Haemoglobinopathies and obstetric haematology

Question 1

What is RBC production controlled by?

Answer 1

EPO produced in the kidney

Question 2

What is Hb comprised of?

Answer 2

Central harm group

2 alpha and 2 non-alpha chains (beta, delta, gamma)

Question 3

Name the different types of Hb in a normal adult.

Answer 3

Hb-A - 2 alpha/2 beta
Hb-A2 2 alpha/2 delta
Hb- fetes - 2 alpha/2 gamma

Question 4

What are the two ways in which haemoglobinopathies arise?

Answer 4

Structural HB variants e.g. Hb S - single base substitution in global gene (altered function/structure)

Thalassaemias (alpha or beta) - reduce synthesis of normal global chain. Imbalance of alpha and beta chain production

Question 5

What maternal testing is performed in predicting fatal haemoglobinopathies/thalassaemia?

Answer 5

-genetic screening/counselling

Prenatal testing - chorionic villus biopsy and genetic diagnosis

Termination of affected pregnancy

Question 6

Pregnant women usually have physiological anaemia. Why?

Answer 6

Haemodilation

- plasma volume increases by 50% while RBC volume only by 25%

Question 7

Describe the changes that occur in haematological values in pregnancy

Answer 7

MCV increases - size of RBC - increased mobilisation of vit and mineral stores

Leucocytosis - neutrophilia (left shift)

Thrombocytopenia

Pregnancy = pro-thrombotic state (decreased fibrinolysis)

Anaemia

Question 8

How are haemoglobinopathies diagnosed?

Answer 8

FBC/FIlm

Haemoglobin electrophoresis

Question 9

What differences do we observe in film/Hb electrophoresis in individuals with structural Hb variants or with thalassaemia?

Answer 9

Strutural Hb variants - Hb electrophoresis identifies differences, sickled cell present on film

Thalassaemia - not observed in electrophoresis but in film, pale and small (microcytic/hypochromic)

Question 10

What is sickle cell disease cause by? i.e. genetic basis

Answer 10

Hb S - valine substitution for glutamine at position 6 on the Beta globin gene

Question 11

What type of anaemia is sickle cell anaemia?

Answer 11

Haemolytic - shorter lifespan - 10-20 days - release of Hb - irritant to vessels - inflammation and vasoconstriction

Question 12

What do sickled RBCs do?

Answer 12

At low oxygen tensions, Hb-s polymerise, forming tactoids which distort red blood cell - stick together and obstruct vessel - ischaemic damage

Question 13

What are the features (i.e. blood count, ratio of HbS:HbA, and clinical features) of heterozygous Hb (sickle cell TRAIT)?

Answer 13

HbS/HbA
Blood count = normal
Electrophoreses = HbS = 45%, HbA = 55%
Clinical features - normal except in extreme hypoxia/dehydration

Question 14

What are the features (i.e. blood count, ratio of HbS:HbA, and clinical features) of homozygous Hb (sickle cell DISEASE)?

Answer 14

HbS/HbS
- Blood count:anaemia (60-80g/L)
- Blood film: sickle cells
Hb electrophoresis: HbS = 95% HbA= 0%)

Question 15

hat are the acute complications of sickle cell disease?

Answer 15

Vado-Occlusive crisis - chest, bone, abdomen, brain, priapism (painful penis erection)

• Septicaemia
• Aplastic crisis
• Sequestration crisis (spleen,liver)

Question 16

What are the chronic complications of sickle cell disease?

Answer 16

• retinopathy
• Acute resp syndrome
  Haematuria and polyuria
• infections/autosplenectomy
• Avascular necrosis of long bones
• leg ulcers
• anaemia
• Jaundice and gallstones

Question 17

What is the treatment for sickle cell disease?

Answer 17

• Avoidance of precipitating factors of crises e.g. hypoxia/dehydration
• penecillin prophylaxis from 6 months
• RBC exchange transfusion - reduce Sickle cells
• pain management of crises (analgesics/opiates)
• Hydroxycarbamide increases-
  HbF. It reduces the tendency to acute sickle crises

Question 18

Broadly, what is thalassaemia?

Answer 18

• NOT structural abnormality
• synthesis of one of the global chains (Alpha/beta) is reduced

Chains are either ABSENT or synthesised at REDUCED rate

Question 19

What syndromes are associated with Alpha thalassaemia?

Answer 19

Hb Barts (4 gamma Hb) Hydrops fetalis - death in utero

HbH (tetramers 4 beta chains) - moderate microcytic,hypochromic anaemia

alpha trait - alpha plus (2x alpha nots and 2 aplha+) - no clinical consequences

Question 20

What is Beta thalassaemia? What are the two types?

Answer 20

Reduced rate of production of beta-globing chains (excess alpha chains)

-Thalassaemia minor - clinically normal

Thalassaemia intermedia - between mild and severe

Thalassaemia major - severe disease - can produce very little, if any, HbA

Question 21

What is the clinical diagnosis of an individual with beta thalassaemia intermedia?

Answer 21

Someone with a Hb level of 60-70g/L without need for blood transfusions

Question 22

What are the clinical features of beta thalassaemia minor?

Answer 22

Microcytic and hypo chromic cells (resembles iron deficiency)

Total Hb level normal/slightly reduced

No clinical problems

HbA2 level > 3.5%

Question 23

What are the clinical features of beta thalassaemia major?

Answer 23

Severe anaemia from a young age

Severe microcytic, hypochromic anaemia
Hb 30-60 g/L
Abnormal blood film with nucleated RBCs

Question 24

What are the symptoms of Beta thalassaemia major related to?

Answer 24

Symptoms related to severe anaemia and body’s increased production of RBCs to compensate

Question 25

What are the pathological features of beta thalassaemia major?

Answer 25

Defective Hb synthesis and haemolysis results in…

Increased bone marrow activity and bone marrow expansion to increase production - skeletal deformity and stunted growth

• Iron overload - (secondary to blood transfusion) damage organs and endocrine systems
• protein malnutrition
• Splenomegaly and hepatomegaly “extra medullary haemopoises”

Question 26

What signs are characteristic of beta thalassaemia major?

Answer 26

Thalassaemia faces

‘Hair on end’ X-ray, frontal bossing, maxillary hypertrophy

Due to expanded bone marrow

Question 27

What is the treatment for beta thalassaemia major?

Answer 27

Transfusion - maintain Hb 120 g/L to prevent excessive bone marrow RBC production (stops skeletal deformity and hepatosplenomegaly)

Iron chelation therapy

Bone marrow transplantation has been curative!

Question 28

What is the problem of blood transfusions in the treatment of beta thalassaemia major?

Answer 28

Iron overload - body has no mechanism to excrete iron

Gonad/hypothalamus - failure of puberty, growth failure

Liver - cirrhosis

Pancreas - diabetes

Heart - cardiomyopathy and heart failure

Question 29

What are the two iron chelation drugs?

Answer 29

DeFERIprone and deFERAsirox