Sickle Cell Trait

Sickle cell trait (haemoglobin AS) is the carrier state for the sickle cell gene, in which one beta globin gene carries the sickle (HbS) mutation and the other is normal. Carriers have about 35 to 45 percent HbS and are essentially healthy with normal life expectancy, but have specific risks under extreme conditions and can pass the gene to their children.

• Prevalence: up to 10 to 30 percent in parts of Kenya (the Lake Victoria and coastal regions), Uganda, Tanzania and West Africa; about 8 percent of people of African descent in North America; also in India, the Middle East and the Mediterranean.
• Protective against severe falciparum malaria (by about 90 percent for severe disease), which explains the high frequency.
• Inheritance: two carrier parents have a 25 percent chance with each pregnancy of a child with sickle cell disease (HbSS), 50 percent chance of a carrier child, and 25 percent chance of an unaffected child.
• Carrier plus another haemoglobin variant (HbC, beta thalassaemia) in a partner can produce compound heterozygous sickle disease (HbSC, HbS/beta thalassaemia).

• Usually completely asymptomatic with normal examination and normal blood counts (haemoglobin normal, MCV normal).
• Recognised complications (uncommon):
  • Painless haematuria from renal papillary necrosis, hyposthenuria (poor urine concentration), and rarely renal medullary carcinoma (young patients with haematuria and flank pain).
  • Splenic infarction at altitude (above 2000 to 3000 metres) with left upper quadrant pain; hypoxia during flying in unpressurised aircraft.
  • Exertional rhabdomyolysis and sudden collapse or death in extreme exertion, heat, dehydration, and altitude (military recruits, athletes).
  • Increased risk of venous thromboembolism, chronic kidney disease, and pulmonary embolism; hyphaema complications after eye injury.
  • Increased risk of urinary tract infection and bacteriuria in pregnancy.
• Sickle cell trait does not cause anaemia, painful crises, or stroke; unexplained anaemia or crises need another diagnosis.

• FBC (normal), blood film (normal; target cells occasionally), and sickling tests (the solubility test or sickle prep) are positive in trait and in disease, so they do not separate them.
• Definitive: haemoglobin electrophoresis, high performance liquid chromatography, or capillary electrophoresis shows HbA over HbS (HbS 30 to 45 percent, HbA 55 to 65 percent, HbA2 normal) with no HbF elevation.
• DNA analysis for beta globin gene when needed.
• Test the partner before or early in pregnancy, and test newborns where parents are carriers.
• Screen all pregnant women in endemic areas; combine with iron studies since iron deficiency lowers HbA2 and HbS levels and can confuse interpretation.
• Differentials: sickle cell disease (HbSS with anaemia, crises), HbC trait, HbS/beta thalassaemia, haemoglobin variants, and false positive solubility tests.

Reassure and counsel

• Sickle cell trait is not a disease, requires no treatment, no regular medication, and no restriction on normal life, work, school, or sport.
• Provide genetic counselling: explain inheritance, risks, and reproductive options (partner testing before pregnancy; prenatal diagnosis by chorionic villus sampling at 11 to 13 weeks or amniocentesis at 15 to 18 weeks; preimplantation genetic diagnosis).
• Carry a record of carrier status for medical care.

Prevent complications

• Hydration and avoid heat stress during exertion: drink fluids before, during and after exercise; gradual acclimatisation and conditioning; rest on the first sign of muscle pain, weakness, cramps, or dark urine; avoid extreme exertion at altitude; seek immediate care for exertional collapse.
• Altitude and aviation: commercial pressurised flights are safe; avoid unpressurised aircraft and rapid ascent above 3000 metres without acclimatisation.
• Haematuria: assess with urinalysis, renal ultrasound, and cystoscopy or CT if recurrent; manage with hydration, rest, and tranexamic acid 1 g orally three times daily for 5 to 7 days (caution in renal impairment); urgent imaging in young patients with persistent haematuria (renal medullary carcinoma).
• Annual urinalysis and blood pressure check; monitor renal function in older adults.
• Avoid unnecessary iron supplements unless iron deficiency is proven.

Pregnancy

• Routine antenatal care; screen urine for bacteriuria each trimester and treat (nitrofurantoin 100 mg modified release twice daily for 5 to 7 days in the first and second trimesters, or amoxicillin 500 mg three times daily for 5 days chosen by culture result); iron and folic acid supplementation 5 mg daily is not required unless deficiency.
• Test the partner; if the partner is a carrier, offer prenatal diagnosis.

Malaria

• Carriers are partially protected but not immune; use usual malaria prevention (insecticide treated nets) and treatment.

Surgery and anaesthesia

• Inform the anaesthetist; avoid hypoxia, hypothermia, dehydration, and prolonged tourniquet use; routine management otherwise.

Follow up

• No routine haematology follow up is needed; review if haematuria, renal symptoms, or unexplained anaemia develop.