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Sickle Cell Disease Flashcards

1
Q

Define Sickle Cell Disease

A

Inherited genetic defects in the beta-chain of Hb leading to a sickled haemoglobinopathy

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2
Q

Describe all the conditions caused by Sickle Cell Disease

A

Sickle Cell Anaemia (both beta chains are sickled HbS - autosomal recessive - most severe)

Sickle Cell Trait: (mild sickling seen but no disease/symptoms)

  • HbAS (one normal beta chain and one sickle)
    • this confers protection from malaria
  • HbSC - one beta chain is sickled and other is C)
  • HbSß (beta chains are HbS and thalassaemia)
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3
Q

Explain the aetiology / risk factors of sickle cell disease

A
  • Autosomal recessive mutation of the beta chain of haemoglobin
  • Glutamate (soluble & polar) is substituted for Valine (insoluble & non-polar)
  • Deoxygenation of HbS alters the conformation resulting in sickling of red cells, this makes the red cells more fragile and inflexible
  • Sickled red cells are prone to:
    • Cause vaso-occlusion leading to more hypoxia and more sickling
    • Polymerising and causing intravascular haemolysis and splenic sequestration
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4
Q

What factors precipitate sickling?

A

I, CHAD

  • Infection
  • Cold
  • Hypoxia
  • Acidaemia
    • in acidic conditions, most likely caused by CO2, Hb releases oxygen so becomes deoxy-Hb
  • Dehydration
  • Extreme activity
  • Psychological stresses
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5
Q

Summarise the epidemiology of sickle cell disease

A
  • Up to 10% of Caribbeans and 25% of Africans (sub-Saharan) carry the sickle gene
  • Distribution matches that of endemic Plasmodium falciparum malaria
  • Around 200,000 affected births annually worldwide
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6
Q

Recognise the presenting symptoms of sickle cell disease (3 classes of symptoms)

A

VASO-OCCLUSION/INFARCTION/PAINFUL CRISES Symptoms

  • Abdominal pain (mesenteric ischaemia)
  • Bone Pain
    • Due to BONE INFARCTION/AVASCULAR NECROSIS most commonly affecting humeral/femoral head
    • Pain due to OSTEOMYELITIS in ribs, femur, spine, pelvis -most common infective sequelae
  • Visual floaters (vaso-occlusion in retinal arteries can lead to haemorrhage & neovascularisation)
  • Acute Chest Syndrome (pulmonary vaso-occlusion → presents with dyspnoea/tachypnoea, chest pain, cough, hypoxia and new pulmonary infiltrates seen on chest x-ray – indistinguishable from pneumonia
  • Haematuria (due to papillary necrosis - papilla receive urine from collecting ducts)
  • Hyposthenuria (can’t concentrate urine –> polyuria –> dehydration)
    • Increased nocturnal enuresis
  • Priapism (vaso-occlusion of the penile venous drainage)

SEQUESTRATION Symptoms

  • Fever/Infection (hyposplenism due to splenic sequestration, blood flowing to spleen becomes trapped due to sickle)
  • Acute splenic sequestration: pallor, shock, tachycardia, and lethargy - hypovolaemic symptoms - dramatic drop in Hb

HAEMOLYTIC ANAEMIA symptoms

  • Fatigue
  • Dyspnoea
  • Gallstone pathology: ascending cholangitis, cholecystitis, gallbladder empyema (pigmented bilirubin gallstones)

APLASTIC CRISIS: Co-infection with parvovirus B19, causes a dramatic drop in Hb with low/normal reticulocyte count. Patient will feel lethargic

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7
Q

Recognise the signs of sickle cell disease on physical examination

A

VASO-OCCLUSIVE

  • Fever (splenic atrophy)
  • Retinal cotton-wool spots
  • Neurological/Stroke signs
  • Leg ulcers

SEQUESTRATION

  • Splenomegaly - distended abdomen (fever, as hyposplenism, means a predisposition to infections)
  • Septic Shock as blood pools in organs

ANAEMIA

  • Jaundice
  • Conjunctival Pallor
  • Tachycardia
  • Maxillary hyperplasia (intramedullary hematopoiesis)
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8
Q

Identify appropriate investigations for sickle cell disease and interpret the results

A
  • FBC: normocytic Anaemia and Reticulocytosis (reticulocytosis not seen in aplastic crisis)
  • Peripheral Blood Smear
    • Sickled cell
    • Reticulocytes HIGH
    • Boat cells (seen in SCD)
    • Target cells (seen in haemoglobinopathies)
    • Howell-Jolly bodies (due to the hyposplenism)
  • Solubility test
    • In the presence of a reducing agent, oxyHb can be converted to deoxyHb (Fe3+ ➔ Fe2+)
    • In the presence of deoxyhaemoglobin S, the solution becomes turbid (OPAQUE) as Deoxy-HbS is insoluble
    • This does NOT differentiate between AS and SS
  • Cellulose-Acetate Electrophoresis/HPLC - DIAGNOSTIC
    • Electrophoresis or (HLPC) separates proteins according to charge
    • People with SCA (both defective beta-chains) have NO HbA,
    • Other forms of SCD (one normal beta) will have some HbA
    • HbA2 is present in all forms as it is formed from ⍺ and δ globin, not beta (HbA2 found in small proportions in all people)
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9
Q

Generate a management plan for sickle cell disease

A

ACUTE PAINFUL CRISIS

  • IV Analgesics (paracetamol & NSAIDs are first-line, opiates used in severe pain - given within 30 minutes of presentation
  • Correction of precipitant (e.g. giving Oxygen, Warming, fixing acidosis)
  • IV Fluid hydration
  • Empirical Antibiotics in ALL PEOPLE with fever (not always possible to rule out pneumonia)
  • Blood transfusion for life-threatening vaso-occlusive crises e.g. stroke or acute chest syndrome
  • Monitor spleen size with a view of Splenectomy

Management of chronic complications requires MDT approach and as much of the management as possible should take place in the community:

  • Reassure children with delayed growth and delayed puberty (and/or their parents/carers) that they will reach a normal adult height.
  • Refer people immediately if they present with an acute change in vision
  • Manage cerebrovascular events (refer for URGENT ASSESSMENT) if any new events
  • Reassure children with enuresis that it will resolve
  • Conservative management for priapism:
    • Keep hydrated
    • stay watm
    • Gentle exercise
  • If priapism persists >1hr go to hospital
  • First-line preventative therapy is alpha-adrenergic agonists and anti-androgens.

INFECTION PROPHYLAXIS (< 5 years old)

  • Penicillin (erythro if pen allergic)
  • Pneumococcal Vaccination (esp. against encapsulated bacteria) every 5 years in adults
  • Influenza
  • Men ACWY

ONGOING CRISES

  • HYDROXYUREA/HYDROXYCARBAMIDE
    • Increases levels of HbF and reduces the occurrence of painful crises
  • FOLATE SUPPLEMENTATION (only if folate deficient)
    • To stimulate erythropoiesis
  • REPEATED BLOOD TRANSFUSIONS
    • Repeated transfusions (with iron chelators) may be required in patients suffering from repeated crises
    • Exchange transfusions can rapidly reduce the number of HbS cells
  • BONE MARROW TRANSPLANT
    • Most effective in children with severe complications (e.g. recurrent strokes, ACS) → the only curative treatment
  • ADVICE
    • Avoid precipitating factors, good hygiene and nutrition, genetic counselling, prenatal screening - ANAESTHESIA is trigger
    • The importance of adherence to prophylactic antibiotics and the immunization schedule.
    • How to examine their child for pallor and an enlarging spleen.
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10
Q

Complications of SCD

A
  • Iron overload from repeated transfusions
  • Bilirubin (pigmented) gallstones
  • Avascular necrosis (hip or shoulder
  • Leg ulcer
  • Priapism
  • Dactylitis
  • Pulmonary HTN (ACS)
  • Renal abnormalities
  • Growth and development delay
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11
Q

Summarise the prognosis for patients with sickle cell disease

A
  • Most patients with sickle cell disease who manage their disease well will survive until around the age of 50 yrs
  • Mortality is usually the result of:
    • Pulmonary or neurological complications in ADULTS
    • Infection in CHILDREN
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12
Q

Diagnosis of Sickle Cell

A
  • Most cases of sickle cell disease are diagnosed as part of the National Newborn Screening Programme in the UK → people are rarely diagnosed in childhood/adulthood
    • Specifically the The Sickle Cell and Thalassaemia (SCT) Screening Programme
  • Infants do not usually manifest any signs and symptoms until they are 6 months old (they use HbF up to this point)
  • Milder forms of sickle cell disease may be diagnosed in adults with acute pain or on incidental blood testing.
  • Suspect an acute sickle cell crisis in a person with sickle cell disease who presents with a sudden onset of pain, infection, anaemia, or other symptoms, such as a stroke or priapism.
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13
Q

Symptoms in children over 6months

A
  • Dactylitis (painful swelling of the hands or feet as a result of vaso-occlusion)
  • Invasive infection.
  • Protuberant abdomen (due to an enlarged spleen), often with umbilical hernia.
  • Maxillary hypertrophy with overbite, due to extramedullary haematopoiesis, may also occur.
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14
Q

Investigations to order in an acute sickle crisis

A
  • FBC with differential (gives % of each WBC) and reticulocyte count.
  • U & E
  • LFTs
  • X-ray (chest/joints)
  • Cultures of blood/urine or other infection site
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15
Q

Who is sickle cell disease screening offered to:

A
  • Infants (around 5 days old)
  • Infants <1y who newly arrived in the uk
  • Pregnant women in high-prevalence areas
  • Biological fathers if the mother is a genetic carrier for sickle cell disease or thalassaemia.
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16
Q

What are the URGENT referral criteria in an acute crisis

A
  • Severe pain not controlled by simple analgesia or low dose opioids
  • Symptoms or signs of acute chest syndrome
  • Severe sepsis (T >38)
  • Dehydration
  • fever with no identified source associated with a sickle cell crisis needs bloods and cultures taken to look for the possible source of infection and early treatment as there is a higher risk of severe infections due to hyposplenism.
  • Acute hepatosplenomegaly over 24 hours, particularly in young children.
  • Marked increase in jaundice.
  • Any change in vision.
  • Haematuria
  • Priapism >2 hours

Haematology (9 decks)

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