean Cell Volume (MCV)► It is calculated from PCV and red cell count as follows:It is calculated from PCV and red cell count as follows:► MCV = PCV/RBC ( fl)MCV = PCV/RBC ( fl)

► Normal value:Normal value: 80-95 fl80-95 fl► It It decreasedecrease in iron deficiency anaemia and in iron deficiency anaemia and

haemoglopinopathieshaemoglopinopathies► It is It is increaseincrease in megaloblastic anaemia and chronic in megaloblastic anaemia and chronic

haemolytic anemia haemolytic anemia

Mean Cell Haemoglobin Concentration Mean Cell Haemoglobin Concentration (MCHC)(MCHC)

►It is calculated from the haemoglobin and PCV as It is calculated from the haemoglobin and PCV as follows:follows:

►MCHC = Hb/PCV g/dlMCHC = Hb/PCV g/dl

►Normal value:Normal value: 32-35.5 g/dl 32-35.5 g/dl►It is usually It is usually decreaseddecreased in iron deficiency anaemia in iron deficiency anaemia

(microcytic hypochromic anaemia)(microcytic hypochromic anaemia)

Mean Cell Haemoglobin Mean Cell Haemoglobin (MCH)(MCH)

► It is calculated from the haemoglobin and erythrocyte It is calculated from the haemoglobin and erythrocyte count as follows:count as follows:

► MCH = Hbx10/RBC pg MCH = Hbx10/RBC pg ► Normal value:Normal value: 27-32 pg 27-32 pg

► It is It is decrease decrease in iron deficiency anemia and in iron deficiency anemia and thalassaemia (microcytic hypochromic anemia)thalassaemia (microcytic hypochromic anemia)

► It is recognized by the pale colour of the red cell in the It is recognized by the pale colour of the red cell in the peripheral blood film peripheral blood film

► It is increase in macrocytic anemia (vitamin B 12 and It is increase in macrocytic anemia (vitamin B 12 and folic acid)folic acid)

Red Cell Distribution width Red Cell Distribution width (RDW)(RDW)

► RDW reflects the variation of RBCs volumeRDW reflects the variation of RBCs volume

it is usually performed by modern analysersit is usually performed by modern analysers

► Normal RDW varies between 12 to 17Normal RDW varies between 12 to 17

► Severe iron deficiency anemia is associated with Severe iron deficiency anemia is associated with increasedincreased RDW RDW

► Thalassemia and anemia of chronic disease are associated with Thalassemia and anemia of chronic disease are associated with normalnormal RDW RDW

DefinitionDefinition

AnemiaAnemia is a decrease in the number of RBCs, Hb content, is a decrease in the number of RBCs, Hb content, or Hematocrit below the lower limit of the normal range for or Hematocrit below the lower limit of the normal range for the age and sex of the individual the age and sex of the individual

► In adults, the lower extreme of the normal haemoglobin is In adults, the lower extreme of the normal haemoglobin is taken as 13.0 g/ dl for males and 11.5 g/dl for femaletaken as 13.0 g/ dl for males and 11.5 g/dl for female

► Newborn infants have higher haemoglobin level and, Newborn infants have higher haemoglobin level and, therefore, 15 g/dl is taken as the lower limit at birth therefore, 15 g/dl is taken as the lower limit at birth

Classification of AnemiaClassification of Anemia

►Several types of classifications of anemia's have Several types of classifications of anemia's have been proposedbeen proposed

►Two of the widely accepted classifications are Two of the widely accepted classifications are

based on :based on : ► The pathophysiology The pathophysiology

► The morphologyThe morphology

The Pathophysiological The Pathophysiological ClassificationClassification

Depending upon the Depending upon the pathophysiologic mechanism,pathophysiologic mechanism, anemias are anemias are

classified into 3 groups:classified into 3 groups: ►I. I. Anemia due to increased blood loss.Anemia due to increased blood loss.

► II. Anemias due to impaired red cell productII. Anemias due to impaired red cell production.ion.

► III. Anemias due to increased red cell destruction .III. Anemias due to increased red cell destruction .(Haemolytic )(Haemolytic )

The Morphological The Morphological ClassificationClassification

Based on:Based on:

1.1. Red cell size, Red cell size,

2.2. Haemoglobin content Haemoglobin content

3.3. Red cell indicesRed cell indices

Anaemias are classified into 3 types:Anaemias are classified into 3 types:► I. Microcytic, hypochromic I. Microcytic, hypochromic ► II. Normocytic, normochromic II. Normocytic, normochromic ► III. Macrocytic, normochromicIII. Macrocytic, normochromic

Simplified Classification Of Simplified Classification Of AnemiasAnemias

1. Deficiency anemias1. Deficiency anemias

2. Aplastic anemia2. Aplastic anemia

3. Hemolytic anemias3. Hemolytic anemias

4. Secondary anemias4. Secondary anemias

The Pathophysiological The Pathophysiological ClassificationClassification

Impaired Red Cell Impaired Red Cell ProductionProduction

A. A. Disturbance of proliferation and differentiation of stem Disturbance of proliferation and differentiation of stem cellscells ( aplastic anemia, pure red cell aplasia)( aplastic anemia, pure red cell aplasia)

B. B. Disturbance of proliferation and maturation of Disturbance of proliferation and maturation of erythrocytes:erythrocytes:

1.Defective DNA synthesis (megaloblastic anemias)1.Defective DNA synthesis (megaloblastic anemias)

2.Defective Hb synthesis:2.Defective Hb synthesis:a/. Deficient heme synthesis (iron deficiency)a/. Deficient heme synthesis (iron deficiency)b/. .Deficient globin synthesis (thalassemia)b/. .Deficient globin synthesis (thalassemia)

3. Unknown or multiple mechanisms (anemia of chronic disease, 3. Unknown or multiple mechanisms (anemia of chronic disease, anemia of marrow replacementanemia of marrow replacement))

Increased Rate Of Increased Rate Of Destruction Destruction

IntriIntrinnsic abnormalitiessic abnormalities HereditaryHereditary

1. 1. Red cell membrane dRed cell membrane defectsefects (Hereditary spherocytosis, (Hereditary spherocytosis, Hereditary Hereditary eliptocytosiseliptocytosis))

2. 2. Red cell enzyRed cell enzymme deficienciese deficiencies a/. Glycolytic enzymes: pyruvate kinase, hexokinasea/. Glycolytic enzymes: pyruvate kinase, hexokinase b/. Enzymes of hexose monophosphate shunt:b/. Enzymes of hexose monophosphate shunt: G-6PD, glutathione synthetase.G-6PD, glutathione synthetase.3. 3. Disorders of globin synthesisDisorders of globin synthesis a/. Deficient globin synthesis (thalassemia)a/. Deficient globin synthesis (thalassemia) b/. Structurally abnormal globin synthesisb/. Structurally abnormal globin synthesis (sickle cell anemia, unstable hemoglobins)(sickle cell anemia, unstable hemoglobins)

AcquiredAcquired1. Membrane defect: paroxysmal nocturnal 1. Membrane defect: paroxysmal nocturnal

hemoglobinuriahemoglobinuria

Increased DestructionIncreased DestructionExtriExtrinnsic Abnormalitiessic Abnormalities

1. 1. Antibody MediatedAntibody Mediated a/. Autoantibodies (idiopathic, drug-associated, a/. Autoantibodies (idiopathic, drug-associated,

SLE, malignancies)SLE, malignancies) b/. Alloantibodies (transfusion reactions, b/. Alloantibodies (transfusion reactions, erythroblastosis fetalis)erythroblastosis fetalis)

2. 2. Mechanical Trauma of RBCsMechanical Trauma of RBCs a/. Microangiopathic hemolytic anemias (thrombotica/. Microangiopathic hemolytic anemias (thrombotic thrombocytopenic purpura,hemolytic –uremic thrombocytopenic purpura,hemolytic –uremic

syndrome )syndrome ) b/. Cardiac traumatic hemolytic anemiab/. Cardiac traumatic hemolytic anemia3. 3. Chemicals and Micro organismsChemicals and Micro organisms

4. Sequestration in mononuclear phagocytic system4. Sequestration in mononuclear phagocytic system - hypersplenism- hypersplenism

Morphologic Classification Of Morphologic Classification Of AnemiasAnemias

TypeType MCVMCV MCHC MCHC Common Common causecause

________________________________________________________________________________________________________► Macrocytic anemiaMacrocytic anemia iincreased ncreased nnormal ormal Vitamin BVitamin B12 12 deficiencydeficiency

Folic acid deficiencyFolic acid deficiency

Microcytic anemiaMicrocytic anemia

- hypochromic- hypochromic ddecreased ecreased ddecreased ecreased Iron deficiency Iron deficiency ThalassemiaThalassemia

- normochromic- normochromic ddecreased ecreased nnormal ormal S Spherocytosispherocytosis or normalor normal

Normocytic anemiaNormocytic anemia nnormal ormal nnormal ormal Aplastic anemiaAplastic anemia- normochromic- normochromic Chronic renal failure Chronic renal failure

Some hemolytic Some hemolytic anemiaanemia

NormocyticMacrocytic

Microcytic

Anemia

Classification of anemias using MCV

Iron DeficiencyAnemia

Anemia of Chronic Disorder

Lead Poisoning

ThalassemiaSideroblastic

Anemia

Microcytic AnemiaMCV<80 fl

NormocyticAnemias80-95 fl

Stem cells defects/Reduced Erythropoiesis

Hemolytic Anemias

Intrinsic Extrinsic

Intrinsic DefectsExtrinsic Causes

Megaloblastic anemia

HypothyrodisimLiver Disease

Drugs

AlcoholismMyelodysplastic

syndrome

Macrocytic AnemiasMCV> 95 fl

Hypochromic MicrocyticHypochromic Microcytic

Normochromic NormocyticNormochromic Normocytic

Laboratory InvestigationLaboratory Investigation

►Anemia is not a diagnosis, but a sign of underlying disease

►The objective of the laboratory is to :

determine the type of anemia as an aid in discovering the cause

► Screening is usually done with the CBC or Screening is usually done with the CBC or ""complete blood countcomplete blood count"" ► Most laboratories now use automated, multiparameter instruments which will provide Most laboratories now use automated, multiparameter instruments which will provide

results for the following parametersresults for the following parameters::

► Hemoglobin Hemoglobin ► Hematocrit Hematocrit ► Red cell count Red cell count ► MCV , MCH ,MCHC MCV , MCH ,MCHC ► RDW RDW ► White cell and platelet countWhite cell and platelet count► Differentia WBC count.Differentia WBC count.l l

Laboratory Investigation-Laboratory Investigation-contcont..

Laboratory Investigation of Hemolytic Laboratory Investigation of Hemolytic anemiaanemia

► These are dividing into 4 groups:These are dividing into 4 groups:

I-Tests show increased red cell breakdownI-Tests show increased red cell breakdown

II- II- Tests show increased red cell productionTests show increased red cell production

III- III- Tests show damage to red cellsTests show damage to red cells

IV- Tests show shortened red cell life spanIV- Tests show shortened red cell life span

Tests Show Increased Red Cells Tests Show Increased Red Cells Breakdown Breakdown

► Serum bilirubin-unconjugated (indirect)bilirubin is Serum bilirubin-unconjugated (indirect)bilirubin is raisedraised

► Urine Urobilinogen is Urine Urobilinogen is raisedraised

► Faecal Stercobilinogen is Faecal Stercobilinogen is raisedraised

► Serum haptoglobin ( α globulin binding protein) is Serum haptoglobin ( α globulin binding protein) is reduced or reduced or absentabsent

► Plasma lactic acid dehydrogenase is Plasma lactic acid dehydrogenase is raisedraised

► Evidence of intravascular haemolysisEvidence of intravascular haemolysis in the form of in the form of haemoglobinaemia, haemoglobinuria, haemosiderinuriahaemoglobinaemia, haemoglobinuria, haemosiderinuria

Tests Show Increased Red Cells Tests Show Increased Red Cells ProductionProduction..

► Reticulocyte count reveals reticulocytosis which Reticulocyte count reveals reticulocytosis which indicate marrow erythroid hyperplasiaindicate marrow erythroid hyperplasia

► Routine blood film shows macrocytosis, Routine blood film shows macrocytosis, polychromasia, and normoblasts polychromasia, and normoblasts

► Bone marrow show erythroid hyperplasiaBone marrow show erythroid hyperplasia

► X ray of bones shows evidence of expansion of X ray of bones shows evidence of expansion of marrow spaces especially in tubular bones and skullmarrow spaces especially in tubular bones and skull

Tests Revealing Damages Tests Revealing Damages To RBCsTo RBCs

► Routine blood film shows a variety of abnormal Routine blood film shows a variety of abnormal morphological appearances of red cellsmorphological appearances of red cells

► Osmotic fragility is increasedOsmotic fragility is increased

► Autohaemolysis test Autohaemolysis test

► Coomb's antiglobulin testCoomb's antiglobulin test

► Electrophoresis for abnormal haemoglobinElectrophoresis for abnormal haemoglobin

► Estimation of HbA2 Estimation of HbA2

Tests Show Shortened Red Cell Life Tests Show Shortened Red Cell Life SpanSpan

►Tested by CrTested by Cr5151 labeling method normal RBC life labeling method normal RBC life span of 120 days is shortened to 20-40 days in span of 120 days is shortened to 20-40 days in moderate haemolysis and 5-20 days in severe moderate haemolysis and 5-20 days in severe haemolysishaemolysis

Special InvestigationsSpecial Investigations

►Biochemical TestsBiochemical Tests

biochemical tests are aimed to identifying: biochemical tests are aimed to identifying: 1-Depleted cofactors necessary for normal hematopoiesis (iron, 1-Depleted cofactors necessary for normal hematopoiesis (iron,

ferritin, folate, B12).ferritin, folate, B12).

2-Abnormally functioning enzyme (glucose-6-phosphate 2-Abnormally functioning enzyme (glucose-6-phosphate dehydrogenase, pyruvate kinase), or dehydrogenase, pyruvate kinase), or

3-Abnormal function of the immune system (the direct antiglobulin 3-Abnormal function of the immune system (the direct antiglobulin [Coombs'] test). [Coombs'] test).

Thank you