Sickle Cell Disease - Infection management/ prophylaxis

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Introduction

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+ Type II. (SB+thal Type II)
• Sickle cell-B+ 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

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

• 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 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

• 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 13.2 years)
• 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

Vaso-occlusive crises

• Painful, tender, swollen bones
• Acute hepatopathy
• Acute chest syndrome
• Priapism
• Painless haematuria
• Cerebrovascular disease (accident) - in descending order of prevalence
  • Thrombotic stroke
  • Seizures
  • Haemorrhage
  • Retinopathy (commonest in SC patients)

Anaemic crises

• Acute splenic (or hepatic) sequestration
• Hyper-haemolytic (e.g. precipitated by malaria)
• Megaloblastic (folic acid deficiency)
• Hypoplastic (due to infection or renal failure)
• Aplastic (e.g. due to epidemic parvo virus B19)

Differential diagnoses

• Connective tissue disorders g. rheumatoid arthritis
• Liver disease
• Other causes of failure to thrive

ComplicationsKidneys:

• Hyposthenuria (reduced ability to concentrate urine/conserve body fluids)
• Haematuria
• Albuminuria
• Reduced kidney function

Leg ulcers:

• Occur around the 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
• Pneumococcal 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 and respiratory:

• Heart failure
• Pulmonary hypertension
• Acute chest syndrome​

Investigations

• FBC and ESR; 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 goals

• 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

Adjunct treatment

• Blood transfusion (especially red cell transfusion)
• Anti-pneumococcal vaccine

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 g. malaria
• Emotional stress

Drug treatment

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 Plus
• Multivitamin 1 every 8 hours
• Omega-3 1 every 12 hours Pain crises

Mild pain

• Paracetamol
• Adult: 1 g every 4 - 6 hours to a maximum of 4 g 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
• Adult: 200 mg every 8 hours daily (or other non-steroidal anti- inflammatory drugs)
• Child: 10 mg/kg/dose every 8 hours Moderate-to-severe painful crises Parenteral therapy:
• Diclofenac sodium
• Adult: 75 mg or 100 mg intramuscularly (as necessary)
• Not recommended for children
• Pentazocine
• Adult:
• Child: Pentazocine 5-1mg/kg every 6-8 hours Oral therapy:
• Paracetamol
• Child: 1 -5 years 20 mg/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) 6 hourly (maximum 90 mg/kg

Then:

daily in divided doses, not to exceed 4 g for 48 hours or longer if necessary and if adverse effects are ruled out

• 15 mg/kg every 6 hours (maximum 4 g daily)
• 12 - 18 years: 500 mg - 1g every 4 - 6 hours (maximum 4 doses in 24 hours)
• Diclofenac potassium 50 mg every 12 hours Or:
• Diclofenac sodium 100 mg once daily Or:
• Dihydrocodeine 1-2 mg/kg every 8 hours Or:

Morphine 15 mg every 8 - 12 hours daily Antimalarials

Artemisinin-based combination therapy (see section on malaria) Supportive Measures

• Counselling and health education
• Membership of support group
• Regular health checks Definitive treatment:
• Stem cell transplantation and Gene therapy

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 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)