SICKLE CELL DISEASE

Sickle cell disease (SCD) is a genetic haemoglobin disorder in which red blood cells which carry oxygen around the body change shape from a smooth doughnut shape into a crescent or half-moon shape. It is sometimes called Sickle Cell Anaemia (SCA).

Cause

  • It is caused by a defect in beta chains where a given amino acid is replaced by another (Substitution of valine for glutamic acid) at position 6 of the chain. This change creates abnormal haemoglobin called HbS.

Clinical features

  • Symptoms usually appear from age of 3 to 6 months: anaemia, dactylitis (swelling of fingers), lobar pneumonia, recurrent severe bacterial infections. This results from the reduction of the foetal haemoglobin F (HbF), and increase in HbS in the blood
  • Chronic anaemia: Hb 6–9 g/dl with episodes of acute worsening, which can be due to
  • Aplastic crisis: sudden transient arrest of blood cells production in the bone marrow (low Hb and low
    reticulocyes), often due to ParvoB19 virus infection)
  • Splenic sequestration: pooling of large amounts of red blood cells in the spleen with painful and rapidly enlarging spleen, decreasing haemoglobin with high reticulocyte count
  • Acute vaso-occlusive phenomenon (occlusion of blood vessels) causing:
    • Painful crisis (acute, intense) at the back, chest, limbs, abdomen. In children <2 years, pain and swelling of hands and feet.
    • Stroke: hemiplegia, altered consciousness, seizures
    • Acute chest syndrome: fever, chest pain, difficulty in breathing, low oxygen level, cough, wheezing
    • Acute abdomen or mesenteric crisis (“intestinal crisis”): abdominal pain and distension, reduced or absent bowel sounds, pallor, fever, Abdominal X-ray may show dilated bowel loops. Anaemia, high reticulocyte count, high CRP
    • Renal infarction, bone infarction and necrosis, priapism
  • Chronic organ damage due to anaemia and
    vasocclusive phenomenon:

    • Hyposplenia (spleen becomes so damaged that is not functional anymore or has to be removed because of
      splenic sequestration)
    • Pulmonary hypertension, asthma
    • Chronic renal and hepatic disease, gallbladder stones
    • Osteoporosis, retinopathy
    • Chronic leg ulcers
  • Infections favoured by hyposplenism and low tissue perfusion
    • Osteomyelitis, pneumonia, septicaemia

Investigations

  • Family history of sickle cell disease
  • Full blood count & peripeharl film comment
  • Screening tests for sickling (not fully reliable)
  • Haemoglobin electrophoresis (confirms diagnosis)
  • Chest radiography (for Acute Chest Syndrome)
  • Abdominal ultrasound
  • Urinalysis
  • Liver and renal function tests

Management

Chronic management

General measures

  • Regular follow up and education of patients and families
  • Always keep well-hydrated
  • Give folic acid 5 mg daily for life
  • Promptly assess, and treat any fever with antibiotics until source of fever is identified
  • Ensure complete immunisation using the UNEPI programme, which includes the pneumococcal
    vaccine for all infants

    • Plus, if available, immunisation against meningococcus (to be given in regions within the
      meningococal belt) and influenza
  • Prophylactic penicillin V (up to 5 years of age)
    Child 3 months-3 years: penicillin V 125 mg every 12 hours
    Child 3-5 years: penicillin V 250 mg every 12 hours
  • Malaria prophylaxis with monthly sulphadoxinepirimetamine(SP)
    Child 2-5 years: ½ tab monthly
    Child 5-10 years: 1 tab monthly
    Child 10-15 years: 2 tabs monthly
    Child >15 years: 3 tablets monthly
    For those with sulphur allergy consider use oferythromycin 250 mg every 12 hours

Refer to a specialised treatment centre for specialised management, especially of uncontrolled symptoms

  • Hydroxyurea starting dose 20 mg/kg

Indications for hydroxyurea

  • Frequent crises: >5 crises in a year
  • Patients with abnormal Transcranial Doppler (TCD) Ultrasonography velocity >200 cm/s
  • Acute Chest Syndrome
  • Stroke

Note: However, the decision to give a patient hydroxyurea should be done by a senior health worker after full laboratory investigation of the patient including:

  • Complete blood count
  • Renal function tests
  • Liver function tests

Management of acute complications

Painful crisis – home management (mild to moderate pain)

  • Oral hydration
  • Warm compresses (not cold)
  • Paracetamol 1 g every 8 hours
    Child: 10-15 mg/kg 6-8 hourly
  • And/or ibuprofen 400-600 mg every 6-8 hours
    Child: 5-10 mg/kg 8 hourly
  • And/or diclofenac 50 mg 8 hourly
    Children only >9 years and >35 kg: 2 mg/kg in 3 divided doses

If pain not controlled, add:

  • Codeine 30-60 mg every 6 hours (only in patients >12 years)
  • Or tramadol 50-100 mg every 6-8 hours (only in patients >12 years)
  • Or Oral morphine at 0.2-0.4 mg/kg every 4 hours and re-assess pain level


If pain still not controlled, refer to hospital

Painful crisis – hospital management (severe pain)

  • IV fluids for rehydration
  • Oxygen
  • Assess for malaria and infection
  • Injectable diclofenac
    Child: 1 mg/kg IM 8 hourly
    Adult: 50-75 mg IM 8 hourly
  • Morphine oral (see section 13.1.2)
    Child and Adult: 0.3-0.6 mg/kg per dose and reassess
  • Or Morphine IV
    Child: 0.1-0.2 mg/kg per dose
    Adult: 5-10 mg dose and re-assess

Note

  • Use of laxative: bisacodyl 2.5 mg to 5 mg orally to prevent constipation due to morphine


Acute anaemia (acute splenic sequestration, aplastic crisis)

  • Transfuse
  • IV fluids if necessary
  • Investigate and treat malaria, and infections
  • Avoid splenectomy in acute sequestration (high mortality)

Acute Chest syndrome

  • Restricted IV fluids use, always use calculated required amounts of IV fluids. NB: limit in cases of pulmonary oedema
  • Oxygen therapy
  • Pain management as above
  • Salbutamol inhaler (2-4 puffs prn) or nebulisation 5 mg (2.5 mg for children <5 years)
  • Ceftriaxone 1-2 g once daily for 7-10 days
    Child: 80-100 mg/kg once daily
  • Plus erythromicin 500 mg every 6 hours for 7-10 days
    Child: 5-10 mg/kg every 6 hours
  • Transfuse if no improvement, and/or Hb falls <9 g/dL

Stroke

  • Oxygen to mantain SpO2 >94%
  • Tranfuse if Hb <9 g/dl
  • IV fluids
  • Refer for neuroimaging and advanced management

Acute Abdomen/Mesenteric crisis

  • IV fluids
  • Nil by mouth
  • NGT tube on free drainage
  • Antibiotics
  • Ceftriaxone 1-2 g once daily for 7-10 days
  • Child: 80 mg/kg once daily
  • Plus metronidazole 500 mg IV every 8 hours for 7-10 days
  • Child: 10 mg/kg IV every 8 hours
  • Red cell transfusion
    • Plain abdominal X-ray to rule out obstruction or stool impaction
  • Surgical review

Infections

  • Prompt assessment and treatment of cause (osteomyelitis, pneumonia, cellulitis, etc.)
  • Treat according to cause. If no localising focal symptoms, and no malaria, give:
  • Ceftriaxone 1-2 g once daily for 7-10 days
    Child: 80 mg/kg once daily


If osteomyelitis or septic arthritis

  • Or Cloxacillin 500 mg 6 hourly IV or orally
  • Child: 50 mg/kg 6 hourly for at least 21 days
  • or Ciprofloxacin 500 mg 12 hourly for at least 21 days
    • In child: Ceftriaxone 50 mg/kg IV once a day for at least 21 days

Indications for blood transfusion<

  • Acute exacerbation of baseline anaemia:
    • Hyperhaemolysis
    • Hepatic sequestration
    • Splenic sequestration
    • Aplastic crisis
  • Severe vaso-occlusive events:
    • Stroke
    • Acute chest syndrome
    • Severe infection
    • Multi-organ failure
  • Preparation for procedures:
    • Surgery
    • Radiography with ionic contrast
    • General anaesthesia

Prevention/health education

  • Patient, family and community education
  • Periodic comprehensive evaluations, and other diseasespecific health maintenance services
  • Timely and appropriate treatment of acute illness
  • Genetic counseling (for couples planning to have children)
  • Antenatal screening
  • Early recognition/screening of children with low Hb
  • Vaccination (pneumococcal vaccine, H-influenza vaccine, Hepatitis B vaccine evaluation)
  • Antibiotic (oral penicillin twice a day), and antimalarial chemoprophylaxis