Haemolytic Anaemia Flashcards

1
Q

Name the protein that is a specific indicator of haemolysis and outline how it is affected by haemolysis (2½) (CPATH)

A

Haptoglobin [½]. Haptoglobin binds free haemoglobin [1] and the haptoglobin-haemoglobin complex is cleared rapidly by the reticulo endothelial system, therefore lowering haptoglobin level in haemolysis [1]

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2
Q

List two (2) biochemical markers that would be useful to exclude in vitro (in tube) haemolysis (e.g. haemolysis occurring due to poor blood taking technique) (2x½ = 1) (CPATH)

A

Unconjugated bilirubin, haptoglobin, urine urobilinogen

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3
Q

List three (3) laboratory features (biochemical and peripheral blood smear) that may be found in active intravascular haemolysis/ confirm diagnosis of haemolytic anaemia. Explain why these finding occur in each example (3) (Super NB)

A

Coombs test: Confirm immune basis of haemolysis

Features of increased red cell breakdown
Decreased Haemoglobin due to red cell destruction
Increased Serum unconjugated bilirubin: Red cell destruction with Hb breakdown into heme & globin. Heme broken down to bilirubin.
Increased Serum Lactate dehydrogenase (LDH): Release of red cell isoenzyme by destroyed red cells
Decreased Serum haptoglobin: Binding of released Hb
Increased Urine urobilinogen
Increased Aspartate aminotransferase

Features of increased red cell production

Reticulocytosis (Reticulocyte count)/ polychromasia: Bone marrow/erythroid response to anaemia
Peripheral blood smear for Red Cell Morphology may show polychromasia or specific red cell abnormalities e.g.
Spherocytes (extravascular haemolysis due to IgG coating or hereditary membrane defect with splenic trapping)
o Fragments (microangiopathic or macrovascular red cell destruction)
o Bite cells (oxidative stress)
o Nucleated red blood cells (bone marrow stress)
o Sickle cell etc.
Red cell survival is shortened (measured by 51Cr labelling of the red cells)
Haemosiderinuria, Haemopexin, Methaemoglobin

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4
Q

State whether the following will be increased, decreased or unchanged in urine in haemolysis. Explain answer (3) (CPATH)

Urobilinogen

Unconjugated bilirubin

A

a. Urobilinogen. Increased [½] due to increased flux through the bilirubin pathway due to haemolysis [1]
b. Unconjugated bilirubin. Unchanged [½] because not water soluble [1]

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5
Q

Classify the haemolytic anaemias and state one (1) example for each type (½x16 = 8) [Ess haem p60] (Super NB)

A

Hereditary or Intracorpuscular defects
Membrane disorders - Hereditary spherocytosis (HS)
Haemoglobinopathies – Sickle cell (SCA)
Enzymopathies – G6PD

Acquired or Extracorpuscular defects
Immune – Allo, auto, drugs
Mechanical – Fragmentation syndromes
Infections – Malaria
Drugs – Dapsone
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6
Q

Classify the type of haemolytic anaemia caused by HS [1]

A

Intracorpuscular defect, a membrane disorder

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7
Q

Describe the underlying defect causing his disorder [2]

A

S is caused by defects in the vertical interactions between the red cell membrane skeleton and the lipid bilayer of the membrane. As a result, parts of lipid bilayer are lost and as a result the RBCs become spherical (loss of surface area relative to volume)

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8
Q

List two (2) causes of spherocytes other than HS [1]

A

Autoimmune haemolytic anaemia, Clostridium perfringens infection, Burns, Incompatible blood transfusion, Haemolytic disease of newborn

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9
Q

Explain the use of the Coombs test in spherocytic haemolysis [1] & Describe the principle of this test [2]

A

To distinguish AIHA from other causes of spherocytes. The Coombs reagent is an Ab or mixture of Abs which will react with Ig or complement which is adherent to the red cell. It will cause agglutination of red cells which have the relevant substance on their surface.

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10
Q

Name two (2) red cell enzyme deficiencies that may lead to chronic haemolytic anaemia (1)

A

G6PD & Pyruvate kinase

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11
Q

Explain the pathogenesis and pathophysiology of Glucose-6-phosphate dehydrogenase (G6PD) deficiency and name two (2) precipitating factors for acute haemolysis in this disease (7)

A

X-linked genetic disease. Enzyme malfunction/deficiency involved in pentose phosphate pathway causing decreased NADPH production. Unable to maintain reduced form of glutathione stores - inability to protect the cell against oxidative stress/ free radicals. Infection, Oxidant drugs, Fava beans

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12
Q

This child is unlikely to have G6PD deficiency. Give the most important reason why this is unlikely (2)

A

It is inherited as an X-linked recessive condition, and therefore would be unusual in a female child.

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13
Q

Name the metabolic pathway affected in pyruvate kinase deficiency, and explain why the oxygen dissociation curve is shifted (3)

A

Anaerobic glycolysis; there is an accumulation of 2,3-DPG and right shift of O2 dissociation curve, decreasing O2 affinity of Hb and anaemia better tolerated.

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14
Q

A number of mechanisms exist to explain how drug-induced haemolysis occurs, name two (2)

A

Drug adsorption (hapten), Immune complex formation, Autoantibody production, Red cell membrane modification

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15
Q

List four (4) causes of fragmentation haemolysis (2)

A

DIC, TTP, HUS, Cardiac lesions, AV malformations, Malignant hypertension

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16
Q

List two (2) examples of micro-angiopathic haemolytic anaemias (MAHA) (1)

A

TTP, HUS, DIC, vasculitis, disseminated malignancy, vasculitis, GPH

17
Q

Name two (2) causes of micro-angiopathic haemolytic anaemia (MAHA) (1)

A

DIC, Thrombotic thrombocytopenic purpura, Haemolytic uremic syndrome, Vasculitis, Malignant hypertension

18
Q

Name the test used to distinguish between immune and non-immune haemolytic anaemia and explain the test principles (3)

A

Coombs’ test: sensitised Ig/ complement coated RBCs agglutinate on addition of antihuman globulin (Coombs) reagent.

19
Q

Anaemia may be caused by haemophagocytic lymphohistiocytosis. State which cell type is hyperactivated in this condition (½) (IMMUNO)

A

Macrophages

20
Q

Outline the causes of this hyperactivation (3) (IMMUNO)

A

There is uncontrolled secretion of cytokines (e.g. IFNg, TNFa, IL-2, GM-CSF) from CD8+ T cells and natural killer cells because there is an underlying gene defect in perforin production. These cells cannot kill infected cells and there is an increase in systemic levels of pro-inflammatory cytokines and promotes excessive activation of macrophages.

21
Q

Briefly describe the sequence of events leading to Macrophage Activation Syndrome (2½) (IMMUNO)

A

When CD8+ T cells fail to clear infections, there is an increased secretion of systemic inflammatory cytokines, such as IFNg or TNFa (either), that causes activation of tissue resident macrophages.

22
Q

Name three (3) soluble factors that are involved in increased vascular permeability during secondary haemophagocytic lymphohistiocytosis (1½) (IMMUNO)

A

IL-1 (alpha or beta), TNFa and IL-6.

23
Q

Name two (2) familial conditions that leads to haemophagocytic disease (1) (IMMUNO)

A

Any of: Chediak-Higashi Syndrome, Griscelli syndrome, X-linked Lymphoproliferative syndrome or Wiskott-Aldrich syndrome

24
Q

Define AIHA and name the most important test that would confirm this diagnosis (2)

A

Autoimmune haemolytic anaemias are caused by antibody production by the body against its own red cells. Characterized by positive direct coombs test.

25
Q

Outline the mechanism whereby IgM coated red blood cells (RBCs) are destroyed in AMHA (2) (IMMUNO)

A

IgM/ antigen complexes (½) (IgM coated RBCs) are very effective at activating complement (½) and the ‘membrane attacked complex’ of complement (MAC) (½) destroys the RBCs by osmotic lysis (½)

26
Q

Outline the mechanisms whereby IgG coated RBCs are destroyed in AMHA (6x½ = 3) (IMMUNO)

A

IgG opsonization/ coating of RBC leads to phagocytosis (½) by macrophages (½) and intracellular lysis (½) of RBC. Macrophages have Fc receptors which bind to antibody (½).

Natural Killer (NK) cells (½) can also play a role in lysing antibody coated RBCs by the release of perforins (½)/ or by Antibody-dependent cell cytotoxicity.

27
Q

State which is clinically more severe, IgG or IgM mediated haemolytic anaemia, and explain why (4x½ = 2) (IMMUNO)

A

IgM is more dangerous (½). Much more rapid (½) and dangerous intravascular (½) hemolysis occurs as a result of complement activation. IgG coated RBCs are more gradually destroyed in spleen/ liver (½)

28
Q

Name a group of antigens which may be responsible for haemolytic disease of the newborn (½) (IMMUNO)

A

Rhesus group of Ag

29
Q

State where the antibodies that mediate haemolytic disease of the newborn come from (1) (IMMUNO)

A

Across the placenta (½), from the mother (½)

30
Q

Name the organ in a newborn infant where RBCs are destroyed as a result of AMHA (½) (IMMUNO)

A

Liver

31
Q

Explain how Rhesus haemolytic disease of the newborn develops (8)

A

Rh neg woman and Rh pos man conceive a child. Rh neg woman carries a Rh pos foetus. Cells from the foetus enter the woman’s blood stream. The woman becomes sensitized, antibodies form against Rh pos RBCs. With next pregnancy of a Rh pos foetus, maternal antibodies attack foetal RBCs

32
Q

Describe the pathogenesis of haemolytic disease of the newborn and list two (2) common blood group systems that evoke this response (½x9 = 4½)

A

Discrepancy in blood group between mother and baby, Feto-maternal bleed, Ab response in mother against blood group of baby, Second pregnancy (Ab response IgG), Cross placenta, Target red cells of baby, Haemolysis/ removal in spleen. ABO & Rh