Sickle Cell Disease

Question 1

Pathogenesis of HbS?

Answer 1

Single point mutation in the Hb synthesis where Valine replaces Glutamic acid at position 6 in the beta chain.

Question 2

Pathogenesis of HbC

Answer 2

Lysine replaces Glutamic acid at point 6 of Chromosome 11

Question 3

How is the Sickling test performed?

Answer 3

2% Sodium metasulphite is added to the blood to indicate presence of HbS

Question 4

Exceptions to Sickling test

Answer 4

Not useful in newborns
Results are either negative or positive

Question 5

What test is definite for Hemoglobinopathies?

Answer 5

HB electorphoresis

Question 6

What is HB electrophoresis?

Answer 6

It is a separation test.
Cellulose acetate electrophoresis pH 8.6 is the commonest.

Question 7

How do you use Hb electrophoresis to diagnose thalassemia?

Answer 7

HbA2 > 5% shows thalassemic trait.

Question 8

How do you diagnose Sickle cell?

Answer 8

Sickling test
HB electrophoresis
Fetal blood sampling ( pre- natal diagnosis)

Question 9

What factors affect severity of SCD?

Answer 9

1. Levels of HbF
2. Other associated RBC enzyme deficiency like G6PD deficiency which leads to repeated hemolysis.
3. Environment. Infections precipitate crisis
4. Good nutrition and prompt medical care

Question 10

Clinical presentation of SCD?

Answer 10

-Pain
- Bacteremia- early part of life.
- Acute chest syndrome- childhood to adolescence.
- Acute sequestration crises- 10years
- Stroke
-Chronic organ damage.

Question 11

Signs of SCD in childhood.

Answer 11

Pallor
Jaundice
Hepatosplenomegaly
Hand and foot syndrome (dactylitis)
Painful swollen feet and hands

Question 12

Examples of recurrent episodes of Acute events

Answer 12

1. Vaso-Occlusive Pain Crisis (VOPE)
2. Infarctive crises

Question 13

What is VOPE?

Answer 13

Occlusion of vessels by sickled cells resulting in pain from ischemic tissue injury/infarction.
Release of inflammatory mediators, activation of afferent nerve fibers.
Mostly affects long bones, abdomen, chest and back.

Question 14

Causes of VOPE?

Answer 14

Infection
Physical exertion
Exposure to extremes of weather
Fever
Dehydration

Question 15

X’tics of infarction crises

Answer 15

Bone pain
Acute abdominal pain(acute cholecystitis)
Acute chest syndrome
Priapism

Question 16

How do you manage pain crises?

Answer 16

1. Identify and treat underlying cause
2. Hydration- oral/IV infusion(D/S or N/S) at one and half maintenance.
3. Analgesics based on severity of pain
4. Massaging,
5. Application of heat

Question 17

What analgesics do you give in Pain crises?

Answer 17

1. Mild- non opioids like p’mol,
2. Moderate- NSAIDs + p’mol
3. Severe- opioids

Question 18

Features of Acute Anemic Episodes

Answer 18

1 Hyperhemolytic crisis
2. Aplastic Crises
3. Acute sequestration crises
4. Megaloblastic changes

Question 19

What is Hyperhemolytic crises?

Answer 19

Life span of HbS rbc is 10-20 days
Causes: infection, G6PD deficiency which worsens the hemolysis.

Question 20

Features of Hyperhemolytic crises

Answer 20

Low Hb, PCV
Increased retic count
Pallor
Hepatosplenomegaly
Jaundice
Cola-like urine

Question 21

What is Aplastic crises?

Answer 21

Acute failure of erythropoiesis

Question 22

Features of aplastic crises

Answer 22

Low Hb, PCV,
Low or absent retic count
Ass with parvovirus B19 infection

Question 23

Treatment for Aplastic crises

Answer 23

Packed rbc transfusion

Question 24

What is Acute sequestration crises?

Answer 24

Sudden progressive anemia accompanied by painful splenic enlargement and hypovolemic shock due to pooling of blood in the spleen which results in splenomegaly by >2cm and drop in Hb > 2 gm
This can also occur in the liver

Question 25

Clinical presentation of acute chest syndrome

Answer 25

Chest pain Fever Signs of respiratory distress New pulmonary infiltrate on chest X-ray

Question 26

What megaloblastic changes occur in SCD?

Answer 26

Chronic hemolysis leads to folate deficiency

Question 27

How is acute chest syndrome managed?

Answer 27

Clinically treated as infection (pneumonia) or infarction Broad spectrum Antibiotics + macrolides Analgesics Hydration Oxygen/ventilation Chest physiotherapy + incentive spirometry Bronchodilators Blood Transfusion Steroids-

Question 28

What makes one susceptible to infections?

Answer 28

Splenic hypo function Defective opsonization Abnormal phagocytic function against encapsulated organisms, pneumococcus and salmonella Impaired humoral antibody response Necrotic tissue from recurrent vaso-occlusion esp in salmonella osteomyelitis.

Question 29

How do you manage pneumococcal infection?

Answer 29

Penicillin prophylaxis after 8 weeks of life Oral penicillin (125mg po BID for all children < 3 years), 250 mg BID for children > 2 years Vaccines: pneumovax

Question 30

How do you manage pneumococcal infection?

Answer 30

Penicillin prophylaxis after 8 weeks of life Oral penicillin (125mg po BID for all children < 3 years), 250 mg BID for children > 2 years Vaccines: pneumovax Prevar vaccine

Question 31

Presentation of SCD in the Genitourinary System

Answer 31

Renal Priapism

Question 32

Renal manifestations

Answer 32

1. Papillary necrosis- loss of concentration ability 2. Hyposthenuria( low SG of urine) leading to polyuria, nocturia and enuresis 3. Nephrotic syndrome 4. Renal infarction 5. Pyelonephritis 6. Renal modeling carcinoma

Question 33

Priapism

Answer 33

2 types 1. Stuttering- short- lasting/ self - limiting bouts with many episodes 2. Major episode/ refractory May lead to impotence

Question 34

Treatment of Genitourinary manifestations

Answer 34

- conservative pain relief, hydration, transfusion, alkalization, exercises, hot baths. - Surgery

Question 35

Bone and Joint manifestations

Answer 35

1. Bone marrow expansion Increased erythropoiesis -> frontal/ bossing, gnathopathy. 2. Avascular necrosis- especially of the femoral head. 3. Osteomyelitis- humerus, radius, ulna, femur. Salmonella, staph aureus. 4. Leg ulcers- common in adolescents and young adults. Malleolar areas

Question 36

Eye manifestations

Answer 36

Retinopathy- retinal detachment

Question 37

Growth manifestations

Answer 37

Delayed puberty by 2 years Poor and stunted growth

Question 38

CNS manifestations

Answer 38

- headache - Stroke - convulsions - drowsiness - coma dysphasia - visual disturbance - hemiplegia, monoplegia, tetraplegia - child with painless limp - infarctive stroke- occlusion of vessels - moya moya: hemorrhagic stroke-> rupture of aneurysms formed in the circle of willis.

Question 39

Outcome of stroke in SCD

Answer 39

1. Immediate 2. Long term neurologic outcome

Question 40

Stroke prevention

Answer 40

Chronic transfusion Hydroxyurea

Question 41

Outcome of transfusion therapy

Answer 41

Iron overload

Question 42

How is stroke managed in SCD?

Answer 42

Transcranial Doppler ultrasound t - ICA/MCA velocity - Normal < 170cm/s - conditional > 170cm/s < 200cm/s - Abnormal > 200cm/s leads to chronic transfusion therapy/ Hydroxyurea therapy Headaches High Hb > 10 * increase HbF - Hydroxyurea Voxeletol (oxybryte)