Sickle cell disease Flashcards
Define sickle cell disease.
Disease of red blood cells caused by an autosomal-recessive single gene defect in the beta chain of haemoglobin, which results in sickle cell haemoglobin (HbS).
How common is sickle cell disease? Who is affected?
- 1 in 200 births in England
- 8% of Afro-Caribbeans carry the sickle cell gene
- Presents after 4-6months in newborns
- Common in Africa, Caribbean, Middle East and areas of high prevalence of malaria
What are the genotypes and phenotypes of SCD?
Normal = HbAA
Sickle cell disease is a group of inherited conditions:
- beta S, beta S (HbSS**) = sickle cell **anaemia - mod/severe
- beta A, beta S (HbAS**) = sickle cell **trait - asymptomatic/mild
- beta A, beta A = normal
Other forms include a beta S gene and another abnormal gene e.g.
- Hb SC - heterozygote for HbS and HbC milder form of SCD - intermediate
- HbS/beta0 thal - severe (almost indistinguishable from SCA)
- HbS/beta+ thal - mild to mod
- HbS/hereditary persistence of fetal Hb (S/HPHP) - asymptomatic
- Rare combinations of HbS with HbD Los Angeles, HbO Arab, G-Philadelphia, among others.
What is the genetic abnormality in SCD?
Mutation in the beta globin gene, position 6
Switch from glutamate to valine
Renders Hb more likely to polymerise in a low oxygen state –> clumping –> vasoocclusive crises
What is SC trait? Does sickle cell trait produce symptoms?
There is typically 60% HbA and 40% HbS. Sickle cell trait protects against malaria.
Usually no - you only have one sickle gene. Sometimes associated with renal problems and renal medullary cancer.
Why is HbS problematic?
HbS behaves differently from HbA. Under certain conditions, HbS makes the red blood cells change shape - instead of the normal doughnut shape, they become sickle-shaped, like a crescent moon.
Conditions which trigger sickling –> crises are:
- cold,
- infection,
- lack of fluid in the body (dehydration),
- low oxygen, and
- acid (acid is produced in hard physical exercise).
The sickle cells are destroyed more easily than normal red blood cells –> moderate and persistent anaemia
When do symptoms of sickle cell anaemia start?
At 3-6 months. This is when HbF levels start to fall –> anaemia, jaundice, pallor, lethargy, growth restriction and general weakness
What investigations would you do to diagnose SCD?
Hb Electrophoresis (DIAGNOSTIC) - no HbA, HbSS 80-95%, 2-20% HbF
FBC - Hb between 6-8g/dL
Reticulocytes - 10-20%
Blood film - sickled erythrocytes and features of hyposplenism
Sickle solubility test - mix HbS with reducing solution –> turbid appearance due to precipitation of HbS. Normal Hb gives clear solution.
How do you manage a SCD crisis? What is the long term management?
Crisis:
- Hydration and
- Analgesia (morphine - not much else works) and and anti-emetics (cyclizine)
- Potentially transfusion in severe cases +/- iron chelation i.e. symptomatic anaemia
- +/- Exchange transfusion - for acute vaso-occlusion e.g. stroke, acute chest syndrome, multiorgan failure, splenic sequestration. Rapidly reduces HbS percentage.
- Antibiotics - ?infection
Long term
- Hydroxycarbamide/hydroxyurea (increases HbF, decreases platelets and WCC)
- Lifestyle modifications (avoid strenuous exercise)
- Counselling
- Supplementation - zinc, folic acid, vitamin D
What are the benefits and disadvantages of hydroxyurea?
Benefits:
- Cytotoxic so increases HbF** which is beneficial - increases Hb, decreases platelets and WCC, so is **prophylactic.
- Reduced risk of crises
- Reduced episodes of acute chest syndrome
- Reduced need for blood transfusions
Disadvantages:
- Teratogenic - stopped at least 3 months before conception
- Myelosuppressive
How do you prevent infections in SCD?
Oral penicillin - given at diagnosis (sometimes stopped after age 5yrs as risk of pneumococcal infection decreases)
Vaccinations - against haemophilus influenzae type B, and conjugated vaccines against strep. pneumoniae. Then unconjugated pneumococcal vaccine from age 2yrs every 3-5yrs and against meningococcus, influenza, hep B.
What are the complications of SCD?
- Vaso-occlusive crisis (painful, in the fingers and feet)
- Pulmonary hypertension
- Acute chest syndrome (SOB, chest pain, hypoxia, X ray evidence of consolidation)
- Splenic sequestration
- Anaemia (due to chronic haemolysis, 60-80g/L)
- Growth issues
- Osteomyelitis due to bone infarction (staph aureus)
- Vaso-occlusive leg ulcers
- Neuro (strokes, TIAs, epilepsy)
- Gallstones
Which type of infections are patients with SCD most susceptible to?
encapsulated bacteria such as pneumococcus (highest risk before age 3yrs)
What is an aplastic crisis and how does it present?
Aplastic crisis = temporary cessasion of erythropoiesis, causing severe anaemia
- usually precipitated by infection with parvovirus B19 → drop in Hb over about 1 week
- recovery may be spontaneous but a transfusion is usually required
- severe anaemia associated with an aplastic crisis patients may present with high-output congestive heart failure
What is acute chest syndrome?
Vaso-occlusive crisis affecting lungs
Defined as: new pulmonary infiltrate on CXR + one or more manifestation such as: fever, cough, sputum, tachypnoea, dyspnoea, new onset hypoxia.
