haemoglobin

Question 1

define haemolytic anaemia

Answer 1

anaemia resulting from shortened survival of red cells in circulation

Question 2

what can haemolysis result from

Answer 2

intrinsic abnormality of red cells, or from extrinsic factors acting on normal or abnormal red cells

Question 3

classifications of haemolytic anaemia

Answer 3

intrinsic vs extrinsic; inherited vs acquired; intravascular vs extravascular (normally partly both)

Question 4

what can result in inherited haemolytic anaemia (3 things with examples)

Answer 4

abnormalities in cell membrane (e.g. hereditary spherocytosis), haemoglobin (e.g. sickle cell) or enzymes in red cell (e.g. pyruvate kinase or G6PD deficiency)

Question 5

what can result in acquired haemolytic anaemia, and what can this lead to with regard to inherited anaemia

Answer 5

extrinsic factors e.g. micro-organisms, chemicals or drugs, that damage red cells (e.g. membrane, whole cell, Hb); precipitation of episodic haemolysis in individuals with G6PD deficiency can exacerbate any inherited haemolysis

Question 6

when does intravascular haemolysis occur

Answer 6

if very acute damage to red cell

Question 7

when does extravascular haemolysis occur

Answer 7

when defective red cells are removed by spleen

Question 8

4 reasons when to suspect haemolytic anaemia

Answer 8

otherwise unexplained, which is normochromic and usually either normocytic or macrocytic; evidence of morphologically abnormal red cells; evidence of increased red cell breakdown (increased billirubin causing gallstones); evidence of increased bone marrow activity

Question 9

inherited haemolytic anaemia: example of condition causing membrane defect

Answer 9

hereditary spherocytosis (haemolytic anaemia or chronic compensated haemolysis)

Question 10

inherited haemolytic anaemia: example of condition causing Hb defect

Answer 10

sickle cell anaemia

Question 11

inherited haemolytic anaemia: example of condition causing glycolytic pathway defect

Answer 11

pyruvate kinase deficiency (very rare)

Question 12

inherited haemolytic anaemia: example of condition causing pentose shunt defect

Answer 12

G6PD deficiency

Question 13

acquired haemolytic anaemia: example of situation causing immune membrane defect

Answer 13

autoimmune haemolytic anaemia

Question 14

acquired haemolytic anaemia: example of situation causing mechanical whole red cell defect and production of fragments

Answer 14

microangiopathic haemolytic anaemia

Question 15

acquired haemolytic anaemia: example of situation causing oxidant whole red cell defect

Answer 15

drugs and chemicals

Question 16

acquired haemolytic anaemia: example of situation causing microbiological whole red cell defect

Answer 16

malaria

Question 17

hereditary spherocytosis: effect of membrane defect on spleen removal

Answer 17

enter circulation and lose membrane in spleen, so red cells become less flexible and are removed prematurely by spleen (extravascular haemoloysis)

Question 18

hereditary spherocytosis: effect of premature removal on bone marrow

Answer 18

increases output of red cells, leading to polychromasia and reticulocytosis

Question 19

hereditary spherocytosis: what does haemolysis lead to in the liver

Answer 19

increased bilirubin production, jaundice and gallstones

Question 20

hereditary spherocytosis test

Answer 20

spherocytes more prone to haemolyse when osmotic pressure is reduced

Question 21

hereditary spherocytosis treatment

Answer 21

splenectomy in severe cases, but not until 5-6 years old

Question 22

hereditary spherocytosis: why is a good diet important, and alternative

Answer 22

avoids secondary folic acid deficiency, or take one folic acid tablet daily

Question 23

glucose-6-phosphate dehydrogenase (G6PD) deficiency: G6PD use

Answer 23

used in pentose phosphate shunt which protects red cell from oxidant damage

Question 24

glucose-6-phosphate dehydrogenase (G6PD) deficiency: how are oxidants generated in blood stream

Answer 24

during infection, or may be exogenous

Question 25

glucose-6-phosphate dehydrogenase (G6PD) deficiency: what might extrinsic oxidants be to cause haemolysis, and what is Hb oxidised to

Answer 25

foodstuffs (e.g. broad beans), chemicals (e.g. naphthalene), drugs (e.g. dapsone, primaquine); oxidised to MetHb

Question 26

glucose-6-phosphate dehydrogenase (G6PD) deficiency: where is the gene and who is this therefore likely to affect

Answer 26

on X-chromosome so affected individuals are usually hemizygous males (but occasionally homozygous females)

Question 27

glucose-6-phosphate dehydrogenase (G6PD) deficiency: what type of haemolysis does it usually cause

Answer 27

intermittent, severe intravascular haemolysis due to infection or exposure to exogenous agent (oxidant)

Question 28

glucose-6-phosphate dehydrogenase (G6PD) deficiency: what are episodes of intravascular haemolysis associated with

Answer 28

appearance of considerable numbers of irregularly contracted cells

Question 29

glucose-6-phosphate dehydrogenase (G6PD) deficiency: test

Answer 29

Hb denatures and forms around inclusions (“Heinz bodies”), which can be detected

Question 30

glucose-6-phosphate dehydrogenase (G6PD) deficiency: fate of Heinz bodies

Answer 30

removed by spleen, leaving cell defect (bite cell) as Hb present in one section (hemighost cell), and this is removed

Question 31

glucose-6-phosphate dehydrogenase (G6PD) deficiency: treatment

Answer 31

if acute, sometimes requires blood transfusion (prevention therefore important); take off any oxidative drugs

Question 32

autoimmune haemolytic anaemia: cause

Answer 32

results from production of autoantibodies directed at red cell antigens; Ig (and possible complement components) bound to red cell membrane recognised by splenic macrophages, which remove parts of red cell membrane, leading to spherocytosis

Question 33

autoimmune haemolytic anaemia: characteristics of spherocytes and effect on spleen

Answer 33

less flexible than normal red cells, so combination of rigidity and recognition of antibody and complement by splenic macrophages leads to removal of cells from circulation

Question 34

autoimmune haemolytic anaemia: 3 methods of diagonsis

Answer 34

find spherocytes and increased reticulocyte count, detect Ig +/- complement on red cell surface, detect antibodies to red cell antigens or other autoantibodies in plasma; clinical history will show not hereditary spherocytosis as sudden onset

Question 35

autoimmune haemolytic anaemia: 2 types of treatment

Answer 35

use of corticosteroids and other immunosuppressive agents, splenectomy for severe cases

Question 36

microangiopathic haemolytic anaemia: 2 types of treatment

Answer 36

removal of cause e.g. treating severe hypertension/stopping causative drug; plasma exchange when caused by an antibody in plasma leading indirectly to fibrin deposition