1.4 Red cell disorders 1 Flashcards Preview

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Flashcards in 1.4 Red cell disorders 1 Deck (38):
1

define anaemia

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

2

What is the normal Hb in adult male and females?

Male: 135-180
Female: 115-160

3

What are the clinical features of haemolytic anaemia?

Pallor
Jaundice
Splenomegaly
Gallstones (pigment from Hb)

4

What are spherocytes?

red cells that are ball shaped instead of biconcave

5

What are poikilocytes?

misshapen RBCs

6

What is polychromasia?

fragmented RBCs

7

What is reticulocytosis?

Increase in reticulocytes (immature RBCs)

8

What is thalassaemia?

Imbalance in the globin chains of Hb

9

What is haemoglobinopathy?

Structural abnormalities in globin molecule due to point mutations

10

What is the normal Hb structure?

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

11

What is haemoglobin F?

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

12

What is haemaglobin A2?

2 alpha and 2 delta chains

13

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

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

Chromosom 16: alpha cluster

14

How does Hb change from foetus to adult?

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

15

What tests can you use for Hb samples?

Alkaline gel electrophoresis
Acid gel electrophoresis
High performance liquid chromatography

16

What are the clinical features of beta thalassaemia major?

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

17

What are the lab features of beta thalassaemia major?

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

18

What is the treatment for beta thalassaemia major?

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

19

What is Beta thalassaemia intermedia?

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

20

What causes beta thalassaemia minor?

Single gene defect

21

What are the traits of beta thalassamia minor?

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

22

What are the results of alpha thalassaemia?

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

23

What causes sickle cell anaemia?

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

24

How do you diagnose sickle cell anaemia?

Hb electrophoresis and DNA analysis

25

What are the clinical features of sickle cell anaemia?

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

26

What is hereditary spherocytosis?

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

27

What is hereditary spherocytosis?

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

28

What is the molecular defect in hereditary spherocytosis?

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

29

What are the clinical features of hereditary spherocytosis?

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

30

What is used to diagnose hereditary spherocytosis?

Anaemia with spherocytosis
Increased osmotic fragility
positive cryohaemolysis test
flow cytometery

31

What is the treatment for hereditary spherocytosis?

often not required but can be splenectomy

cholecystectomy for gallstones

32

What is the pathophysiology of G-6PD deficiency?

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

33

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

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

34

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

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

35

What drugs should G-6PD deficient people avoid?

Anti-malarial, anti-diabetic and antibiotics

36

What happens in pyruvate kinase deficiency?

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

37

What are the clinical features or pyruvate kinase deficiency?

Haemolytic anaemia and jaundice in the newborn
Splenomegaly
Pigment gallstones

38

What is the treatment of pyruvate kinase deficiency?

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