Sickle Syndromes Flashcards
Define sickle syndrome
Group of genetic disorders that affect the structure of haemoglobin, resulting in the production of HbS
What is the genetic cause of sickle cell disease?
A point mutation in codon 6 of the beta-globin gene which substitutes glutamine with valine, producing HbS
How does HbS differ from normal haemoglobin?
HbS polymerises under low oxygen conditions, which distorts the red blood cell, damages the membrane, and causes vaso-occlusion and hemolysis
What is the difference between sickle cell trait (HbAS) and sickle cell anaemia (HbSS)?
Sickle cell trait (HbAS)
→ Asymptomatic carrier state, with less than 50% HbS and no polymerisation unless under severe hypoxia.
Sickle cell anaemia (HbSS)
→ Homozygous for HbS, with >80% HbS, causing sickle crises and chronic hemolysis
What triggers a sickle crisis?
Hypoxia
Dehydration
Infection
Cold exposure
Stress/fatigue
What is produced by the mutation in sickle cell disease?
HbS (sickle hemoglobin)
What is sickle cell trait (HbAS)?
It is an asymptomatic carrier state with less than 50% HbS
What happens in sickle cell anaemia (HbSS)?
HbS > 80% and causes sickle crises and chronic hemolysis
What is a common feature of a sickle crisis?
Vaso-occlusive crises causing acute pain
What is acute chest syndrome in sickle cell disease?
A serious complication with shortness of breath, chest pain, fever, and new lung findings
What causes splenic sequestration in sickle cell anaemia?
Vaso-occlusion and enlargement of the spleen
What are the common investigations for sickle cell disease?
FBC
Hb electrophoresis or HPLC
Blood film to see sickled cells
How is sickle cell anaemia managed long-term?
(1) Prophylactic penicillin
(2) Vaccinations
(pneumococcus, meningococcus)
(3) Folic acid supplementation
(4) Hydroxycarbamide and transfusions
What is the treatment during a sickle crisis?
(1) Oxygen (15L/min)
(2) Morphine for pain
(3) Hydration and rest
(4) Antibiotics if infection is present
(5) Red cell exchange transfusion in severe cases
How does HbAS differ from HbSS in clinical presentation?
HbAS is usually asymptomatic, while HbSS presents earlier with severe sickle crises
What are gallstones caused by haemolysis referred to as?
Pigment stones
Give 2 examples of a disease inherited in an autosomal dominant manner
(1) Huntington’s
(2) Von Willebrand’s Disease
Which virus causes an aplastic sickle cell crisis?
Parvovirus B19
Give 2 examples of a disease inherited in an autosomal recessive manner
Cystic Fibrosis, Sickle Cell Disease
The primary feature of vaso-occlusive crises is what?
Pain
What is the most common cause of death in sickle cell disease?
Acute chest syndrome
How can Vaso-occlusive crises be triggered?
May be triggered by local hypoxia (eg. in cold weather)
Definitive diagnosis of sickle cell disease is with what?
haemoglobin electrophoresis +/– genetic testing
An 18-year-old man with sickle cell disease presents with rapid-onset weakness and fatigue. He looks pale but otherwise examination is unremarkable.
Blood tests are performed:
Blood test Result Normal range
Haemoglobin 82 g/L 130-180 g/L
(MCV) 94 fL 80-100 fL
WCC 4.0 x109/L 4-11 x109/L
Platelets 140 x109/L 150-400 x109/L
Reticulocytes <0.1% 0.2-2%
What complication of sickle cell disease is this patient experiencing?
Aplastic crisis
= Low Hemoglobin, Low Reticulocyte Count, Normal White Cell Count and Platelets
= This patient is experiencing an aplastic crisis, likely triggered by a viral infection (e.g., parvovirus B19), leading to bone marrow suppression and inadequate red blood cell production
Sickle cell disease is common in individuals of Central and West African descent and is implicated in malaria resistance. What best describes the mechanism by which sickle cell disease causes pathology?
Sickle cells block the microcirculation causing a vaso-occlusive crisis
A 25-year-old man with known sickle cell anaemia presents to the emergency department with his 4th painful crisis in the past 12 months.
He is treated and stabilised with analgesia, IV fluids and oxygen. He is reviewed by a haematologist who suggests that he should be started on long-term prophylactic therapy.
What is the single most appropriate long-term prophylactic therapy for this patient?
Daily oral hydroxyurea
A 28-year-old man presents to haematology outpatients. He has a long history of chronic and unexplained limb pain and is concerned he may suffer from sickle cell anaemia. On examination there is long-bone tenderness in the right leg, but nil else of note. His younger sister was diagnosed antenatally with sickle cell anaemia and suffers from mild disease with 1-2 vaso-occlusive crises every 3-5 years. A full blood count performed by the GP shows microcytic anaemia and mild reticulocytosis.
What is the single best diagnostic test?
Haemoglobin electrophoresis
A 24-year-old woman comes into the GP surgery requesting testing for a genetically inherited disease. Her female cousin has been diagnosed with the disease, her father is known to be a carrier but neither she nor her brother is affected.
What is the pattern of inheritance?
Autosomal Recessive
On examination he is tachypnoeic, de-saturating to 91% on air and has a widespread polyphonic wheeze on auscultation. He had been well until 7 days previously when he developed a low-grade flu-like illness which has since worsened. He is not on any regular medications.
Given the likely cause of this man’s symptoms, why would the correct answer be High-flow oxygen, antibiotics and set up for an urgent exchange transfusion instead of High-dose oral hydroxycarbamide
Hydroxycarbamide is used in sickle cell disease but for long-term prevention of acute chest crises. It has little-to-no role acutely
The core triad of acute chest crisis management is high-flow oxygen, antibiotics (with atypical cover) and exchange transfusion. Long-term this patient should be started on hydroxyurea
How would you know the patient has acute Chest Syndrome?
- Low oxygen levels (hypoxia) or respiratory acidosis on blood gas.
- Leukocytosis
= elevated white blood cells - Increased inflammatory markers
= CRP, ESR - Key Indicator: Hypoxia, abnormal chest X-ray findings, respiratory distress and pulmonary symptoms
How would you be able to tell if it’s a Haemolytic Crisis?
- Low haemoglobin
- Elevated reticulocytes
- Elevated bilirubin
- Normal white blood cell count (unless there’s an infection).
- Key Indicator: Elevated reticulocytes and elevated bilirubin.
How would you be able to tell it is a Parvovirus B19 Infection?
- Low haemoglobin (significant anaemia).
- Very low reticulocytes
- Normal or slightly elevated white blood cell count
- Normal platelets (or mildly low).
- Key Indicator: Low reticulocyte count despite significant anemia.
How would you be able to tell if its an Aplastic Crisis?
- Low haemoglobin (severe anaemia).
- Extremely low reticulocyte count (<0.2%, normal range is 0.2–2%).
- Normal white blood cell count
- Normal platelets (unless other underlying issues).
- Key Indicator: Severe anaemia with very low reticulocytes and no marrow response.
How would you be able to tell if its a Splenic Sequestration Crisis?
- Low haemoglobin (rapid drop in RBCs due to sequestration).
- No increase in reticulocytes (because the spleen is trapping RBCs, not producing more).
- Normal white blood cells (unless infection is present).
- Platelets may be normal or low.
- Key Indicator: Sudden drop in haemoglobin and splenomegaly (on clinical examination or ultrasound)
If a patient with sickle cell disease presents with sudden severe anaemia and very low reticulocyte count without viral symptoms. What is the most likely diagnosis?
aplastic crisis
If a patient with sickle cell disease presents with sudden severe anaemia and very low reticulocyte count with/without viral symptoms. But they also have a history of fever, rash, or joint pain. What is the most likely diagnosis?
parvovirus B19 infection
Chest pain or breathing indicates what?
acute chest syndrome
Jaundice or rapid anaemia with high reticulocytes indicates what?
Likely hemolytic crisis
Pallor and low reticulocytes with normal white count indicate what?
Likely aplastic crisis (often due to parvovirus)
Fever and organ-specific symptoms (e.g., joint pain, rash) indicate what?
Parvovirus B19
Splenomegaly and shock indicate what?
Splenic sequestration crisis
A 21-year-old man attends the haematology clinic. He has a history of sickle cell disease, with infrequent sickle cell crises that can be managed at home with hydration and simple analgesia. He takes no regular medications. What type of sickle cell disease is this describing and what would be the haemoglobin gene that represents this?
mild
= HB SC
Hb SS is if it’s major
Hb AS is the sickle cell trait
Hb AA is normal
HbS
Sickle haemoglobin
HbAS
Sickle cell trait
HbSC
Milder than HbSS (sickle cell disease) but can still cause symptoms like anaemia, mild sickling, or vaso-occlusive events
HbSS
Sickle cell disease
Why is Hydroxyurea the most appropriate long-term prophylactic therapy?
(1) Increases fetal haemoglobin (HbF) production, reducing red blood cell sickling and vaso-occlusive crises.
(2) It is recommended for patients with frequent painful crises (≥3 per year), severe disease, or complication
A 20-year-old man with a background of sickle cell disease attends the emergency department with a one-day history of fever and feeling generally unwell. He has a history of multiple sickle cell crises.
Which pathogens is the patient most susceptible to?
Encapsulated bacteria
= (1) Streptococcus pneumoniae
(2) Haemophilus influenzae
(3) Neisseria meningitidis
A seven-month-old infant presents to the emergency department with acute abdominal pain and distension on a background history of lethargy, growth restriction, and general weakness.
Abdominal examination identifies splenomegaly. The infant is sent for a series of investigations and is subsequently diagnosed with sickle cell disease, with the acute presentation thought to represent an acute crisis.
Which of the following is the most likely haemoglobin trait in this patient?
HBs HBs
