Haem Flashcards
What is sickle cell anaemia?
Chronic condition with sickling of RBCs caused by inheritance of HbS
Sickle cell disease: collective name given to haemoglobinopathies in which HbS is inherited
What is the aetiology of sickle cell anaemia?
What are the main forms of sickle cell anaemia
There are 3 main forms of sickle cell disease:
-
Sickle cell anaemia (HbSS): homozygous
- Virtually all Hb is HbS; small amounts of HbF; no HbA
- Disease severity varies à partly determined by levels of HbF
- Most patients have 1% HbF; some have 10-15% (reduced severity)
-
HbSC disease (HbSC):
- Inherit HbS from one parent and HbC from the other parent (a different point mutation in beta-globin) à no HbA
- Nearly normal Hb and fewer painful crises than HbSS, but may develop proliferative retinopathy in adolescence and osteonecrosis of hips/shoulders
-
Sickle beta-thalassaemia:
- Inherit HbS from one parent and beta-thalassaemia trait from the other
- No HbA à similar problems to sickle cell anaemia
-
Sickle cell trait: heterozygous
- One HbS and one normal beta-globin gene
- 40% Hb is HbS
- These people do not have sickle cell disease and are asymptomatic, but can transmit HbS to children
Which factors precipitate sickling in sickle cell anaemia
- infection,
- dehydration,
- cold,
- hypoxia,
- exercise,
- stress,
- acidosis
Which factors precipitate sickling in sickle cell anaemia
What is the epidemiology of sickle cell anaemia
Common in Africa, Caribbean, Middle East and areas with high prevalence of malaria (carrier protects against malaria)
What are the different presentations (signs & symptoms) of sickle cell anaemia
Presents at 3-6months (when HbF decreases)
- Signs of anaemia: lethargy, pallor, SOB
- Jaundice
-
Splenomegaly:
- Common in young children
- Less frequent in older children; may become smaller due to atrophy
Acute presentations:
-
Painful crises (vaso-occlusive crises):
- Pain in many organs of the body (usually bones of limbs and spine)
-
Hand-foot syndrome:
- Common presentation in late infancy
- Dactylitis with swelling and pain in fingers and/or feet from vaso-occlusion
-
Acute chest syndrome/chest crisis:
- Most serious type of painful crisis
- Can lead to severe hypoxia à mechanical ventilation and emergency transfusion
- May cause avascular necrosis of the femoral heads
-
Acute anaemia → sudden lethargy and pallor:
- Sudden drop in Hb, due to other crises
-
Sequestration crisis: sickled RBCs pool in spleen →
- sudden splenic or hepatic enlargement,
- abdominal pain
- circulatory collapse,
- infection (due to hyposplenism)
What are the different types of crises that can occur in sickle cell anaemia
- Painful crises (vaso-occlusive crises)
- Haemolytic crisis: sometimes associated with infection
- Aplastic crisis: e.g. due to parvovirus B19
- Sequestration crisis: sickled RBCs pool in spleen → sudden splenic or hepatic enlargement, abdominal pain and circulatory collapse, infection (due to hyposplenism)
Ix for sickle cell anaemia?
-
Screening:
- Prenatal CVS if high-risk
- Screened for in Guthrie test
-
Bloods: FBC, blood film
- Low Hb
- High reticulocytes in haemolytic crisis; low reticulocytes in aplastic crisis
- Sickle cells, anisocytosis, features of hyposplenism (target cells, Howell-Jolly bodies)
-
Sickle solubility test
- Reducing agent added to diluted blood, which converts oxyHb to deoxyHb, causing sickle cell formation (in trait and anaemia) à cloudy
- Gives rapid result but doesn’t differentiate between trait and anaemia à do electrophoresis
-
Hb electrophoresis
- Diagnostic test
- Shows HbS, absence of HbA (in HbSS) and increased levels of HbA2 and HbF
- Hip X-ray: common site for avascular necrosis of the femoral head
General Mx of sickle cell anaemia?
Conservative management:
- Advice:
- Avoid precipitating factors for vaso-occlusive crisis
- Good hygiene and nutrition
- Genetic counselling and prenatal screening
-
Infection prevention:
- Vaccination (incl. pneumococcus, Hib, meningococcus)
- Oral prophylactic penicillin through infancy and childhood
- Folic acid supplementation (due to increased cell turnover)
Hydroxycarbamide:
- Increases HbF production
- Children who have recurrent admissions for painful crises or acute chest syndrome may benefit
- Needs monitoring for SEs (esp WBC suppression)
RBC transfusions:
- For severe anaemia
- Aims to maintain HbS <30%
- Give iron chelators
- Top-up transfusions in aplastic/sequestration crisis (but makes painful crisis worse)
- Exchange transfusions in severe crises and before surgery
BM transplant
- The only cure
- Only in children with HLA-identical sibling
Mx of acute painful crisis in sickle cell anaemia?
Management of acute painful crisis:
- Oxygen
- Good hydration → oral or IV fluids as required
- Strong analgesia (may need IV opiates)
- Antibiotics if infection is suspected
- Exchange transfusion for acute chest syndrome, stroke and priapism
complications and prognosis of sickle cell anaemia?
Complications:
- Vaso-occlusion
- Splenic sequestration à leads to hyposplenism
- Aplastic crises (due to parvovirus B19)
- Haemolytic crises
- Infection
- Increased susceptibility to encapsulated organisms (pneumococcus, H. influenzae)
- Due to hyposplenism secondary to chronic sickling and microinfarction in the spleen
- Risk of overwhelming sepsis is greatest in early childhood
- Priapism (persistent infection)
- Can lead to fibrosis of corpus cavernosa and impotence à treat promptly with exchange transfusion
- Stroke (10%) and cognitive problems (20%)
- Heart failure (from chronic anaemia) and cardiomyopathy
- Gallstones
- Leg ulcers
- Complications of repeated transfusions (see thalassaemia)
Most survive to 50yo; mortality in children is mainly due to infection (3%) (stroke in adults)
What is G6PD deficiency?
Inherited deficiency of the enzyme G6PD, leading to increased susceptibility to haemolytic anaemia
It is an inherited metabolic disorder
Aetiology of G6PD deficiency?
Caused by various different mutations à different clinical features in different populations
- X-linked à predominantly affects males
- Heterozygote females are usually clinically normal (have half the G6PD activity)
- Females can be affected if homozygous or in some rare phenotypes
- Heterozygote females are usually clinically normal (have half the G6PD activity)
G6PD is the rate-limiting enzyme of the pentose phosphate pathway à prevents oxidative damage to RBCs
- RBCs lacking G6PD are susceptible to oxidant-induced haemolysis (predominantly intravascular)
Triggers for haemolysis in G6PD deficiency?
- Triggers for haemolysis:
- Infection (most common)
- Antimalarials (primaquine, quinine, chloroquine)
- Antibiotics (sulphonamides (incl co-trimoxazole), quinolones (ciprofloxacin), nitrofurantoin)
- Aspirin – in high doses
- Naphthalene (mothballs)
- Divicine (fava beans – aka broad beans)
