Red Book - Sickle Cell

Question 1

Pathophys of sickle cell - genetics

Answer 1

Autosome recessive

Point mutation at position 6 on b-Hb gene on chromosome 11.

Valine is substituted for glutamate

Leads to fomration of Hb-S

Homozygous allele pts - severe disease (HbSS)
Heterozygous (HbAS)

Both resistant malaria

Question 2

Pathology of sickle cel

Answer 2

HbS is less solube and more viscous than HbA.

Tends to polymerise

Hypoxia worsens polymerisation —> forms in red cell, distorts red cell —> SICKLES

Abnormal cells breakdown —> haemolytic anaemia.

Causes microvascular thrombus and distal infarction —> sickle crisis

Question 3

SaO2 and PaO2 of sickling

Answer 3

HbSS - SaO2<85% (PO2 5.2 to 6.5)

HbAS - SaO2 < 40% (PO2 3.2-4.0)

Question 4

When is it apparent?

Answer 4

3-6 months then HbF—> HbA

Question 5

Catergorise the types of crisis

Answer 5

Veno-occlusive

Sequestriation

Aplastic

Question 6

Describe the veno-occlusive crisis

Answer 6

1) Acute chest syndrome
2) Stroke
3) Long bone iscahemia
4) abomdinal pain
5) AKI

Question 7

Describe the acute chest syndrome

Answer 7

Due to pulmonary infarcts

Acute ill with fever and resp distress
NEW PULMONARY INFITRATE

Presents like pneumonia —> cough, dyspnoea, haemoptysis

Resp failure and progress to ARDS

Most common cause of adult mortlaity

Question 8

Treatment of the acute chest syndrome

Answer 8

Rest, oxygen, iv fliuid, analgesia
(may be opiate tolerant —> adjuncts)

+/- broad spec Abx

Exchange transfusions

Question 9

What is sequestriation

Answer 9

Mainly in children

Sudden splenic sequestration

Worsening anaemia —> hypotension and enlarging spleen

In adults the spleen has infarcted (auto-splenectomy)
Need immunisation and abx prophylaxis

Question 10

Treatment of sequestriation

Answer 10

Fluid resus

Cautious transfusion

Aim to increase Hb by 20-30g/L

Question 11

What is the aplastic crisis

Answer 11

Red cell aplasia —> parvovirus B19 infection
Folate deficiency

Transfuse with rise of 20-30g/L

Question 12

Investigations for sickle

Answer 12

FBC - Hb 60-90 with evidence of reticulocytosis
HbAS may be normal

Blood film - sickling, target cells, Howell Jolly Bodies

Sickledex Test —> confirms presence of HbS but does not tell disese from trait

Hb Electrophoresis
GOLD STANDARD
Detects different Hb’s and proportions

Question 13

Managing acute chest

Answer 13

ABCDE etc

Goals:
Prevent more sickling (hypoxia, dehydration, acidosis)
Analgesia
Involve haematology

1) Oxygen and ventilatory support
NIV mayt reduce I&V need
Tube when - worsening hypoxia, severe dyspnoea, resp acidosis

2) fluid resus
3) Broad spec abx
4) if asthma - bronchodilators and steroids
5) Blood transfusion - early top up OR exchange

Question 14

Indications for exchagne transfusion

Answer 14

Acute chest syndrome

Stroke

Hepatic sequestions

MOF

Question 15

What blood transfusion and when

Answer 15

Early top up when mild disease Hb<70

Exchagne when
Deterioration despite tx
High Hb
Marked hypoxia

Target Hb 90-100 with <30% HbS