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Molecular Basis of Disease - SGUL (Sem 4) > Haemolytic Anaemias > Flashcards

Haemolytic Anaemias Flashcards

1
Q

Define Anaemia

A

reduced haemoglobin level for the age and gender of the individual

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2
Q

What is haemolytic anaemia?

A

anaemia due to shortened RBC survival

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3
Q

What is the normal RBC lifecycle

A
  • 2x1011 RBC/day in the bone marrow.
  • RBC circulate for approx. 120 days without nuclei or cytoplasmic organelles.
  • 300 miles travelled through microcirculation, as small as 3.5 microns.
  • Removal senescent RBC by RES
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4
Q

Describe the process of haemolysis

A
  • Shortened red cell survival to 30-80 days
  • Bone marrow compensates by increasing production
  • There are increased reticulocytes in circulation with or without nucleuses
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5
Q

What are the clinical findings in anaemia ?

A
  • Jaundice
  • Pallor
  • fatigue
  • Splenomegaly (enlarged spleen)
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6
Q

What are the chronic clinical findings

A
  • Gallstones - pigment stones
  • Leg ulcers - not healing due to lack of O₂ delivery
  • Folate deficiency - due to increased use
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7
Q

What are the lab investigations carried out for HA

A
  • Bone marrow findings
  • Peripheral blood film
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8
Q

What would be seen in a Bone marrow investigation in HA

A
  • Erythroid hyperplasia of BM, with normoblastic rxn, higher ratio of erythroid cells than myeloid cells
  • Reticulocytosis – variable
    Mild (2-10%) - Haemoglobinopathies
    Moderate to marked (10-60%) - IHAs, HS, G6PD-def.
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9
Q

what would be seen in a peripheral blood film in HA

A
  • Polychromatophilia, nucleated rbc, thrombocytosis; neutrophilia with left shift;
  • Morphologic abnormalities provides clue to underlying disorder: e.g. Sickled cells, Spherocytes, Target cells, Schistocytes (fragmented, triangular rbc) acanthocytes
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10
Q

What are some other findings of HA

A
  • Increased unconjugated bilirubin
  • Increased LDH (lactate dehydrogenase)
  • Decreased serum haptoglobin protein that binds free Hb
  • Increased urobilinogen
  • Increased urinary hemosiderin
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11
Q

How can Haemolytic anaemia’s be classified

A

Inheritance:

  • Hereditary
    Hereditary spherocytosis
  • Acquired
    Paroxysmal nocturnal haemoglobinuria

Origin of RBC damage:

  • Intrinsic (Intracorpuscular)
    G6PD-deficiency
  • Extrinsic (Extracorpuscular)
    Delayed Haemolytic Transfusion Rxn

Site of RBC destruction:

  • Intravascular
    Thrombotic Thrombocytopenic Purpura
  • Extravascular
    Autoimmune Haemolysis
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12
Q

What is the site of RBC destruction

A

Extravascular - Liver then excreted in faeces

Intravascular - Kidney then excreted in urine

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13
Q

What are the intrinsic causes of HA

A

Membrane defects:

  • Hereditary Spherocytosis (HS)
  • Hereditary Elliptocytosis (HE)
  • H. Pyropoikilocytosis

Enzyme defects:

  • G6PD
  • PK

Haemoglobin defects:

  • Sickle Cell Disease
  • Thalassaemia’s
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14
Q

What are the Immune-Mediated Extrinsic causes of HA

A

Autoimmune:

  • Warm
  • Cold
  • Drug induced

Alloimmune:

  • HDN
  • Haemolytic Transfusion
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15
Q

What are the Non-Immune-Mediated Extrinsic causes of HA

A

Red cell fragmentation syn:

  • Mechanical trauma
    e.g. artificial valve
  • Microangiopathic HA
    e.g. HUS, TTP, DIC

Drugs & chemicals

Infections:

  • Malaria, clostridium

March haemoglubinuria

Hypersplenism

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16
Q

What are the features of membrane disorders in HS

A
  • Asymptomatic to severe haemolysis
  • Neonatal jaundice
  • Jaundice, splenomegaly, pigment gallstones
  • *Reduced eosin-5-maleimide (EMA) binding – binds to band 3
  • Positive family history
  • Negative direct antibody test
17
Q

What are the Enzyme effects that cause HA

A
  • Defect in Glycolytic (Embden-Meyerhof) pathways
  • Defect in Glucose-6-phosphate dehydrogenase
18
Q

Explain how the defect works in the glycolytic pathway

A

RBC is unable produce ATP which is needed in powering Na/K pumps and needed in changing shape to fit though capillaries.
This way RBC can’t return to their original shape and lyse.

19
Q

Explain how the defect works in the G6PD shunt

A

G6PD is needed in the management of oxidants.
If not present in RBC oxidants can cause the RBC to lyse

20
Q

List all the globin disorders

A

Thalassaemia - quantitative:
defect in the rate of synthesis a globin chain (structurally normal)

SCD - variant haemoglobins: - qualitative
production of a structurally abnormal globin chain

21
Q

What causes thalassaemia disorders

A
  • Imbalanced alpha and beta chain production
  • Excess unpaired globin chains are unstable
  • Heterogenous gp genetic disorders.
  • Ineffective erythropoiesis
  • Clinically divided:
    Hydrop foetalis
    β-Thalassaemia major
    Thalassaemia intermedia
    Thalassaemia minor
22
Q

What are the clinical features of B-thalassaemia major

A
  • Severe anaemia
  • Progressive hepatosplenomegaly
  • Bone marrow expansion – facial bone abnormalities
  • Mild jaundice
  • Intermittent infections, pallor
  • Iron overload
23
Q

What does a peripheral blood sample show for B-thalassaemia major

A
  • Microcytic hypochromic with decreased MCV, MCH, MCHC
  • Anisopoikilocytosis; target cells, nucleated RBC, tear drop cells
  • Reticulocytes >2%
24
Q

What are some traits in B-thalassaemia minor

A
  • Asymptomatic
  • Often confused with Fe deficiency
  • α-thal trait often by exclusion
  • HbA2 increased in β-thal trait – (diagnostic)
25
Q

What are some Alpha (α)-thalassaemia disorders

A

Hb Barts hydrops syndrome (- -/- -):

  • deletion of all 4 globin genes
  • incompatible with life

HbH disease (- α/- -):

  • Deletion of 3/4 α-globin genes
  • Common in SE Asia
26
Q

What are the clinical features in Alpha Thalassaemia

A
  • Moderate chronic HA
  • Splenomegaly, hepatomegaly*
  • hypochromic microcytic, poikilocytosis, polychromasia, target cells
  • Electrophoresis - diagnostic

Thal. trait (minor) (- α/αα; - α/- α; - -/αα):
- Normal or mild HA
- MCV & MCH low

27
Q

What are the characteristics of Thalassaemia intermedia?

A

Disorder with clinical manifestation between major and minor; e.g. βE/mild β+ (HbE- β-thal)

  • transfusion independent
  • diverse clinical phenotype
  • Varying symptoms
  • Increased bilirubin level
  • diagnosis – largely clinical
28
Q

What is sickle cell disease?

A

SCD – refers to all diseases as a result of inherited HbS;

Hb S caused by single nucleotide substitution.
HbSS is sickle cell anaemia (homozygous state)
HbAS – sickle cell trait (heterozygous)

29
Q

What causes SCD

A
  • Point mutation in the β globin gene: e.g. glutamic acid at position 6 → valine (HbS)
  • Insoluble Hb tetramer when deoxygenated → polymerisation
  • “Sickle” shaped cells
30
Q

What are the clinical findings for SCD

A

Crises: Painful, Aplastic

Infections due to hyposplenism

Acute sickling:

  • Chest syndrome
  • Splenic sequestration
  • Stroke

Chronic sickling effects:

  • Renal failure
  • Avascular necrosis bone
31
Q

What are the Laboratory findings for SCD

A
  • Anaemia: Hb often 60-90
  • Reticulocytosis, Increased NRBC
  • Raised bilirubin, Low creatinine
32
Q

What is the solubility test for SCD

A
  • Expose blood to reducing agent
  • HbS precipitated
  • Positive in trait and disease

Molecular Basis of Disease - SGUL (Sem 4) (29 decks)

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