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Clinical Pathology - SGUL (Sem 4) > Haemolytic Anaemias > Flashcards

Haemolytic Anaemias Flashcards

1
Q

Define what anaemia and haemolytic anaemia is.

A

ANAEMIA = reduced haemoglobin level for the age and gender of the individual

HAEMOLYTIC ANAEMIA = anaemia due to shortened RBC survival

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2
Q

What are some characteristics of the mature RBC?

A

METABOLIC PATHWAYS:

  • glycolytic pathway
  • hexose-monophosphate shunt

MEMBRANE:
concave disc

HAEMOGLOBIN:
carries oxygen

If something goes wrong with any of these components, it can lead to haemolytic anaemia.

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3
Q

Describe haemolysis.

A

It is shortened red cell survival (of around 30 - 80 days).

The bone marrow compensates with increased red blood cell production. This means that we have increased young cells in circulation = reticulocytosis +/- nucleated RBCs.

There are two kinds of haemolysis:
COMPENSATED HAEMOLYSIS: RBC production able to compensate for decreased RBC life span = normal Hb
INCOMPLETELY COMPENSATED HAEMOLYSIS: RBC production unable to keep up with decreased RBC life span = decreased Hb

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4
Q

What are some clinical findings of haemolytic anaemia?

A
  • jaundice
  • pallor/fatigue
  • splenomegaly
  • dark urine
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5
Q

What are some chronic findings of haemolytic anaemia?

A
  • gallstones - pigment
  • leg ulcers (NO scavenging)
  • folate deficiency
    (increased use)
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6
Q

What are some laboratory findings of haemolytic anaemia?

A
  • increased reticulocyte count
  • increased unconjugated bilirubin
  • increased LDH (lactate dehydrogenase)
  • low serum haptoglobin (a protein that binds free haemoglobin)
  • increased urobilinogen
  • increased urinary haemosiderin
  • abnormal blood film
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7
Q

What are some things you would see on the blood film of someone with haemolytic anaemia?

A
  • increased reticulocytes (supravital stain)
  • polychromasia
  • nucleated RBCs
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8
Q

What are the different classifications of haemolytic anaemia?

A

INHERITANCE:

  • Inherited: hereditary spherocytosis
  • Acquired: Paroxysmal nocturnal haemoglobinuria

SITE OF RBC DESTRUCTION:

  • Intravascular (inside vessels): Thrombotic thrombocytopenic purpura
  • Extravascular (outside of vessels): Autoimmune haemolysis

ORIGIN OF RBC DAMAGE:

  • Intrinsic: G6PD deficiency
  • Extrinsic: Delayed haemolytic transfusion reaction
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9
Q

Expand on the haemolytic anaemias classified as non-/inherited.

A

They can be congenital/inherited, such as:
MEMBRANE DISORDERS:
- spherocytosis
- elliptocytosis

ENZYME DISORDERS:

  • G6PD deficiency
  • pyruvate Kinase deficiency

HAEMOGLOBIN DISORDERS:

  • sickle Cell Anaemia
  • thalassaemias

They can also be acquired, due to:

  • immune factors
  • drugs
  • mechanical factors
  • microangiopathic
  • infections
  • burns

Examples would be such as Paroxysmal Nocturnal
Haemoglobinuria.

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10
Q

What does a normal red cell membrane consist of?

A
  • lipid bilayer
  • integral proteins
  • membrane skeleton
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11
Q

If the red cell has defects in its vertical interaction, what would it lead to and what proteins would be likely to be affected?

A

It could lead to hereditary spherocytosis, and the proteins affected could be:

  • Spectrin
  • Band 3
  • Protein 4.2
  • Ankyrin
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12
Q

If the red cell has defects in its horizontal interaction, what would it lead to and what proteins would be likely to be affected?

A

It could lead to hereditary elliptocytosis, and the proteins affected could be:

  • Protien 4.1
  • Glycophorin C
  • (Spectrin - HPP)
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13
Q

Describe hereditary spherocytosis.

A

It is a common hereditary haemolytic anaemia. It’s inherited in an autosomal dominant fashion (75%).

It occurs when there are defects in proteins involved in vertical interactions between the membrane skeleton and the lipid bilayer. This causes decreased membrane deformability.

The bone marrow makes a biconcave RBC, but as the membrane is lost, the RBC become spherical.

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14
Q

What are some clinical features of hereditary spherocytosis?

A
  • it’s asymptomatic to severe haemolysis
  • causes neonatal jaundice
  • jaundice, splenomegaly, pigment gallstones
  • reduced eosin-5-maleimide (EMA) binding (it binds to band 3)
  • there’s a positive family history
  • gives a negative direct antibody test
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15
Q

How would you manage hereditary spherocytosis?

A
  • you would have to monitor blood levels
  • give folic acid
  • give transfusions
  • may have to do a splenectomy
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16
Q

What is the role of the hexose monophosphate shunt?

A
  • it generates reduced glutathione

- it also protects the cell from oxidative stress

17
Q

What are some effects of oxidative stress on the cell?

A
  • oxidation of Hb by oxidant radicals
  • resulting denatured Hb aggregates & forms Heinz bodies – bind to membrane
  • oxidised membrane proteins – reduced RBC deformability
18
Q

Describe G6PD deficiency.

A

It is a hereditary, X-linked disorder. It’s common in African, Asian, Mediterranean and Middle Eastern populations.
It’s mild in African (type A), but more severe in Mediterraneans (type B).

The clinical features range from asymptomatic to acute episodes to chronic haemolysis.

19
Q

What can trigger the G6DP deficiency (by triggering oxidative stress)?

A
  • infections
  • fava/ broad beans
  • many drugs e.g.: Dapsone, Nitrofurantoin, Ciprofloxacin, Primaquine
20
Q

What are some features of a G6PD deficiency?

A
  • Haemolysis

On the blood film:

  • Bite cells
  • Blister cells & ghost cells
  • Heinz bodies (methylene blue)
  • Reduced G6PD activity on enzyme assay (may be falsely normal if reticulocytosis)
21
Q

Describe pyruvate kinase deficiency.

A

Pyruvate kinase is required to generate ATP.
It’s essential for membrane cation pumps (otherwise, deformability).

It’s an autosomal recessive disorder. On a blood film, due to the deformability of the membrane, you’ll see prickle cells.

It can become chronic anaemia, ranging from mild to transfusion-dependent. It improves with a splenectomy.

22
Q

What can go wrong with haemoglobin?

A

The problem can be QUANTITATIVE - thalassaemias:
- its production is increased/ decreased amount of a globin chain (though still structurally normal)

The problem can also be QUALITATIVE – variant haemoglobins:
- resulting in the production of a structurally abnormal globin chain

23
Q

Define thalassaemias.

A

There is imbalanced alpha and beta chain production.

The excess unpaired globin chains are unstable and precipitate and damage RBCs and their precursors.

This results in ineffective erythropoiesis in the bone marrow, and haemolytic anaemia.

24
Q

How would we diagnose thalassaemias?

A
  • asymptomatic
  • microcytic hypochromic anaemia
  • low Hb, MCV, MCH
  • increased RBC
  • often confused with Fe deficiency
  • HbA2 increased in b-thal trait –(diagnostic)
  • the a-thal trait is often diagnosed by exclusion
  • globin chain synthesis (rarely done now)
  • DNA studies (expensive)
25
Q

Describe some characteristics of beta thalassaemia major.

A

It is transfusion dependent in 1st year of life.

If not transfused:

  • failure to thrive
  • progressive hepatosplenomegaly
  • bone marrow expansion – leading to skeletal abnormalities
  • death in first 5 years of life from anaemia

Side effects of transfusion:

  • iron overload (as we can’t naturally excrete it)
  • endocrinopathies
  • heart failure
  • liver cirrhosis
26
Q

Briefly describe sickle cell disease (SCD).

A

There is a point mutation in the β globin gene, where glutamic acid is converted into valine.

This results in an insoluble haemoglobin tetramer when deoxygenated, resulting in Hb polymerisation.
This is how the sickle-shaped cells come about.

27
Q

What are some acute complications of SCD?

A
  • stroke: ischaemic and haemorrhagic
  • cholecystitis (gallbladder inflammation)
  • hepatic sequestration
  • dactylitis (digit inflammation)
  • bone pain & infarcts
  • osteomyelitis (bone infection)
  • retinal detachment
  • vitreous haemorrhage
  • chest syndrome
  • splenic sequestration
  • haematuria: papillary necrosis
  • priapism
  • aplastic crisis
  • leg ulcers
28
Q

What are some chronic complications of SCD?

A
  • silent infarcts
  • pulmonary hypertension
  • chronic lung disease, bronchiectasis
  • erectile dysfunction
  • azoospermia
  • chronic pain syndromes
  • delayed puberty
  • Moya-moya
  • retinopathy, visual loss
  • chronic renal failure
  • avascular necrosis
  • leg ulcers
29
Q

What are some clinical features of SCD?

A
  • painful crises
  • aplastic crises
  • infections
  • Acute sickling:
    Chest syndrome
    Splenic sequestration
    Stroke
  • Chronic sickling effects:
    Renal failure
    Avascular necrosis bone
30
Q

What are some laboratory features of SCD?

A
  • anaemia
  • Hb often 65-85
  • reticulocytosis
  • increased NRBC
  • raised bilirubin
  • low creatinine
31
Q

How would you confirm the diagnosis of SCA?

A

You could perform a solubility test where you expose the blood to a reducing agent.
If there is Hb S, it will precipitate out, giving up a positive result for the trait and disease.

We can also use an electrophoresis structure to separate out the Hb based on molecular weight.

32
Q

What are the two types of immune haemolysis?

A

There are two types, autoimmune and alloimmune.

33
Q

Describe autoimmune haemolysis.

A

It can be:

  • idiopathic (usually warm, IgG, IgM)
  • rug-mediated
  • cancer associated (LPDs)
34
Q

Describe alloimmune haemolysis.

A

It can be due to:

  • Transplacental transfer (haemolytic disease of the newborn: D, c, L) (ABO incompatability)
  • Transfusion related (acute haemolytic transfusion reaction, ABO) (delayed haemolytic transfusion reaction,
    e. g Rh groups, Duffy)
35
Q

Describe non-immune acquired haemolysis.

A

It could be paroxysmal nocturnal haemoglobinuria.

Or, it could be fragmentation haemolysis:

  • mechanical
  • microangiopathic haemolysis (disseminated intravascular coagulation, or thrombotic thrombocytopenic purpura)

Other:

  • severe burns
  • some infections: e.g. malaria

Clinical Pathology - SGUL (Sem 4) (62 decks)

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