Sickle Cell Anaemia

Question 1

Where is Sickle Cell Anaemia common

Answer 1

Africans - India, Middle East + southern Europe

Question 2

Inheritance pattern of SCA

Answer 2

Autosomal Recessive

Question 3

How is it caused

Answer 3

Production of abnormal beta-globing chains

Question 4

Chances of getting the disease

Answer 4

1 in 4

Question 5

Chance of being a carrier

Answer 5

50%

Question 6

Chance of being disease free

Answer 6

1 in 4

Question 7

Risk factors of SCA

Answer 7

African

Family History

Question 8

Genetic mutations that cause SCA

Answer 8

Single-base mutation of Adenine to Thymine which substitutes Valine for Glutamic Acid at 6th codon of beta-globing chain

Question 9

What is the heterozygous state called

Answer 9

Sickle cell trait

Question 10

Why does SCA not manifest until 6th month of age

Answer 10

Because currently baby is running on HbF which is normal - starts becoming a problem when HbF starts to decrease

Question 11

Properties of HbS

Answer 11

Insoluble and polymerises when deoxygenated

Question 12

What happens to flexibility of cells

Answer 12

Decreases + become rigid

Question 13

Initially, is sickle cell process reversible

Answer 13

Yes

Question 14

How does this become an irreversible process

Answer 14

Cells eventually lose membrane flexibility with repeated sickling (become dehydrated and dense - won’t return to normal when oxygenated)

Question 15

How does sickling effect lifespan of RBS

Answer 15

reduced due to haemolysis

Question 16

How does sickling effect circulation

Answer 16

Impaired passage through microcirculation -> infarctions

Question 17

What precipitates sickling

Answer 17

Infection
Cold
Dehydration
Acidosis
Hypoxia

Question 18

Affinity of HbS to oxygen

Answer 18

Low - easily dissociates oxygen to normal RBCs - patients feel well even though anaemic

Question 19

Clinical presentation of heterozygous sickle cell trait

Answer 19

Asymptomatic

Question 20

When are sickle cell trait people disabled

Answer 20

Hypoxia (vasco-occlusive events will occur)

Question 21

What benefit does sickle cell trait have

Answer 21

Falciparum Malaria

Question 22

Why is acute pain felt in the hands and feet in SCA

Answer 22

Vado-Occlusion of small vessels and avascular necrosis of bone marrow of children

Adults - pain along long bones due to avascular necrosis of bone marrow

CNS infarctions - strokes in children

Question 23

What is acute chest syndrome

Answer 23

Pulmonary hypertension and chronic lung disease due to faso-occlusive crisis of pulmonary vasculature

Question 24

What is Acute chest syndrome caused by

Answer 24

Infection, fat embolism from necrotic bone marrow or pulmonary infarction due to sequestration of sickle cells

Question 25

What is sequestration of sickle cells

Answer 25

Sickle cells gets trapped in pulmonary vasculature

Question 26

Signs of ACS

Answer 26

shortness of breath, chest pain and hypoxia

Question 27

What defines pulmonary hypertension

Answer 27

Pulmonary artery pressure greater than 25 mmHg by right heart catheterisation

Question 28

How common is pulmonary hypertension in SCA

Answer 28

affects 10%

Question 29

What bacteria can cause acute chest syndrome

Answer 29

Chlamidyia Mycoplasma Strep. pneumoniae

Question 30

How does HbS cause anaemia

Answer 30

Splenic sequestration (sickle cells get trapped in spleen) - acute enlargement of spleen that is painful and fall in Hb Bone marrow aplasia - rapid fall in haemoglobin with no reticulocytes in the peripheral blood because of the failure of erythropoiesis in the marrow

Question 31

How does splenic sequestration effect the spleen

Answer 31

Leads to a fibrotic, non-functioning spleen

Question 32

When does bone marrow aplasia follow

Answer 32

Follows infection with Erythrovirus B19 which invades proliferating erythroid progenitors

Question 33

Problems of SCA on growth + development

Answer 33

Young children start short + become normal height by adulthood Remain below normal weight Sexual maturation is delayed

Question 34

Long-term problems on bones

Answer 34

1. Vaso-occlusive crises = avascular necrosis of hips + shoulders, compression of vertebrae and shortening of bones in hands and feet Osteomyelitis

Question 35

Why would osteomyelitis occur

Answer 35

Due to Staph A, Staph. pneumonia and salmonella

Question 36

Long-term cardiac issues

Answer 36

Cardiomegaly, arrhythmias, iron overload myocardipathy MI

Question 37

Long-term near issues

Answer 37

TIA, fits and coma

Question 38

How does SCA effect liver

Answer 38

Chronic hepatomegaly, liver dysfunction due to trapping of sickle cells

Question 39

How does SCA effect Renal

Answer 39

Chronic tubulointerstitial nephritis

Question 40

How does SCA effect Eye

Answer 40

Retinopathy, vitreous haemorrhage and retinal detachments

Question 41

How does SCA effect pregnancy

Answer 41

Impaired placental blood flow - abortion

Question 42

Blood count

Answer 42

Hb range 60-80 g/L | Raised reticulocyte count

Question 43

Blood film

Answer 43

Sickled erythrocytes shown

Question 44

Result of sickle solubility test

Answer 44

POSITIVE

Question 45

How does Hb electrophoresis confirm diagnosis and when is it done

Answer 45

Shows 80-95% HbS and absent HbA At birth

Question 46

How is it treated

Answer 46

Precipitating factors controlled Folic Acid TO ALL

Question 47

How are acute painful attacks treated

Answer 47

1. IV fluids 2. Analgesia (NSAIDS, morphine) 3. Oxygen and antibiotics

Question 48

How is anaemia treated

Answer 48

1. Blood transfusion (risk of iron overload) | 2. ORAL HYDROXYCARBAMIDE)

Question 49

Role of Oral Hydroxycarbamide

Answer 49

Increases hbF conc.