Haemolytic Anaemia Flashcards
Name the protein that is a specific indicator of haemolysis and outline how it is affected by haemolysis (2½) (CPATH)
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]
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)
Unconjugated bilirubin, haptoglobin, urine urobilinogen
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)
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
State whether the following will be increased, decreased or unchanged in urine in haemolysis. Explain answer (3) (CPATH)
Urobilinogen
Unconjugated bilirubin
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]
Classify the haemolytic anaemias and state one (1) example for each type (½x16 = 8) [Ess haem p60] (Super NB)
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
Classify the type of haemolytic anaemia caused by HS [1]
Intracorpuscular defect, a membrane disorder
Describe the underlying defect causing his disorder [2]
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)
List two (2) causes of spherocytes other than HS [1]
Autoimmune haemolytic anaemia, Clostridium perfringens infection, Burns, Incompatible blood transfusion, Haemolytic disease of newborn
Explain the use of the Coombs test in spherocytic haemolysis [1] & Describe the principle of this test [2]
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.
Name two (2) red cell enzyme deficiencies that may lead to chronic haemolytic anaemia (1)
G6PD & Pyruvate kinase
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)
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
This child is unlikely to have G6PD deficiency. Give the most important reason why this is unlikely (2)
It is inherited as an X-linked recessive condition, and therefore would be unusual in a female child.
Name the metabolic pathway affected in pyruvate kinase deficiency, and explain why the oxygen dissociation curve is shifted (3)
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.
A number of mechanisms exist to explain how drug-induced haemolysis occurs, name two (2)
Drug adsorption (hapten), Immune complex formation, Autoantibody production, Red cell membrane modification
List four (4) causes of fragmentation haemolysis (2)
DIC, TTP, HUS, Cardiac lesions, AV malformations, Malignant hypertension