Sickle Cell Disease in Children

Introduction

Sickle cell disease is a group of inherited red blood cell disorders with one abnormal haemoglobin called Haemoglobin S and another that is also abnormal in the rbc.
Haemoblobin molecule is unusually sensitivity to low oxygen tension making it to denature affecting its shape to sickle and its oxygen carrying capacity. If the other abnormal haemoglobin is another S, the condition is called sickle cell anaemia, the commonest variant of sickle cell disorders.
Manifestations which vary with age and may have intermittent episodic events called crises tend to occur.
The two broad forms are :

  1. vaso-occlusive (painful/ thrombotic crisis)
  2. Anaemic

Two of these can also occur together in the same patient.

Clinical Presentation

<6 months

  • Usually do not show any feature of the disease due to HbF protection

Late infancy (> 6mths – 2yrs)

  • Persistent pallor/anaemia, jaundice, hepatosplenomegaly, and bone pains -extremities commonly.

Pre-school (25 years)

  • Persistent pallor/anaemia, jaundice,
    hepatosplenomegaly, bone pains, dactilytis  (painful swelling of the digits, and hand)
    foot syndrome – bilateral, painful, warm, non-pitting swelling of the dorsa of hands and feet, sickle cell habitus – bossing and gnathopathy.
  • Due to ischaemic necrosis of the bones of extremities. They are earliest specific manifestation

School age (6-12 years)

  • Persistent pallor/anaemia, jaundice,
    hepatomegaly + splenomegaly (due to autosplenectomy), sickle cell habitus – bossing (prominent facial and skull bones due to increased bone marrow activity); gnathopathy (overridding of maxillary bone over the mandible); asthenia (leaner and less weight) – lower weight, height and BMI (though some have catch-up during adolescence) and bone pain – usually back bones.

Adolescents

  • Persistent pallor/anaemia, jaundice,
    hepatomegaly + splenomegaly, sickle cell habitus, delayed sexual development in both sexes (mean menarcheal age 15.5 years as against 13.4 years in AA girls) and bone pain.

Crises in SCD

1. Vaso Occlusive Crises (VOC)

  • Bone pain crisis, abdominal pain crisis, acute hepatopathy, acute chest syndrome, priapism and cerebrovascular accident (CVA).

Precipitating factors to VOC

  • Fever, infection, physical exertion, extremes of weather and emotional disturbance

Anaemic Crises

  • Aplastic crisis – due to parvovirus B19
  • Hyperhaemolytic crisis – precipitated by malaria and bacterial infection
  • Sequestration crisis – trapping of significant proportion of rbc in the spleen
  • Megaloblastic changes – folic acid
    deficiency

Complications of SCD

Occur in almost all the body organs.

Musculoskeletal system complications

  • Osteomyelitis – commonly staph aureus
  • Avascular necrosis of hip or shoulder joints
  • Pathological fracture
  • Digital clubbing
  • Chronic leg ulcer – common in adolescents, affects the skin around the malleoli, heals slowly and recurs.
  • Kyphosis
  • Scoliosis
  • Kyphoscoliosis

Hepatobiliary system complications

  • Hepatomegaly
  • Hepatic coma – rare
  • Haemosiderosis – transfusion associated
  • Cholelithiasis- uncommon in Africa

Genito-urinary system complications

  • Hyposthenuria, polyuria, nocturia, enuresis due to impaired urinary concentrating ability.
  • Begins by 4 – 5years
  • Haematuria usually from the left kidney
  • Proteinuria – early manifestation of
    sickle cell nephropathy
  • Bacteriuria affects 22% of febrile SCD children
  • Pyelonephritis
  • Renal tubular acidosis

Cardiovascular system complications

  • Cardiomegaly due to functional adaptation to chronic anaemia
  • CCF
  • Cor pulmonare

Respiratory system complications

  • Pulmonary hypertension
  • Hypoxaemia – hallmark of
    pulmonary function abnormality in SCD
  • Reduced lung volume – Due to frequent pneumonia and reduced thoracic size

Central nervous system complications

  • CVA
  • Seizures
  • Sensorineural hearing loss
  • Ocular lesions – anterior and
  • posterior chamber lesions
  • Susceptibility to infection
  • Sepsis and other bacterial infections especially pneumonia, H. influenza,  salmonella due to
    • Altered splenic function
    • Functional asplenia
    • Defective alternate pathway of complement activation
    • Elevated serum iron
    • Deranged pulmonary alveolar macrophage function from chronic hypoxia
  • Impaired psychosocial function
  • Physical, skeletal and sexual maturation problems
  • Societal attitude /discrimination
  • Frequent ill-health and hospitalization
  • School absenteeism
  • Role limitations
  • Loss of job
  • Persistent jaundice
  • Neurocognitive impairment
  • Academic performance
  • Parents and siblings psychological problems

Investigations

  • Full blood count (FBC)
  • Haemoglobin, PCV, RBC count
  • Total leukocyte count, differential leukocyte count (Neutrophils including bands, lymphocytes, monocytes, basophils, eosinophils)
  • Platelet count
  • Erythrocyte sedimentation rate (ESR)
  • Red blood cell indices (MCV, MCHC, MCH)
  • Blood film may show sickled and other abnormally shaped red cells, malaria parasites
  • Reticulocyte count
  • Sickling test using 2% sodium methabisulphite as a deoxygenating agent
  • Solubility test using sodium dithionate as buffer
  • Haemoglobin electrophoresis using
    cellulose acetate paper at pH 8.4
    (alkaline) or citrate agar gel at pH 5.6 (acidic). This detects the variant
    haemoglobin bands
  • High performance liquid chromatography (HPLC) for Haemoglobin quantitation
  • Serum electrolytes, urea and creatinine
  • Liver function test:
    • serum bilirubin-total and conjugated transaminases
    • alkaline phosphatase
    • serum albumin
    • prothrombin time.
  • Urinalysis, microscopy, culture and
    sensitivity
  • Stool microscopy for ova and parasites, occult blood
  • Sputum M/C/S, acid fast bacilli
  • Chest X-Ray
  • Ultrasound scan
  • Abdominal ultrasound
  • Trans cranial Doppler ultrasound (TCD) detects those at increased risk of cerebrovascular accident (CVA)
  • Magnetic Resonance Imaging (MRI)
    detects brain micro infarcts
  • Organ dysfunction screen:
    • kidney: urinalysis, 24-hour urine protein quantitation, renal ultrasound, measurement of GFR, screen for microalbuminuria
  • echocardiography detects pulmonary hypertension
  • Pulse oximetry

Treatment

Objectives:

  • Maintain (or restore) a steady state of health
  • Prevent and treat complications
  • Provide accurate diagnosis, relevant health education and genetic counselling to patients, relatives and heterozygotes
  • Improve quality of live
  • Provide a positive self-image in
    affected persons

Strategies:

  • Counseling and health education
  • Encouraging membership of support groups
  • Providing infection prophylaxis
    • Anti-malarial
    • Anti-pneumococcal
    • Hepatitis B, pneumococcal, H influenza and other childhood vaccines
  • Providing folate supplementation
  • Avoiding pain-inducing conditions
  • Providing prompt treatment of symptoms
  • Advising on contraception
  • Supervising pregnancy/Labour
  • Providing regular health checks
  • Limiting family size

Non-drug treatment:

  • Balanced diet- encourage adequate intake of vegetables and fruits
  • Adequate fluid intake (at least 3 litres per/24 hours or 1.5L/m²/24 hours)
  • Avoidance of Pain-inducing conditions
  • Strenuous exertion or stress
  • Dehydration
  • Sudden exposure to extremes of temperature
  • Infections e.g. malaria (encourage use of insecticide treated nets)
  • Emotional stress

Adjunct treatment:

Drug treatment:

Steady state (when patient is well with no complaints)

Proguanil

  • Infants: 25mg orally daily
  • 1-4 years: 50mg orally daily
  • 5-8 years: 100mg orally daily
  • 9-14 years: 150mg orally daily

Plus

  • Folic acid 5mg orally daily

Plus

Other vitamins as may be required

  • Omega 3 fatty acids
  • K-thiocyanate

Penicillin for children

  • >2 months-3 years, 125mg orally 12 hourly
  • Over 3 years, 250mg orally 12 hourly

Pain crisis:

Mild pain
Paracetamol:

  • Child 10mg/kg/dose orally 4-6 hourly (max. 4 doses/24 hours)

OR

Ibuprofen:

  • child 5-10mg/kg/dose orally 6-8 hourly (max. 40-60mg/kg/24 hours)

Moderate to severe pain
Diclofenac sodium:

  • child 2mg/kg/24 hours intramuscularly in 2 – 4 divided doses

OR

Pentazocin:

  • adult and child> 14 years: 30mg/dose 4-6 hourly intramuscularly

OR

Dihydrocodeine (DF118) orally

OR

Morphine,

  • infants and children, 0.1-0.2mg/ kg/ dose 2-4 hourly IM, IV, SC or 0.2-0.5mg /kg/dose orally 4-6 hourly
  • Adolescents, 3-4 mg /dose (as necessary)

Anti-malarial:

  • Artemisinin-based combination
    therapy (ACT): see section on malaria
  • Detection and treatment of
    precipitating factors e.g. malaria,
    sepsis, dehydration etc.

Supportive measures:

  • Counseling and health education
  • Membership of support groups
  • Regular health checks

Notable adverse drug reactions, cautions and contra-indications:

  • Paracetamol should be used with caution in patients with hepatic impairment
  • Opioid analgesics cause varying
    degrees of respiratory depression
    and hypotension. They should be
    avoided when raised intra-cranial pressure is suspected
  • NSAIDS can cause abdominal pain,
    gastrointestinal bleeding, ulceration
    and perforation. It should not be
    taken in an empty stomach