Sickle Cell Disease

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IntroductionA 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 (which can also occur together in the same patient):.

  • Vaso-occlusive (painful/thrombotic crisis)
  • Anaemic

Clinical Presentation<6 months:

  • Usually do not show any feature of the disease due to HbF protection Late infancy (> 6 months – 2 years):
  • Persistent pallor/anaemia, jaundice, hepatosplenomegaly, and bone pains
    • extremities commonly.

Pre-school (2 – 5 years):

  • Persistent pallor/anaemia
  • Jaundice
  • Hepatosplenomegaly,
  • Bone pains,
  • Dactylitis – painful swelling of the digits,
  • Hand-foot syndrome – bilateral, painful, warm, non-pitting swelling of the dorsum of hands and feet
  • Sickle cell habitus – bossing and gnathopathy.

*Due to ischaemic necrosis of the bones of extremities. They are the earliest specific manifestations

School age (6 – 12 years):

  • Persistent pallor/anaemia
  • Jaundice
  • Hepatomegaly with or without splenomegaly (due to autosplenectomy)
  • Sickle cell habitus
    • Bossing (prominent facial and skull bones due to increased bone marrow activity)
    • Gnathopathy (overriding of maxillary bone over the mandible)
    • Asthenia (leaner and less weight)
    • Lower weight, height and BMI (though some have catch-up during adolescence)
    • Bone pain – usually backbones.

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)
  • Bone pain

Crises in SCD

  • Vaso Occlusive Crises( VOC):
    • Bone pain crisis
    • Abdominal pain crisis
    • Acute hepatopathy
    • Acute chest syndrome
    • Priapism
    • 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 and Renal tubular acidosis
  • Cardiovascular system complications
    • Cardiomegaly – due to functional adaptation to chronic anaemia
    • CCF
    • Cor pulmonale
  • 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, Haemophilus 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

  • FBC and ESR
  • Total leukocyte count, differential leukocyte count (Neutrophils including bands, lymphocytes, monocytes, basophils, eosinophils)
  • 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 micro albuminuria
    • Echocardiography detects pulmonary hypertension
    • Pulse oximetry

Treatment goals

  • Maintain (or restore) a steady state of health
  • Prevent and treat complications
  • Provide accurate diagnosis, relevant health education and genetic counseling to patients, relatives and heterozygotes
  • Improve quality of live
  • Provide a positive self-image in affected persons
  • Strategies:
  • Counselling 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:
    • Blood transfusion (especially red cell transfusion)

Drug treatment

Steady state (when patient is well with no complaints)

  • Proguanil
    • Infants 25 mg orally daily
    • 1 - 4 years 50 mg orally daily
    • 5 - 8 years 100 mg orally daily
    • 9 - 14 years 150 mg orally daily
  • Plus
    • Folic acid 5 mg orally daily
  • Plus
    • Other vitamins as may be required
    • Omega 3 fatty acids
    • K-thiocyanate
    • Penicillin for children
      • >2 months - 3 years: 125 mg orally 12 hourly
      • Over 3 years: 250 mg orally 12 hourly
      • Hydroxyurea 15 mg/kg and build it up to maximum 35 mg/kg by weekly increment.

Pain crisis:

Mild pain:

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

Or

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

Moderate to severe pain:

  • Diclofenac sodium 2 mg/kg/24 hours intramuscularly in 2 - 4 divided doses

Or

  • Pentazocine:
    • Adult and child> 14 years 30 mg/dose 4 - 6 hourly intramuscularly
    • Child < 14 years, 15 mg/dose 6 - 8 hourly intramuscularly or intravenously

Or

    • Dihydrocodeine (DF118) orally 0.5 - 1 mg/kg 8-12 hourly

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)

Others

  • 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

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

Notable Adverse Drug Reactions, Contraindications and Caution

  • 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 on an empty stomach.