HEMOLYTIC ANEMIA
DR. Subhan Ali R
HEMOLYTIC ANEMIA
• DEFINITION
• CAUSES
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• APPROACH TO DIAGNOSIS
• DIAGNOSIS
DEFINITION
• Anemia due to inability of the
bone marrow to compensate for
the degree of destruction of
RBC
Normal RBC destruction
• Life span 100- 120 days
• Towards the end red cell
surface changes make them
susceptible to phagocytosis by
RES
• Energy derived from glucose
breakdown maintains red cell
integrity
Hb metabolism
• Phagocytosed RBCS release Hb
• Broken down within RES
• Globin back to metabolic
protein pool
• Porphyrin ring of heam cleaved
by HO
• Yields biliverdin and CO
• Reduced to bilirubin
Haem degradation
Causes of hemolysis
• Extra vascular
• Intra vascular
Extra vascular
• 80-90% in Spleen
• Others sites are bone marrow
reticuloendothelial cells
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Characteristics
(1) ↑ Bilirubin - blood
(2) ↑ Stercobilinogen – stool
(3) ↑ Urobilinogen – urine
(4) ↑ Iron store – bone marrow
Intra vascular
• RBC destroyed while in circulation
• Minor pathway
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Characteristics
Haemoglobinemia
Haemoglobinuria
Haemosiderinuria
Serum haptoglobin
Causes
• Two types
• (A) Hereditary
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• (B) Acquired
Hereditary
• (A) Defect in RBC membrane
• (B) Defect in globins synthesis
• (C) Enzyme deficiency of glycolytic
pathway
• (D) Enzyme deficiency of pentose
phosphate pathway
• (E) Enzyme deficiency of RBC nucleotide
metabolism
Acquired
• (A) Immunohemolytic anemia
• (B) Fragmentation syndrome
• (C) Paroxysmal nocturnal haemoglobinuria
• (D) Drugs & chemicals
• (E) Thermal injury
• (F) Infections
Defect in RBC
membrane
• Hereditary spherocytosis
• Hereditary elliptocytosis
• Stomatocytosis
• Acanthocytosis
(Abetalipoproteinemia)
Defect in globins
synthesis
• Beta Thalassemias
• Alpha Thalassemias
• Sickling syndromes
• Unstable Hb disease
Enzyme deficiency of
glycolytic pathway
• Pyruvate kinase deficiency
• Hexokinase deficiency
Enzyme deficiency of
pentose phosphate
pathway
• Glucose-6-Phosphate
Dehydration deficiency (G-6-PD)
Enzyme deficiency of RBC
nucleotide metabolism
• Pyrimidine-5’-nucleotidase
deficiency
Immunohemolytic
anemia
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Autoimmune haemolytic anaemias
Due to warm antibodies
Idiopathic
Secondary
Due to cold antibodies
Cold agglutinin disease
Paroxysmal cold haemoglobinuria
Haemolytic disease of newborn
Fragmentation
syndrome
• Haemolytic uremic syndrome
• Thrombotic thrombocytopenic
purpura
• Disseminated intavascular
coagulation
• Prosthetic cardiac valves
Drugs & chemicals
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Drugs
Oxidant drugs
Primaquine
Dapson
• Chemicals
• Naphthalene
• Nitrites and
Nitrates
• Oxidizing
chemicals
Thermal injury
• Burn
• Electric shock
• Heat stroke
Infections
• Clostridium welchi septicemia
• Bartonellosis
• Cholera
APPROACH TO
DIAGNOSIS
• History
• Clinical Examination
• Laboratory Evaluation
History
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Complaints
Age at onset
Development of pallor
Duration of disease
Jaundice
Exposers to chemicals or drugs
Infection , fever
Color of urine
Color of stool
Family history
Clinical Examination
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Pallor
Jaundice
Gall stone
Spleenomegaly
Skeletal abnormalities
Leg ulcers
Laboratory Evaluation
• Peripheral blood examination
• Bone marrow examination
• Biochemical finding
• Specific test
Peripheral blood
examination
• RBC :-
POLYCHROMATOPHILIA
NUCLEATED RBC
RETICULOCYTOSIS
POIKILOCYTOSIS
SPHEROCYTE,
SICKEL CELL,
TARGET CELL,
SCHISTOCYTES,
ACANTHOCYTE
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WBC :-
NEUTROPHILIA
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PLATELETS :- ↑ GIANT
PLATELETS
Bone marrow
examination
 ERYTHROPOISIS – HYPERCELLULAR
REVERSE M:E RATIO – 1 : 1 to1 : 6 (NORMAL
3-7 : 1)
NORMOBLASTIC REACTION
PREPONDERANCE OF NORMOBLAST
DYSERYTHROPOISIS
(A) HOWEL JOLLY BODIES
(B) ABNORMAL HEMOGLOBNISATION
(C) IRREGULAR NUCLEAR BORDER
(D) ABNORMAL MITOSIS
• MYELOPOISIS – NORMAL
• MEGAKARYOPOISIS – NORMAL
Biochemical finding
• S. BILIRUBIN :- ↑
• URINE UROBILINOGEN :- ↑
• RATE OF BILIRUBIN PRODUCTION :- ↑
• S. LDH LEVELS :- ↑
• S. HAPTOGLOBIN :- ↓
• LIFE SPAN OF RBC :- ↓
Specific test
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Hemoglobinopathies
Fetal Hb estimation
Hb electrophoresis
Sickling test
Reticulocyte preparation
Cytochemical stain for HbF
Heinz body preparation
Specific test
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Spherocytosis
osmotic fragility
Acidified glycerol lysis test
Immune hemolytic
coomb test
Direct & indirect
Specific test
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G-6-PD deficiency
Methaemoglobin reduction test
Fluorescent spot test
Quantitative assay
Heinz body test
Ascorbate - cyanide test
Specific test
• P.K. deficiency
• Autohemolysis test
• Paroxysmal nocturnal
haemoglobinuria
• Ham’s acidified serum test
• CD 59, CD 55
Specific test
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Bite cell haemolytic anaemias :Heinz body test
Bite cell in PS
Methaemoglobinaemia
Spectroscopy
Paroxysmal cold haemoglobinuria
Landsteiner;s test