1.4 Red cell disorders 1

Question 1

define anaemia

Answer 1

Reduction of Hb due to quantitative or qualitative impairment in red cell production

Question 2

What is the normal Hb in adult male and females?

Answer 2

Male: 135-180
Female: 115-160

Question 3

What are the clinical features of haemolytic anaemia?

Answer 3

Pallor
Jaundice
Splenomegaly
Gallstones (pigment from Hb)

Question 4

What are spherocytes?

Answer 4

red cells that are ball shaped instead of biconcave

Question 5

What are poikilocytes?

Answer 5

misshapen RBCs

Question 6

What is polychromasia?

Answer 6

fragmented RBCs

Question 7

What is reticulocytosis?

Answer 7

Increase in reticulocytes (immature RBCs)

Question 8

What is thalassaemia?

Answer 8

Imbalance in the globin chains of Hb

Question 9

What is haemoglobinopathy?

Answer 9

Structural abnormalities in globin molecule due to point mutations

Question 10

What is the normal Hb structure?

Answer 10

Tetramer of two alpha and two beta chains, each of which has a heme molecule to which an Fe is attached

Question 11

What is haemoglobin F?

Answer 11

Hb in foetus which has 2 alpha and 2 gamma chains (rather than beta like in adults HbA)

Question 12

What is haemaglobin A2?

Answer 12

2 alpha and 2 delta chains

Question 13

Which chromosomes encode the Hb genes and which ones encode which?

Answer 13

Chromosome 11: beta cluster, delta and 2 fetal gamma genes

Chromosom 16: alpha cluster

Question 14

How does Hb change from foetus to adult?

Answer 14

Hb F consists of alpha chains and gamma chains which predominate until the time of birth. After birth the gamma chains will be replaced by beta chains

Question 15

What tests can you use for Hb samples?

Answer 15

Alkaline gel electrophoresis
Acid gel electrophoresis
High performance liquid chromatography

Question 16

What are the clinical features of beta thalassaemia major?

Answer 16

Severe anaemia 
Ineffective erythropoiesis 
Extramedullary haemopoiesis 
Hair on end appearance on x-ray (skull)
Enlarged liver and spleen 
Expansion of flat bones of face and skull 
Spontaneous fractures 
Iron overload 
Reduced growth 
Endocrinopathy 
Delayed puberty

Question 17

What are the lab features of beta thalassaemia major?

Answer 17

hypo-chromic microcytic Anaemia
target cells, NRBCs
Marrow: red cell hyperplasia, increased iron
Most of Hb is HbF (A1 replaced by F)

Question 18

What is the treatment for beta thalassaemia major?

Answer 18

Long term transfusions
Iron chelation therapy (desferrioxamine SC or Deferasirox oral)
Allogenic marrow transplant
MRI imaging of liver and heart for iron content

Question 19

What is Beta thalassaemia intermedia?

Answer 19

Clinical syndrome which has traits of major but wil less severe clinical outcomes. Due to different genotypes such as HbE/B

Question 20

What causes beta thalassaemia minor?

Answer 20

Single gene defect

Question 21

What are the traits of beta thalassamia minor?

Answer 21

hypochromic, microcytic blood film with high RBC count

Raised HbA2 on electrophoresis

Usually picked up on routine tests - asymptomatic just have to think about it for genetic counselling

Question 22

What are the results of alpha thalassaemia?

Answer 22

4 genes: hydrops foetalis
3 genes: HbH disease, thalassaemia intermedia
1-2 genes: hypochromic, microcytic blood film and HbH bodies on incubation with dye

Question 23

What causes sickle cell anaemia?

Answer 23

Substitution of Valine for glutamic acid in the 6th position of the beta chain (single base change)

Question 24

How do you diagnose sickle cell anaemia?

Answer 24

Hb electrophoresis and DNA analysis

Question 25

What are the clinical features of sickle cell anaemia?

Answer 25

Pain due to vaso-occlusion (from adhesion) Infection: pneumonia, osteomyelitis, septic arthritis, parvovirus B19 Respiratory: acute chest syndrome, pulmonary hypertension CNS: stroke, haematuria Renal: haematuria, proliferative glomerulopathy, nephrotic syndrome, renal failure leg ulcers priapism

Question 26

What is hereditary spherocytosis?

Answer 26

a genetic defect in the proteins involved in the interaction between the membrane skeleton and phopholipid bilayer of the RBC memrane

Question 27

What is hereditary spherocytosis?

Answer 27

a genetic defect in the proteins involved in the interaction between the membrane skeleton and phopholipid bilayer of the RBC membrane abnormalities in the ankyrin and spectrin proteins

Question 28

What is the molecular defect in hereditary spherocytosis?

Answer 28

usually due to dominant mutations in ANK1 (ankyrin) or spectrin (SPTP)

Question 29

What are the clinical features of hereditary spherocytosis?

Answer 29

``` pallor jaundice splenomegaly gallstones leg ulcers aplastic crisis (will depend on age) ```

Question 30

What is used to diagnose hereditary spherocytosis?

Answer 30

Anaemia with spherocytosis Increased osmotic fragility positive cryohaemolysis test flow cytometery

Question 31

What is the treatment for hereditary spherocytosis?

Answer 31

often not required but can be splenectomy cholecystectomy for gallstones

Question 32

What is the pathophysiology of G-6PD deficiency?

Answer 32

Defective production of NADPH Lower levels of reduced glutathione (GSH) Oxidant stress Methaemoglobin forms (cant carry oxygen) Hb denatured RBC haemolysis

Question 33

What is the clinical presentation of G-6PD deficiency?

Answer 33

``` Chronic haemolytic anaemia Splenomegaly Neonatal jaundice Favism (precipitate haemolytic crisis) Primaquin sensitivity (malaria drug) Acute intravascular haemolysis due to drugs ```

Question 34

What will you see on a blood film with G-6PD deficiency?

Answer 34

Bite or blister cells - denatured Hb removed laving a pitted out pocket

Question 35

What drugs should G-6PD deficient people avoid?

Answer 35

Anti-malarial, anti-diabetic and antibiotics

Question 36

What happens in pyruvate kinase deficiency?

Answer 36

reduction in ATP in RBCs leading to the cells becoming rigid. This causes splenic trapping and a right shift in the Hb dissociation curve due to the build up of 2,3 BPG

Question 37

What are the clinical features or pyruvate kinase deficiency?

Answer 37

Haemolytic anaemia and jaundice in the newborn Splenomegaly Pigment gallstones

Question 38

What is the treatment of pyruvate kinase deficiency?

Answer 38

not needed in mild cases blood transfusion Splenectomy Potential for gene therapy