Haemolytic anemia

Dr Dumitha Govindapala

MBBS, MD (Col), MRCP (London),FRCP

Normal Red cell destruction

Mean life span of a RBC is 120 days

Red cells are removed extravascularly by the macrophages at

the end of their life span

Mainly in the bone marrow, liver and spleen

Hb is breakdown into heam and globin

Haem is then breakdown into iron and bilirubin

Globin chains are breakdown into amino acid and reutilized

for protein synthesis
Haemolytic anemia

Definition

Anemias which results from an increases rate

of red cell destruction without evidence of
ineffective erythropoiesis

Because of the erthropoeitic hyperplasia,

hemolytic anemia may not be seen until the
red cell life span is less than 30 days.
Haemolytic anemia

There are two main sites of RBC destruction

in haemolytic anemia

1. Extravascular haemolysis

2. Intravascular haemolysis
Extravascular Haemolysis

Excessive removal of red cells by the reticuloendothelial system

RBC are phagocytize by the macrophages in the liver and

spleen

Causes include RBC membrane abnormalities such as

Bound immunoglobulins on surface

Physical abnormalities restricting RBC deformability that

prevent egress from spleen

Extravascular haemolysis is characterized by spherocytes

Intravascular Haemolysis

Free Hb is released into the circulation

Free Hb binds to haptoglobins in the circulation

After haptoglobin is saturated excess free Hb is filtered in the kidney

In the PCT, iron is removed and converted into ferritin and

haemosiderin

If the rate of haemolysis exceeds the re-absorptive capacity of the

PCT, free Hb enters urine

Methaemalbumin is also formed from the process of intravascular

haemolysis
Intravascular haemolysis
The main laboratory features of intravascular
hemolysis are

-Haemoglobinaemia and haemoglobinuria

-Haemosiderinuria

-Methhaemalbumineamia
Haemolytic anemia - Classification

Mainly classified into two groups

Hereditary haemolytic anemia

Acquired haemolytic anemia

Also classified according to the type of defect

Intracorpuscular defect - defect within the RBC

Extracorpuscular defect - defect outside the RBC

Haemolytic anemia - clinical
features

Symptoms of anemia

Mild fluctuating jaundice

Leg ulcers

Pigmented gallstones related symptoms

Splenomegaly
Haemolytic anemia - Laboratory
findings

Features of increased RBC break down

- Increased unconjugated bilirubin

- Increased urine urobilinogen

- Increased faecal stercobilinogen

- Absent serum haptoglobins

Haemolytic anemia - Laboratory
findings

Features of increased RBC production

- Reticulocytosis

- Bone marrow erythroid hyperplasia

Haemolytic anemia - Laboratory
findings

Morphological changes on RBC

Osmotic fragility
Hereditary haemolytic anemias

Membrane defects

-Hereditary spherocytosis

-Hereditary eliptocytosis

Metabolism defects

-G6PD deficiency

-Pyruvate kinase deficiency

Haemoglobin defects

-Thalassemia

-Sickle cell anemia

Hereditary spherocytosis

Due to a defect in the proteins of the red cell

Red cells become spherical as they circulate

trough the spleen and the rest of the RE
system

Ultimately they become unable to pass

through the splenic microcirculation where
they die prematurely.
Hereditary spherocytosis

Autosomal dominant

Anemia may present at any age

Jaundice is typically fluctuating

Splenomegaly occurs in most patients

Pigmented gallstones are frequent

Blood picture - Hereditary spherocytosis
Blood picture shows microspherocytes

Classic finding is increased osmotic fragility

Principal form of treatment is splenectomy

Hereditary Eliptocytosis

Clinical and laboratory features are similar to

hereditary spherocytosis except for blood
film

Usually clinically milder disorder

Occasional patients require splenectomy

Glucose - 6 - phosphate
dehydrogenase deficiency

G6PD is the only source of NADPH in the RBC

NADPH is required for the production of reduced glutathione

Glutathione deficiency renders the RBC susceptible to oxidant stress

Although G6PD is present in all cells the main syndrome which

occur is acute hemolytic anemia in response to oxidant stress

There are wide variety of normal genetic variants of enzyme G6PD

Worldwide over 400 million people are G6PD deficient

Glucose - 6 - phosphate
dehydrogenase deficiency

The inheritance is X lined, affecting males

and carried by females

The female heterozygous have an advantage

of resistance to falciparum malaria
Glucose - 6 - phosphate dehydrogenase
deficiency - clinical features

Clinical features are of rapidly developing intravascular

hemolysis precipitated by an oxidant stress

-Drugs - antimalarials, sulphonamide,

chloramphenicol, nitrofurantoin, analgesics

-Infectons

Anemia is self limiting due to formation of new RBC

G6PD deficient neonates are more prone to neonatal

jaundice
Glucose - 6 - phosphate
dehydrogenase deficiency - diagnosis

Blood film - contracted and fragmented cells

Bite cells and blister cells

Blood counts are normal in-between crises

G6PD level - can be falsely normal in the

phase of acute haemolysis due to higher
enzyme levels in young RBC
Glucose - 6 - phosphate
dehydrogenase deficiency - Treatment

Stop the offending drug

Treat the underlying infection

Maintain high urine out put

Blood transfusion depends on the severity

Pyruvate kinase deficiency
Inherited as autosomal recessive disorder

Red cells become rigid as a result of reduced ATP formation

Degree of anemia varies widely

Symptoms of anemia are relatively mild due to right shift of the

oxygen dissociation curve

Jaundice is usual

Gallstones are frequent

Frontal bossing may be present

Pyruvate kinase deficiency

Blood film - poikilocytosis and prickle cells

Increase auto-hemolysis ( osmotic fragility) ;

but not corrected by glucose in contrast to HS

Direct enzyme assay is needed for the

diagnosis

Splenectomy is done for patients who need

frequent transfusions
Genetic disorders of hemoglobin

Normal adult blood contains three types of

Hb
• Hb A - two alpha and two beta chains
• HbF - two alpha and two gamma chains
• HbA2 - two alpha and two delta chains
Genetic disorders of hemoglobin

The major switch of fetal Hb to adult Hb

occurs 3-6 months after birth

Hb abnormalities results from

-Synthesis of an abnormal haemoglobin

-Reduced rate of synthesis of normal globin

chains
Thalassaemia

Mainly two types

Alpha Thalassemia

Beta Thalassemia
Alpha Thalassemia syndromes

Usually caused by gene deletion

Clinical severity can be classified according to the number of genes that are missing
or inactive

Loss of all four genes

- result complete suppression of alpha chains synthesis - severe disease

- Alpha chain is essential for fetal as well as adult Hb

- Therefore this is incompatible with life and leads to death in utero

Loss of three genes

- Moderate to severe disease

- Anemia (Hb is 7-12g/dL ) with splenomegaly

Alpha Thalassemia syndromes

Loss of one to two genes (alpha thalassaemia trait)

- Usually not associated with anemia

- MCV and MCH is low

-Red cell count is over 5.5 x 1012 /L

- Hb electrophoresis is normal
Beta Thalassemia syndromes

This condition occurs on average in one in four

offspring, if both parents are carriers of beta
thalassemia trait

Either no beta chains or small amount of beta

chains

Unlike in alpha thalassemia majority of genetic

lesions are point mutations than gene deletions
Beta Thalassemia major - clinical
features

Severe anemia become apparent at 3-6 months after

birth, when the switch of gamma to beta chain
synthesis should take place

Hepato - splenomegaly

Expansion of bones caused by intense marrow

hyperplasia - thalasaemic facies
Beta Thalassemia major - clinical
features

Infections - due to many reasons

• Anemia - prone to bacterial infections
• Splenectomy - meningococcal,
pneumococcal and haemophilus
• Blood transfusions - hep C and B

Osteoporosis - in well transfused patients

Beta Thalassemia major - clinical
features
Iron overload due to recurrent transfusions

-Each 500ml of blood contains 250 mg iron

- Iron absorption from food is increased in these patients

- Iron damages the liver, endocrine organs (failure of growth,

delayed or absent puberty, diabetes mellitus, hypothyroidism)
and myocardium

- In the absence of iron chelation death occur in the seconds or

third decade due to congestive cardiac failure or cardiac
arrythmias
Beta Thalassemia major -
Laboratory features
Blood picture -Severe hypochromic microcytic anemia

Hb electrophoresis -Almost complete absence of HbA with all the

circulating Hb being HbF on High serum ferritin

Iron studies - iron overload - high serum ferritin, high serum iron
and transferrin saturation

Cardiac assesment - cardiomegaly, cardiac failure, arrhythmia

Liver function test - abnormal depend on the degree of liver

damage

Endocrine tests - depends on endocrine organ involvement

Beta Thalassemia major - treatment

Regular blood transfusions

• Target Hb > 10g/dL
• Usually requires 2-3 units every 4-6 weeks
• Fresh blood, filtered to remove WBC

Regular folic acid

Immunization against Hep B, C

Splenectomy with immunization for capsular organisms

Allogenic bone marrow transplant

Beta Thalassemia major - treatment

Iron chelation therapy

Used to treat iron overload

Dexferioxamine is orally inactive

Given as a subcutaneous infusion

Commenced after transfers ion of 10-15 units of blood

Iron chelated by dexferioxamine is mainly excreted in urine and 1/3

excreted in faces

Attempt to keep serum ferritin between 1000-15000µg/l

Deferiprone is an orally active second line iron chelator

Beta Thalassemia Intermedia

Moderately severe disease

Hb is 7-10g/dl

Do not need regular transfusions

Can be caused by various genetic defects

• Homozygous beta thalassemia with production of more HbF
• Mild defects in beta thalassemia chains
• Beta thalassemia trait with unusual severity
Beta Thalassemia Intermedia -
clinical features

Anemia

Jaundice

Patients may show bone deformities

Hepato- splenomegaly

Gallstones

Features of iron overload due to increased gut absorption ion of

iron
Beta Thalassemia trait (minor)

Common symptomless abnormality

Hypochromic microcytic anemia

Mild anemia (Hb > 10g/dL)

High RBC count > 5.5 x 1012/l

Raised HbA2

Serum ferritin, serum iron and TIBC normal

Severe than alpha Thalassemia

Beta Thalassemia trait (minor)

Co- existing iron deficiency should exclude when

evaluating these patients

Iron deficiency can result in falsely negative

HPLC ( High Performance Liquid
Chromatography) due to low HbA2 production

Family screening and genetic counseling is

important