Makindo Medical Notes

Inform haematology immediately if a known HbSS/SC or equivalent patient is admitted. In sickle cell disease (SCD), red blood cells take on a sickle-like shape under conditions of deoxygenation, leading to various complications.

About Sickle Cell Disease

• Sickle Cell Disease (SCD) is a chronic haemolytic anaemia primarily affecting individuals of Afro-Caribbean origin.
• The most common and severe form is homozygous sickle cell anaemia (HbSS), which accounts for 70% of cases in the UK.
• Compound heterozygotes, such as those with HbS and HbC (SC disease), form a significant portion of the remainder. Other variants can lead to milder or more severe sickling disorders.
• Many patients carry a haemoglobinopathy card for quick identification in emergency situations.
• Heterozygous carriers (HbAS or sickle cell trait) generally do not experience symptoms but have some protection against malaria.

Aetiology

• A point mutation results in the substitution of valine for glutamic acid at the 6th position of the beta-globin chain.
• This alteration causes HbSS to be less soluble as valine is hydrophobic, which leads to the polymerisation of haemoglobin at low oxygen levels.
• Haemoglobin electrophoresis is used to diagnose sickle cell disease and trait.
• At low oxygen tensions, HbS polymerises inside the red blood cells, causing them to adopt a sickle shape and leading to various complications.

Sickling Precipitants

• Deoxygenation or exposure to high altitudes.
• Dehydration or fluid imbalance.
• Infections or fever, rapid temperature changes.
• Pregnancy and other stress factors can precipitate crises, often creating a vicious cycle where sickling leads to more sickling.

Types of Haemoglobinopathy

• HbSS (Sickle Cell Anaemia): The most severe form, with no normal beta-globin chains (no HbA). Patients are usually anaemic.
• HbSC Disease: Compound heterozygotes with HbS from one parent and HbC from the other. It is a milder form, though crises can still occur, and haemoglobin levels may be normal.
• HbS/β-thalassaemia: HbS from one parent and beta-thalassaemia from the other. Symptoms resemble sickle cell anaemia.
• Sickle Cell Trait (HbAS): A heterozygous state with HbS from one parent, which is clinically silent but can be passed to offspring.

Clinical Presentation

• Initial Assessment: Evaluate the type of sickle cell crisis and screen for medical complications that require immediate intervention.
• Infections: Look for fever or dehydration as common precipitants of crises.
• Acute Chest Syndrome: Fever, dyspnoea, chest pain, hypoxia, and falling Hb with respiratory rate >25/min. Consider oxygen therapy and investigate potential chest infections.
• Severe Anaemia: Suspect aplastic crisis, particularly following viral infections.
• Cholecystitis: Evaluate for obstructive jaundice due to gallstones, a common complication.
• Splenic Sequestration: Rapid enlargement of the spleen with associated hypovolaemia.
• Neurological Signs: Cerebral sickling can cause strokes due to small and large vessel infarcts.
• Priapism: Painful, prolonged erection due to sickling in the corpus cavernosum.

Complications

• Haemolytic anaemia, recurrent sickling crises.
• Acute chest syndrome, often requiring ICU care.
• Salmonella osteomyelitis, pneumococcal infection due to autosplenectomy.
• Avascular necrosis of the hips and other joints.
• Renal papillary necrosis, leading to loin pain, haematuria, and urinary obstruction.
• Bone pain from sickling or avascular necrosis of the femoral head, often seen as dactylitis (painful swelling in hands/feet).
• Splenic infarction, leading to autosplenectomy.
• Priapism, requiring urgent intervention to prevent long-term damage.
• Renal failure, pulmonary fibrosis, hepatosplenomegaly, and skin ulcers.
• Recurrent infections: Patients require vaccinations for pneumococcus and Haemophilus influenzae.

Investigations

• FBC: Anaemia and elevated WCC suggest infection. High reticulocyte count reflects bone marrow response.
• Sepsis Screen: Blood and urine cultures to rule out infections.
• Oxygen Saturation and ABG: Hypoxia indicates acute chest syndrome or possible PE.
• ECG: Rule out myocardial ischaemia in chest pain cases.
• U&E, LFT, LDH, Bilirubin, Haptoglobin: To evaluate for dehydration, haemolysis, and organ dysfunction.
• CXR: Look for consolidation (acute chest syndrome) or pleural effusion.
• CTPA: Consider if pulmonary embolism is suspected.
• X-ray: For painful bones or fever to rule out osteomyelitis.
• CT/MRI Brain: For acute neurological symptoms to evaluate for stroke or cerebral sickling.

Management of Acute Sickling Crisis

• Fluid Replacement: IV normal saline is essential to maintain hydration. Oral hydration (>60 mL/kg/24 hrs) may suffice if the patient can drink adequately, otherwise consider NG fluids.
• Pain Management: Opiates, such as morphine, should be administered within 30 minutes of presentation. Titrate to effect, monitor respiratory status closely, and use laxatives to prevent constipation.
• NSAIDs: Consider Diclofenac or Ibuprofen as adjunctive therapy for pain management, in addition to Paracetamol.
• Antibiotics: Start empirically if the patient is febrile or shows signs of infection. Augmentin is commonly used unless the patient is penicillin-allergic.
• Anxiolytics: Haloperidol 1-3 mg oral or IM can be used for agitation or severe anxiety.
• Oxygen Therapy: Maintain O₂ saturation >95%. Patients in sickling crisis should receive 35% oxygen or higher if needed.
• Exchange Transfusion: Consider in severe cases such as acute chest syndrome, cerebral sickling, priapism, or multiorgan failure. The goal is to reduce HbS to <30%. Consult with haematology for urgent transfusion.
• Long-Term Management: Hydroxyurea can increase HbF, reducing the frequency of sickling crises. Bone marrow transplantation is a potential curative option for eligible patients.

References

• Sickle Cell Anaemia: A Review