Upload
afifi-faridz-xanedia
View
3.564
Download
0
Tags:
Embed Size (px)
DESCRIPTION
Classification of Anaemia
Citation preview
CLASSIFICATION OF ANAEMIA: NORMOCHROMIC NORMOCYTIC 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
• 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
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
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
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
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
Clinical Features
• Symptoms of anaemia• Splenomegaly• Jaundice• Megaloblastic crisis – folic acid deficiency due
to increase need
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
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
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
OxidantRBC Membrane damage
Hb Heinz bodies
GSH GSSG
NADP NADPH
G-6P 6PG
G6PD
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
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.
Differential Diagnosis
• Drug induced HA• Other enzymopathies eg Pyruvate kinase
deficiency• Haemoglobinopathies due to oxidative stress
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
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
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
Lab Diagnosis (Cont)
• BM- erythroid hyperplasia• Elevated Indirect & direct bilirubin • Solubility & sickling test• Hb Electrophoresis
TREATMENT1. BM transplantation2. Transfusion3. Hydroxyurea therapy
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
• Disorders include1) Thrombocytic thrombocytopenic purpurea
(TTP)2) Haemolyric uraemic syndrome (HUS)3) Disseminated intravascular coagulation (DIC)4) Haemolysis Elevated Liver enzymes & Low
Platelet (HELLP)