Courses - Australian Sickle Cell Advocacy Inc

Module 1

Module Introduction

This course provides understanding of SCD, recognition of symptoms, patient support/education, and management principles.

Learning Outcomes

Understand what Sickle Cell Disease (SCD) is
Inheritance pattern and mode of inheritance
Pathophysiology of SCD
Symptoms and clinical signs
How SCD is diagnosed
Principles of management and prevention

Self-care Lesson

Self-care module is marked as APNA use only: No.

Module 2

Sickle Cell Disease Background Information

2.1 What is sickle cell disease?

SCD is a group of inherited autosomal recessive disorders affecting haemoglobin and manifests when two abnormal haemoglobin genes are inherited, with at least one S gene.

Sickle cell trait means one sickle gene plus one normal gene, often without disease symptoms, but transmissible to offspring.

Sickle cell disease overview illustration — Source image from module content

2.2 Who is at risk of getting SCD?

5-7% of world population carry relevant mutation. Around 300,000 children are born with SCD each year, majority in Africa. Trait affects sub-Saharan Africa, Hispanic countries, South Asia, southern Europe, and Middle East populations.

Global risk distribution graphic — Source image from module content

2.3 Sickle Cell Disease in Australia

Rare disease in Australia with limited awareness and incomplete incidence data; expected prevalence rise due to migration trends from affected populations.

Sickle cell disease in Australia graphic — Source image from module content

2.4 History of Sickle Cell Disease

SCD present in Africa for at least five thousand years.
First blood results showing sickle cells.
1910: Herrick and Irons describe sickle-shaped red blood corpuscles.
1927: relation between sickling and low oxygen discovered.
1930s: pain linked to vessel blockage and ischaemia.
1949: hereditary nature demonstrated; molecular disease concept.
1951: abnormal haemoglobin structure identified in SCD.
1956: first genetic disorder with known molecular basis.
1970s: better tests and understanding developed.
1972: military screening and National SCA Control Act in US.
1975: New York introduces newborn screening.
1984: first reported cure after bone marrow transplant.
1995: hydroxyurea proven to reduce complications.
1998: hydroxyurea FDA approval for adults.
2017: Endari approved; pediatric hydroxyurea approval expanded.

History timeline figure 1 — History timeline visual

History timeline figure 2 — History timeline continuation

2.5 End of Lesson Assessment (Full)

What is sickle cell disease? a) inherited disorders affecting haemoglobin b) develops with two abnormal genes incl S gene c) mutation context d) All of the above e) None
Difference between SCD and SCT (select all): a and d are correct statements.
When first identified in lab? a 1927 b 1910 c 1930s d 1995 (Correct: 1910).

2.6 References

CDC - What is SCD
CDC - Sickle cell trait
Crighton et al. Intern Med J (2016)
Hematology.org
Serjeant GR. Br J Haematol. 2001

Module 3

Sickle Cell Disease Genetics

3.1 Mode of inheritance

Autosomal recessive disease; both copies must contain mutation
One copy = carrier (trait)
If both parents carriers: 25% SCD, 50% carrier, 25% unaffected

Inheritance of Sickle Cell Disease figure — Fig 3: Inheritance of Sickle Cell Disease

3.2 Haemoglobinopathies process

Hb has alpha and beta chains; HBB gene makes beta-globin
Mutations produce variants: HbS, HbC, HbD, HbE
Thalassaemias and structural variants are key groups
HbS mutation: glutamic acid to valine at position 6
Consequences: polymerization, vaso-occlusion, endothelial dysfunction, inflammation

Production of abnormal haemoglobins figure — Fig 4: Production of abnormal haemoglobins

3.3 Types of SCD (Accordion)

HbSS: usually most severe.
HbS/beta thalassaemia: beta0 usually severe, beta+ often milder.
HbSC disease: generally milder form.
Other less common: S/HPFH, HbS/HbE and rare combinations.

3.4 Assessment + 3.5 References

Assessment includes recessive inheritance meaning, commonest type (HbSS), and beta thalassaemia type differentiation.

References include MedlinePlus, GOV.UK handbook/introduction, HBB gene source, and CDC fact page.

Module 4

Pathophysiology of Sickle Cell Disease

4.1 RBC overview and marrow formation

RBCs originate from bone marrow stem cells; lifespan around 120 days; flexible biconcave design supports microcirculation.

4.2 Haemoglobin and SCD red cells

Normal adult Hb: HbA, HbA2, HbF proportions
SCD red cells sickle under deoxygenation due to HbS polymerization
Recurrent sickling damages membrane, increases adhesion and viscosity

Structure of adult haemoglobin figure — Fig 6: Structure of adult haemoglobin

4.3 Pathogenesis factors process

HbS polymerization
Impaired biorheology and adhesion-mediated vaso-occlusion
Haemolysis-mediated endothelial dysfunction
Sterile inflammation, hypercoagulability, oxidative stress
NO depletion and arginine metabolism defects
Gardos channel abnormalities and dehydration predisposition

Pathophysiology of Sickle Cell Disease figure — Fig 7: Pathophysiology of Sickle Cell Disease

Pathogenesis factors of Sickle Cell Disease figure — Fig 8: Pathogenesis factors of Sickle Cell Disease

4.4 Clinical implications

Chronic haemolytic anaemia and microvascular vaso-occlusive episodes cause end-organ ischemia-reperfusion injury and infarction.

Clinical manifestations of Sickle Cell Disease figure — Fig 9: Clinical manifestations of Sickle Cell Disease

Hand and Foot syndrome figure — Fig 10: Hand and Foot syndrome

4.5 Assessment + 4.6 References

Assessment covers red cell nature, blood component affected (haemoglobin), and vaso-occlusion true/false.

References include MSD manual, UCSF, GOV.UK, AMSJ, and MDPI review.

Module 5

Clinical Features and Complications of SCD

5.1 Symptoms and signs

Early infancy often asymptomatic due to HbF persistence
Chronic haemolysis signs: fatigue, pallor, jaundice, tachycardia
VOC manifestations: acute/chronic pain, bone pain, dactylitis

5.2 Complications

Acute chest syndrome
Aplastic crisis and splenic sequestration
Infections from functional asplenia
Musculoskeletal and avascular necrosis
Cardiac and pulmonary hypertension
CNS stroke/TIA and silent infarcts
Gastrointestinal, renal, skin and growth complications
Psychosocial effects: anxiety, depression, quality-of-life decline

Most severe complications require urgent treatment and discussion with on-call Haematology consultant.

5.3 Assessment + 5.4 References

Most common manifestation: vaso-occlusive crisis.
Psychosocial complications occur in both children and adults.
Avascular necrosis = joint narrowing and collapse due to infarction.

References include RCH guideline, NHS, Mayo Clinic, and AJN review.

Module 6

Diagnosis of Sickle Cell Disease

6.1 Diagnosis

Higher carrier risk in specific ethnic backgrounds; carrier screening should be discussed during pre-pregnancy and prenatal care.

Laboratory diagnosis illustration — Laboratory diagnosis visual

6.2 Laboratory diagnosis process

First-line: CE, HPLC, IEF
Confirmation: alternate method and possible solubility test
Definitive: tandem mass spectrometry, DNA testing, sequencing

6.3 Antenatal screening and newborn screening

Pre-conception counseling for identified mutation carriers
Ideal timelines for antenatal screening and PND windows
Low/high prevalence screening pathway differences
Special cases: donor gametes, adoption, bone marrow transplants
PND methods: CVS, amniocentesis, non-invasive evolving methods
Universal newborn screening available in multiple countries
Australia implementation process referenced in source text

6.4 Assessment + 6.5 References

Assessment covers genetics test definition, prenatal diagnosis question, and newborn screening availability statement.

References include MedlinePlus, review articles, NHS screening sources, and Australian health program source.

Module 7

Management of Sickle Cell Disease

7.1 Overview of management

WHO recognition of hemoglobinopathies as major public health issue; improved outcomes due to vaccination, screening, hydroxyurea, transfusion, and intensive care frameworks.

7.2 Aim of management

Prevention of symptoms, especially pain episodes
Management of complications and organ dysfunction
Prevention of future complications

7.3 Preventive care process

Multidisciplinary specialist care model
Patient education for early VOC detection and danger signs
Trigger education: hypoxia, dehydration, temperature change, stress, infection
Self-care behaviors: hydration, warmth, avoid extreme exertion/high altitude
Medication adherence, counseling, and appointment follow-up
Infection prevention and vaccination (pneumococcal/meningococcal/HiB etc.)

7.4 Symptom control

Prompt fluids and analgesia for VOC
Hydroxyurea and transfusion as major disease-modifying approaches
HSCT as current curative option
Gene therapy as evolving curative pathway

7.5 to 7.8 Therapies (Accordion)

Hydroxyurea: increases HbF, reduces crises/admissions; monitor cytopenias.
Voxelotor: Oxbryta withdrawn globally in 2024 due to safety concerns.
L-Glutamine (Endari): approved in 2017; oxidative stress pathway target.
Stem Cell Replacement: curative but limited by donor availability/toxicity.
Gene therapy: CRISPR-era approvals (e.g., Casgevy) noted; local availability varies.

7.9 Assessment + 7.10 References

Assessment includes VOC management, curative options, and 2017 drug identification (Endari).

References include Orphanet, RCH, CDC, NHS, Mayo Proc paper, FDA links and gene therapy sources.

Module 8

Module Conclusion Content

8.1 End of module assessment

Final 10-question MCQ includes hydroxyurea timeline, sickling low oxygen timeline, risk populations, pain mechanism timeline, beta-globin abnormality, bone marrow production site, complications set, prevention strategies, first SCD medication, and CRISPR approval year.

8.2 Australian Sickle Cell Advocacy Inc

ASCA overview, establishment details, state affiliates, and objectives including stigma reduction, awareness, screening advocacy, national guidelines, surveillance database, PBS medication access, service recognition, and fundraising support.

Australian Sickle Cell Advocacy illustration — ASCA section image

8.3 End of module summary

Learners should understand SCD definition, inheritance, pathophysiology, symptoms/signs, diagnosis, and management/prevention principles.

8.4 Scope of Practice

APNA use only: No. Scope guidance and referral to specialist services retained as policy reminder.