11- HAs: Specific Conditions

Question 1

what is hereditary spherocytosis? (type of HA?)

Answer 1

inherited, intrinsic membrane defect of RBCs causing haemolysis

Question 2

what happens during hereditary spherocytosis?

Answer 2

RBCs lose their biconcave shape and become spherical, removed from circulation and broken down faster

Question 3

clinical features of hereditary spherocytosis

Answer 3

vary from asymptomatic to severe haemolysis

• jaundice
• splenomegaly
• pigment gallstones

Question 4

list and describe the diagnostic tools for hereditary spherocytosis

Answer 4

reduced EMA binding to band 3 protein in RBC membrane

flow cytometry following EMA test for band 3 detection

positive family history

negative direct antibody test - differentiates between hereditary spherocytosis and autoimmune HA
= hereditary spherocytosis has a negative result - no autoimmune process causing RBC destruction, it’s primary a membrane disorder

Question 5

wat is pyruvate kinase deficiency (type of HA)?

Answer 5

intrinsic enzyme defect disorder

Question 6

what is the consequence of pyruvate kinase deficiency considering its importance?

Answer 6

significance - important glycolytic enzyme which provides energy to RBCs
- allows for deforming and reforming of RBCs to get through capillaries
- ATP needed for ionic balance of Na-K pump

consequence
- decreased ATP function = impaired RBC function and ionic balance = decreases lifespan = haemolysis leading to anaemia

Question 7

clinical presentation of pyruvate kinase deficiency

Answer 7

jaundice
splenomegaly
anaemia

Question 8

what is the consequence of G6PH deficiency considering its significance?

Answer 8

significance:
- important in pentose phosphatase pathway = G6PH catalyses the first-rate limiting step for producing NAPDH
- NAPDH is important for maintaining the reduced form of glutathione - helps protect RBCs against oxidative damage/stress

consequence:
- leads to NADPH and GSH impairment
- acute intravascular haemolysis

Question 9

what is G6PH?

Answer 9

glucose-6-phosphatase dehydrogenase

catalyses first rate limiting step in pentose phosphatase pathway - important for generating NADPH and glutathione = protects RBCs against oxidative damage and stress

Question 9

what is G6PH deficiency?

Answer 9

X-linked disorder/ inherited enzyme detect
- seen in the same ethnic groups as haemoglobinopathies

Question 10

clinical features of G6PH deficiency

Answer 10

formation of Heinz bodies - denatured Hb
dark urine from excessive haemolysis and urobilinogen production
bite and basket cells

Question 11

what is thalassaemia?

Answer 11

intrinsic haemoglobin defect - globin disorder characterised by a deficit in globin synthesis

causes an imbalance in production of aloha and beta globin chains

Question 12

what is alpha thalassaemia?

Answer 12

heterogenous group of genetic disorders affecting/ reducing alpha globin chain synthesis

Question 13

list and describe the three different levels of alpha globin thalassaemia - describe differing disease severity and symptoms?

Answer 13

Hb Barts hydrops syndrome - deletion of all 4 alpha globin genes, severe condition that’s incompatible with life

HbH disease - deletion of 3 out of 4 alpha globin genes
= moderate/chronic haemolytic anaemia
= hepatosplenomegaly
= hypochromic microcytic cells, poikilocytosis, polychromasia, target cells

thalassaemia minor - carriers with 1 or 2 alpha globin chain deletions
= normal to mild haemolytic anaemia
= low MCV and MCH

Question 14

what is hydrops fetalis?

Answer 14

severe form of alpha thalassaemia

foetus lacks alpha globin chains needed for foetal development = leads to a low chance of survival

Question 15

what is beta thalassaemia?

Answer 15

heterogenous group of genetic disorders affecting/ reducing beta globin chain synthesis

Question 16

describe the three types of beta thalassaemia

Answer 16

major, intermedia, minor

major = significant reduction in beta globin chain synthesis

intermedia = intermediate severity, milder symptoms
= increased bilirubin, has a diverse clinical phenotype with varying symptoms

minor = asymptomatic carrier status with a slight reduction in beta globin chain synthesis

Question 17

what is sickle cell disease?

Answer 17

a group of autosomal recessive inherited globin disorders

Question 17

cause of SCD?

Answer 17

single nucleotide mutation on position 6 of the beta-globin gene = from A to T, glutamic acid to valine

creates an insoluble Hb tetramer when deoxygenated - presence of HbS forms sickle shaped cells

Question 18

what is HbSS?

Answer 18

homozygous for SC, chronic haemolytic anaemia

causes organ damage from ischaemia

Question 19

what is HbS

Answer 19

sickle cell trait - heterozygous
asymptomatic to mild symptoms

Question 20

what is HbSC?

Answer 20

compound heterozygous for SCD

milder than HbSS, still involves chronic haemolytic anaemia

Question 21

what is HbS-beta thalassaemia?

Answer 21

compound heterozygous state with beta thalassaemia

severity varies depending on type of b-thal. mutation present

Question 22

general symptoms of SCD?

Answer 22

painful/aplastic crises, infections from hyposplenism, acute sickling

painful/aplastic crises = painful periods of decreased RBC production leading to a sudden drop in Hb levels

infections due to hyposplenism = reduced spleen function increases infection susceptibility

acute sickling - can lead to chest syndrome, or splenic sequestration (blood pools in spleen, increases size)

renal failure

Question 23

labatory findings for SCD?

Answer 23

anaemia
reticulocytosis
increased nucleated red blood cells and bilirubin
low creatinine - indicative of renal dysfunction

Question 24

confirmatory diagnosis test for SCD?

Answer 24

blood is exposed to a reducing agent, causing HbS to precipitate

positive in both sickle cell trait/HbS and disease/HbSS

Question 25

what is HbH disease? clinical features?

Answer 25

form of beta thalassaemia with the deletion of 3 out of 4 alpha globin genes

= moderate/chronic haemolytic anaemia
= hepatosplenomegaly
= hypochromic microcytic cells, poikilocytosis, polychromasia, target cells