Introduction to Sickle Cell Disease
Sickle cell disease is a group of conditions with pathological
processes resulting from the presence of
Haemoglobin S Usually inherited from the parents who have themselves inherited haemoglobin S.
The principal genotypes include:
- Homozygous sickle cell disease (SS)
- Sickle cell-haemoglobin C disease (SC)
- Sickle cell-B thalassaemia (SB thal)
- Sickle cell-B+ thalassaemia Type I (SB+thal. Type I)
- Sickle cell-B+thalassaemia. Type II. (SB+thal Type II)
- Sickle cell-B+thalassaemia. Type III. (SB+thal. Type III)
Sickle cell trait
Inheritance of one normal gene controlling formation of B Haemoglobin (HbA), and a sickle gene (HbS).
Total haemoglobin A is more than haemoglobin S Normal haemoglobin F
Sickle cell disease
Sickle cell disease occur as a result of inheritance of two abnormal allelemorphic genes controlling formation of B chains of haemoglobin, at least one of which is the sickle gene.
Polymerization of the sickle haemoglobin may lead to vaso-occlusion
Pathophysiology of Sickle Cell Disease
Red cells have reduced deformability and easily adhere to vascular endothelium, increasing the potential for decreased blood flow and vascular obstruction.
Abnormalities in coagulation, leucocytes, vascular endothelium, and damage to the membranes of red cells contribute to sickling Haemolytic anaemia and vasculopathy are the result of the various pathophysiologic processes.
Organ damage is on-going and is often silent until far advanced.
The course of the disease is punctuated by episodes of pain
Clinical features of Sickle Cell Disease
Vary widely from one patient to another:
- Persistent anaemia/pallor
- growth retardation (variable);
- Jaundice (variable);
- Bone pains (recurrent)
- Prominent facial bones due to increased bone marrow activity
- Leaner body build and less weight (on average)
- Some fingers are shortened as a result of infarction (destruction due to blockage of blood supply)
- Hand-foot syndrome (painful and swollen hands and feet) in childhood
- Life span on average shorter than normal
- Sexual development is delayed in both sexes:
- menarche occurs at a mean age of 15.5 years (range 12-20 years) compared to non-sicklers (mean 13.2years)
- Impotence can occur from prolonged priapism
- High foetal loss in pregnancy
Sickle cell crises
Patient has acute symptoms/signs attributable directly to sickle cell disease
Two main types:
- Pain (vaso-occlusive) crisis
- Anaemia crisis
1. Vaso-occlusive crises
- Painful
- Tender, swollen bones
- Acute chest syndrome
- Acute hepatopathy
- Priapism
- Painless Haematuria
- Cerebrovascular disease (accident) in descending order of prevalence
- Thrombotic stroke Seizures
- Haemorrhage
- Retinopathy (commonest in SC patients)
2. Anaemic crises
- Acute splenic (or hepatic) sequestration
- Hyper-haemolytic (e.g. precipitated by malaria
- Hypoplastic (due to infection or renal failure)
- Aplastic (e.g. due to epidemic parvo virus B19)
- Megaloblastic (folic acid deficiency)
Differential diagnoses
- Connective tissue disorders e.g. rheumatoid arthritis.
- Liver disease
- Other causes of failure to thrive
Complications of Sickle Cell Disease
- Kidneys:
- Hyposthenuria (reduced ability to concentrate urine/conserve body fluids)
- Haematuria
- Albuminuria
- Reduced kidney function
- Leg ulcers:
- Occur around ankles.
- Heal slowly and tend to recur
- Bones and Joints
- Osteomyelitis
- Avascular necrosis
- These may cause:
- Hip pain
- Limping gait
- Kyphoscoliosis when necrosis affects spinal vertebral bones
- Infections:
- Salmonella osteomyelitis
- Pneumococcal pneumonia
- Pneumoccoccal meningitis (rare in adolescents and adults)
- Tonsillitis and pharyngitis
- Brain and nerves:
- Strokes, seizures (not common in adults)
- Meningitis (not common in adults)
- Cerebral haemorrhage
- Mental neuropathy (rare)
- Cardiovascular/respiratory:
-
- Heart failure
- Pulmonary hypertension
- Acute chest syndrome
Investigations
- Full Blood Count (haemoglobin, haematocrit, total leucocyte count and differential counts, platelet counts)
- Erythrocyte sedimentation rate
- Red cell indices (MCH, MCHC, MCV)
- Reticulocyte count
- Sickling tests: solubility test; metabisulphite test
- Haemoglobin electrophoresis
- Using cellulose acetate paper at pH 8.4
- (alkaline) or citrate agar gel at pH 5.6 (acidic)
- Serum Electrolytes, Urea and Creatinine
- Liver function tests (transaminases, bilirubin, serum albumin, alkaline phosphatase and prothrombin time)
- Others as may be indicated:
- Urinalysis; microscopy, culture and sensitivity:
- Sputum
- Acid Fast Bacilli
- Microscopy, culture and sensitivity
- Stool:
- Ova and parasites
- Occult blood
- Ultra sound scan:
- Abdominal ultrasound scan
- Transcranial Doppler ultrasonography Chest radiograph
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 life
- Provide a positive self-image in affected persons
Treatment strategies
Counselling and health education
- Encouraging membership of support groups
- Providing infection prophylaxis (antimalarial; anti-pneumococcal, hepatitis B virus 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
- Adequate fluid intake (at least 3 litres/24 hours)
- Avoidance of pain-inducing conditions
- Strenous physical exertion or stress
- Dehydration
- Sudden exposure to extremes of temperature
- Infections e.g. malaria
- Emotional stress
Adjunct treatment
- Blood transfusion (especially red cell transfusion)
- Anti-pneumococcal vaccine
Drug treatment for Sickle Cell Disease
1. In steady state (when patient is well with no complaints):
Proguanil
- Adult:200 mg orally daily
- Child: under 1 year 25 mg daily; 1-4 years 50 mg; 5-8 years 100 mg: 9-14 years 150 mg orally daily
Plus:
- Folic acid 5 mg orally daily
2. In pain crises.
A. Mild pain
Paracetamol
- Adult: 1 g, every 4-6 hours to a maximum of 4g daily
- Child: 1-5 years 120-250 mg; 6-12 years 250-500 mg; 12-18 years 500 mg every 4-6 hours (maximum 4 doses in 24 hours)
Or:
- Aspirin (acetylsalicylic acid) 600 mg orally every 8 hours daily
- Not recommended for children under 16 years
Or:
- Ibuprofen 200 mg every 8 hours daily (or other non-steroidal anti-inflammatory drugs)
- Not recommended for children under 16 years
B. Moderate-to-severe painful crises
Parenteral therapy:
Diclofenac sodium
- Adult: 75 mg or 100 mg intramuscularly (as necessary)
- Not recommended for children
Oral therapy:
Paracetamol
- Child: 1-5 years 20mg/kg every 6 hours (maximum 90 mg/kg daily in divided doses) for 48 hours or longer if necessary and if adverse effects are ruled out Then: 15 mg/kg every 6 hours (maintenance) 6 – 12 years: 20 mg/kg (maximum 1 g) hourly (maximum 90 mg/kg daily in divided doses, not to exceed 4 g for 48 hours or longer if necessary and if adverse effects are ruled out
Then:
15 mg/kg every 6 hours (maximum 4g daily) 12-18 years: 500 mg-1g every 4-6 hours (maximum 4 doses in 24 hours).
Diclofenac potassium 50 mg every 12 hours daily
Or:
Diclofenac sodium 100 mg once daily
Or:
Morphine 15 mg every 8-12 hours daily
Antimalarials
Artemisinin-based combination therapy
Supportive measures
- Counselling and health education
- Membership of support group
- Regular health checks
- Supportive measures
Notable adverse drug reactions, caution and contraindications
- 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 intracranial pressure is suspected to be raised
Prevention
- Advice on the risks involved in marriages between carriers, and between sicklers
- Anti-pneumococcal vaccine (once every 5 years)