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CLASSIFICATION OF ANAEMIA: NORMOCHROMIC NORMOCYTIC CHAPTER 3 Prepared by Noor Izzah Abd Rahman

Classification of anaemia

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Page 1: Classification of anaemia

CLASSIFICATION OF ANAEMIA: NORMOCHROMIC NORMOCYTIC

CHAPTER 3

Prepared by Noor Izzah Abd Rahman

Page 2: Classification of anaemia

Chapter outline

• Membrane defects: Hereditary spherocytosis• Metabolic defect: pyruvate kinase deficiency,

G6PD deficiency• Haemoglobinopathies: sickle cell disease• Extrinsic abnormalities: antibody mediated

transfusion reaction• Mechanical destruction: MAHA, infections

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• Underlying causes:1. Loss of RBC:Haemorrhage2. Increased destruction of RBC3. Reduced erythropoieisis4. Reduced RBC’s survival

Haemolytic anaemia can be classified into:5. Congenital and acquired6. Intrinsic or extrinsic7. Intravascular or extravascular haemolysis

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Morphologic classification of Anaemia – MCV based

Normocytic - MCV 80-100 fl

Intrinsic Extrinsic

N or h RETIC

Bone marrow

Acellular

Hypercellular

Normocellularh RETIC

PNH

Haeme/globin

Enzyme

Membrane

Haemolytic anaemia

Antibody mediated

InfectionChemical & Physical damage

Mechanical -MAHA

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Anaemia - Diagnostic Overview

Haemolysis

Review Blood Film

Morphology

None

PNH

Variable findings

Sickle cells

Stomatocytes

Elliptocytes

Target cells

Spur cells

Burr cells

Malaria

*Blister cells

Oxidative

G6PD

*Fragments

MAHA

Clinical Symptoms

Bilirubin hh Haptoglobin i

other biochem tests

Spherocytes

*DAT Positive

Immune mediated haemolysis

*DAT Negative

Hereditary Spherocytosis, Burns, C. perfringens septicaemia

Source; modified from AH Turner, 2004

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Hereditary Spherocytosis

• Characterized by numerous spherocytes in blood film

• Common in Northern European but can be found all over the world

• Due to deficiency of RBC membrane structural proteins leading to loss of membrane surface are----- causing the RBCs to become spherocytes

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Pathophysiology

• Defect in membrane skeletal proteins that connect the membrane skeleton to the lipid bilayer ( spectrin, ankyrin, protein 4.2, band 3)

• Cause RBCs progressively to lose unsupported lipid membrane because of the local disconnection

• RCs become rigid and their survival in the spleen decrease

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Clinical Features

• Symptoms of anaemia• Splenomegaly• Jaundice• Megaloblastic crisis – folic acid deficiency due

to increase need

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Lab Findings

• FBE- hallmark is d increase spherocytes• Hb normal, unless in crisis, MCV, MCH normal• Bone marrow- erythroid hyperplasia• Biochemistry – increased unconjugated bilirubin,

fecal urobilinogen and decreased haptoglobin• DAT test- negative• Osmotic frafility test – curve shift to left• Spectrin immunoassay• Family history and genetic studies

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Treatment & differential diagnosis

• Splenectomy – post splenectomy cause the appearance of target cells, howell jolly bodies, pappenheimer bodies

• Differential diagnosis – other causes of spherocytes must be ruled out AIHA, PNH,sepsis, pyropoikilocytosis

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Metabolic defect: G6PD Deficiency

• The gene for G6PD is located on X-chromosome & show a characteristic X-linked pattern

• Affect more males than females• G6PD fx – maintain gluthathione (GSSG) in

reduced state (GSH) to protect RBC from oxidative stress

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OxidantRBC Membrane damage

Hb Heinz bodies

GSH GSSG

NADP NADPH

G-6P 6PG

G6PD

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Clinical Features

• G6PD deficiency is usually asymptomatic but: 1.Acute haemolytic anaemia in response to oxidative stress such as drugs, fava beans, infections, etc.2.Neonatal jaundice3.Congenital non-spherocytic haemolytic anaemia

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Lab Findings

• FBE – depends on severity – normochromic normocytic, marked anisocytosis, poikilocytosis with bite cells and blister cells

• Biochemical - haptoglobin severely , unconjugated bilirubin and plasma Hb

• G6PD screening test – G6PD fluoresence spot test, G6PD enzyme detection kit, PCR analysis of mutations.

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Differential Diagnosis

• Drug induced HA• Other enzymopathies eg Pyruvate kinase

deficiency• Haemoglobinopathies due to oxidative stress

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Haem defects: Sickle Cell Disease

• Hb S is defined by structural formula α2β2Glu-val

which indictaes that on the B chain at 6th position, glutamic acid is replaced by valine

• resulting in a structural change in RBC shape relates to the amount of O2 bound to the Hb molecules

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Pathophysiology

• When HbS is fully oxygenated it remains soluble in the erythrocyte similar to Hb A, maintaining its normal shape

• On deoxygenation, Hb S becomes less soluble and causing sickling

• The blood becomes more viscous when sickle cells are created. Results in reduced blood flow which prolongs the exposure of HbS containing erythrocytes to a hypoxic environment which further promotes sickling,

• The end result is occlusion of capillaries and arterioles by sickled RBCs and infarction of surrounding tissues

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Clinical Features of SCD

• Hallmark feature is vaso occlusive• Gradual loss of splenic fx• Splenic sequestration

Laboratory diagnosis of SCD•Peripheral blood smear – poikilocytosis &anisocytosis, sickle cells, target cells, nRBCs, spherocytes, basohilic stippling, Howell-jolly bodies•Moderate leukocytosis & neutrophilia•thrombocytosis

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Lab Diagnosis (Cont)

• BM- erythroid hyperplasia• Elevated Indirect & direct bilirubin • Solubility & sickling test• Hb Electrophoresis

TREATMENT1. BM transplantation2. Transfusion3. Hydroxyurea therapy

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Microangiopathic Haemolytic Anaemia (MAHA)

• Due to mechanical destruction• It is a group of clinical disorders characterized by RBC

fragmentation in the circulation, resulting from IV haemolysis

• The fragmentation occurs as RBCs passed through fibrin deposits inside the lumen of arterioles & capillaries or through damaged epithelium & vessel walls

• RBCs being forced through a fibrin clot, attaching to fibrin, folding around the strands & fragmenting by the force of the flowing blood

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• Disorders include1) Thrombocytic thrombocytopenic purpurea

(TTP)2) Haemolyric uraemic syndrome (HUS)3) Disseminated intravascular coagulation (DIC)4) Haemolysis Elevated Liver enzymes & Low

Platelet (HELLP)

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