Makindo Medical Notes.com

Inform haematology if a known HbSS/SC or equivalent patient is admitted. RBCs take up a sickle-like shape in settings of deoxygenation.

About

• Chronic haemolytic anaemia occurring almost exclusively in those of Afro-Caribbean origin.
• Homozygous sickle cell anaemia (HbSS) commonest and most severe form in the UK, accounting for 70% of patients.
• Compound heterozygotes for HbS and HbC (SC disease) account for the majority of the remainder. Other compound heterozygotes can lead to sickling disorders.
• Most patients with these disorders carry a haemoglobinopathy card.
• The heterozygous carrier or trait state gives some protection to malaria HbAS

Aetiology

• Point mutation changes valine instead of glutamic acid at 6th amino acid of beta-globin chain
• The HB SS is less soluble as valine is relatively hydrophobic
• Hb SS contains 2 normal alpha and 2 defective Beta globin chains
• Haemoglobin electrophoresis is used in the diagnosis of sickle cell disease and trait
• This fits into a corresponding position of the alpha chain - this leads to polymerisation and sickling
• At low Oxygen tensions the HbS polymerizes inside the RBC leading to sickling

Sickling precipitant

• Deoxygenation/high altitude, Dehydration, Pregnancy
• Infection / Fever / Rapid temperature changes
• Can easily end up in a downward spiral of sickling complications precipitating more sickling

Types of Haemoglobinopathy

• Sickle cell anaemia HbSS - Only have HbS and no HbA as they have no normal Beta globin chains. Usually anaemic.
• SC disease HbSC: HbS from one parent and HbC from the other. No HbA. A milder form of sickle cell disease but can have crises. Hb can be normal
• Sickle ? thalassaemia HbS + Normal Beta chain from other parent
• HbS from one parent and Beta thalassaemia from the other. Symptoms like Sickle cell anaemia
• Sickle cell trait: HbS - Only have HbS from one parent. Only 40% of Hb is HbS. Clinically silent but can pass on the disease

Clinical

• Initial medical assessment should be performed to delineate the type of sickle cell crisis and to detect any of the following medical complications which require specific therapy
• Look for and manage Infection (fever), Dehydration
• Acute chest syndrome (fever, dyspnoea, chest or rib or vertebral pain, falling Hb, hypoxia, chest signs, RR > 25/min, hypoxia less than 80% on room air)
• Severe anaemia (? Aplastic crisis)
• Cholecystitis (? obstructive jaundice)
• Splenic enlargement (? Sequestration)
• Neurological signs (? Cerebral sickling) can cause large and small vessel infarcts and haemorrhagic strokes from aneurysmal dilation of small vessels in response to hypoxia
• Priapism: painful unwanted erection

Complications

• Haemolytic anaemia, Acute chest syndrome
• Salmonella osteomyelitis, Pneumococcal infection
• Sickling crisis, Avascular necrosis of the hips
• Renal concentrating defects, Aplastic crises, Renal failure
• Pulmonary fibrosis, Stroke, Hepatosplenomegaly
• Osteoporosis - vertebral collapse
• Priapism - sequestration of red cells in corpus cavernosum
• Renal papillary necrosis - loin pain, urinary obstruction, haematuria
• Bone pain due to sickling and avascular necrosis of femoral head
• Bone pain dactylitis or swollen joints
• Skin ulcers, Pigment gallstones
• Splenic infarction - autosplenectomy
• Bleeding in the anterior chamber of eye - hyphema
• Infection - pneumococcal, HiB vaccination

Investigations

• FBC : anaemia, WCC elevated ? infection. Reticulocyte count
• Blood and urine cultures - sepsis screen as needed
• Oxygen sats and ABG: hypoxia - chest syndrome / PE
• ECG: signs of ischaemia
• U&E, LFTS, LDH, Bilirubin, Haptoglobin: Haemolysis, Dehydration
• Group and save
• CXR: consolidation
• CTPA: if PE suspected
• Troponin, Dimer, Lactate if needed
• HB electrophoresis
• X-ray any painful bones/fever ?osteomyelitis
• CT/MR Brain : acute CNS neurology

Management of Acute sickling crisis

• Fluid balance chart is essential and replacement IV N Saline. If difficult to ensure the patient is able to drink > 60 ml/kg/24 hours then oral hydration is sufficient. If an inadequate oral intake occurs in a patient with poor peripheral venous access then NG fluid is preferred. The central line where transfusion is required
• Opiate analgesia is usually required for painful crises and should be administered within 30 mins of presentation to the hospital aiming to achieve effective analgesia by 60 minutes. Start a pain chart. Morphine is the opiate of choice. A loading dose of Morphine 2.5-5mg IV in 10ml normal saline so further titration to effect can be given over the next 10 minutes. The initial dose required for effective analgesia can be repeated after one hour but an infusion as detailed below or PCA may be considered. Monitor for hypoxia every 30 minutes until pain settled and then every 2 hours. If respiratory rate <10/ second stop opiates, if < 6 give Naloxone. Add laxatives.
• NSAIDS can be useful adjunctive therapy and regular Diclofenac 50 mg 8 hourly or Ibuprofen 400 mg TDS as well as Paracetamol 1 g QDS should be prescribed if there are no contraindications
• Antibiotics: If the patient is febrile or has a history suggestive of an infective cause of the sickle crisis they should be commenced on antibiotics. Augmentin is the antibiotic of choice in most cases unless Penicillin allergic
• Anxiolytic: Haloperidol 1–3 mg oral or IM as required.
• Target Oxygenation: aim for O₂ saturation 95%. Patients who are having a sickling crisis should be given 35% Oxygen or higher to breathe if their O₂ saturation is less than 95%
• Exchange Transfusion: The aim of an exchange transfusion is to replace sickle blood with HbAA. Exchange transfusion should be discussed with a Consultant. The indications for urgent exchange transfusion are Sickle chest crisis, Cerebral sickling, Priapism, Multiorgan failure. Red cell exchange is preferably done using the cell separator. However, emergency exchanges may have to be performed manually if necessary out of hours by repeated venesection and transfusion. Blood should be Rhesus and Kell genotyped for the patient and Blood Bank should be contacted as soon as an exchange transfusion is planned. Hb A and S levels should be sent to the haematology laboratory after exchange transfusion. A Hb S level of < 30% is the goal of this therapy
• Long term Hydroxyurea/Hydroxycarbamide is useful in increasing HbF which decreases the frequency of crises.
• Long term consider Bone marrow transplantation
• Screen at risk patients before surgery/pregnancy

References

• Sickle Cell Anaemia: A Review