Paeds · haematology-oncology-and-transfusion
Sickle cell disease: diagnosis and health maintenance
Also known as Sickle cell disease · SCD · Sickle cell anaemia · HbSS disease · Hemoglobin SC disease · Sickle cell disorder
Fellowship guide to the diagnosis and health maintenance of sickle cell disease in children. Covers the autosomal recessive haemoglobinopathy born of the glutamate-to-valine substitution at beta-globin position six, the newborn-screen diagnosis by haemoglobin electrophoresis or high-performance liquid chromatography, and the four pillars of lifelong care: penicillin V prophylaxis from two months at 125 mg twice daily under three years and 250 mg twice daily at three years and over to five years, encapsulated-organ immunisation, hydroxyurea from nine months at a starting dose of 20 mg per kg per day, and annual transcranial Doppler surveillance from ages two to sixteen with chronic transfusion keeping HbS under 30 percent when the velocity reaches 200 cm per second or more.
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Target exams
Red flags
- A febrile child with sickle cell disease has overwhelming encapsulated sepsis until proven otherwise, because functional asplenia develops in the first years of life
- An abnormal transcranial Doppler with a time-averaged mean velocity of 200 cm per second or more is a pre-stroke state that demands urgent commencement of chronic transfusion
- A sudden fall in haemoglobin with a rapidly enlarging spleen is acute splenic sequestration, a hypovolaemic emergency in an infant
- Stopping chronic transfusion after a transcranial Doppler normalises risks reversion to abnormal flow and silent or overt stroke, per STOP II
- A child on hydroxyurea with a falling neutrophil count has dose-related myelosuppression that needs a dose hold or reduction
- Acute pallor, breathlessness and a drop in haemoglobin of 20 g per litre or more in the chest suggests acute splenic sequestration, an aplastic crisis from parvovirus B19, or acute chest syndrome
Life stages
Care settings
Clinical exam formats
Board mappings
- Recognises the newborn-screen diagnosis of sickle cell disease by haemoglobin electrophoresis or high-performance liquid chromatography and names the HbSS, HbSC and HbS beta-thalassaemia genotypes
- States that oral penicillin prophylaxis starts by two months of age and continues to five years, at 125 mg twice daily under three years and 250 mg twice daily at three years and over
- Names hydroxyurea as the disease-modifying backbone and transcranial Doppler as the annual stroke screen from ages two to sixteen
- Explains the glutamate-to-valine substitution at beta-globin position six, the polymerisation of deoxygenated haemoglobin S, and the cascade of sickling, vaso-occlusion and chronic haemolysis
- Coordinates the health-maintenance package of penicillin prophylaxis, encapsulated-organ immunisation, hydroxyurea from nine months, and transcranial Doppler surveillance with chronic transfusion for abnormal velocities
- Appraises the PROPS penicillin trial, the Multicenter Study of Hydroxyurea, the STOP and STOP II transfusion trials, and the TWiTCH non-inferiority trial
- Penicillin V prophylaxis is 125 mg twice daily under three years and 250 mg twice daily at three years and over, started by two months and continued to five years
- Hydroxyurea starts at 20 mg per kg per day and is escalated to the maximum tolerated dose, with a blood count every four weeks
- An abnormal transcranial Doppler is a time-averaged mean velocity of 200 cm per second or more, and chronic transfusion keeps HbS under 30 percent
- Counsels the family of a newly diagnosed infant on the inheritance, the penicillin and immunisation plan, the hydroxyurea decision, and the lifelong surveillance
- Builds the multidisciplinary health-maintenance plan that runs haematology, primary care, immunisation, transcranial Doppler surveillance, and transition together
- Synthesises the school-age child on hydroxyurea with an abnormal transcranial Doppler into a transfusion strategy with iron-overload monitoring
- Level 1: Recognition of the newborn-screen result and the initiation of penicillin prophylaxis and encapsulated-organ immunisation
- Level 2: Application of hydroxyurea from nine months and annual transcranial Doppler surveillance with referral for abnormal velocities
- Level 3: Coordination of chronic transfusion for stroke prevention, iron-overload management, and transition to adult haemoglobinopathy care
- The genetics of the HBB p.Glu6Val mutation, the genotype spectrum, and the inheritance of sickle cell trait
- The newborn-screen and confirmatory haemoglobin methods, the penicillin doses, and the hydroxyurea starting dose
- The transcranial Doppler thresholds, the STOP and STOP II evidence, and the encapsulated-organ immunisation schedule
- Communication of the newborn diagnosis, the inheritance, and the health-maintenance plan to the family
- Structured assessment of the child with sickle cell disease for growth, spleen size, pallor, and developmental surveillance
- Recognition and counselling around the stroke-prevention pathway of transcranial Doppler and chronic transfusion
- Sickle cell disease as an autosomal recessive haemoglobinopathy diagnosed by newborn screening with haemoglobin electrophoresis or high-performance liquid chromatography
- Penicillin prophylaxis, encapsulated-organ immunisation, hydroxyurea, and transcranial Doppler surveillance as the pillars of health maintenance
- The STOP trial evidence that chronic transfusion prevents first stroke in children with abnormal transcranial Doppler velocities
- Recognition of the newborn-screen diagnosis and the urgency of starting penicillin prophylaxis by two months of age
- Application of hydroxyurea from nine months and annual transcranial Doppler screening from ages two to sixteen
- Coordination of the multidisciplinary haemoglobinopathy team and the transition to adult care
- Canadian approach to universal newborn screening and confirmatory testing for sickle cell disease
- Penicillin prophylaxis, pneumococcal and meningococcal immunisation, hydroxyurea, and transcranial Doppler surveillance
- Chronic transfusion for stroke prevention and iron-chelation management
Overview & Definition
A single changed letter in the DNA, a single amino acid swapped in the haemoglobin molecule, can reshape a whole childhood. Sickle cell disease is the inherited haemoglobinopathy in which a glutamate is replaced by a valine at the sixth position of the beta-globin chain, producing an abnormal haemoglobin called haemoglobin S. When haemoglobin S gives up its oxygen, it sticks to itself, forms long rigid fibres, and bends the red cell into the crescent or sickle shape that gives the disease its name. The sickled cell blocks small blood vessels and tears itself apart, so the child lives with pain, chronic anaemia, and organ injury. [11]
The disease is common, and it is global. It is most frequent in children whose families come from sub-Saharan Africa, but it also appears across the Mediterranean, the Middle East, and South Asia, because the sickle gene once protected against falciparum malaria. Most children today are diagnosed within the first weeks of life through newborn screening, before they have been ill at all, and the work of the paediatric team is to keep them well through a package of prophylaxis, immunisation, and surveillance. [5]
Three ideas make this topic central to the paediatric exam. The first is diagnosis, because the haemoglobin electrophoresis or high-performance liquid chromatography read from a heel-prick blood spot settles the genotype in the newborn period. The second is penicillin prophylaxis, because a tablet given twice a day transformed the survival of these children. The third is the surveillance of stroke, because the transcranial Doppler finds the child at risk before the stroke happens, and chronic transfusion stops it. The 2014 National Heart, Lung, and Blood Institute panel report and the 2020 American Society of Hematology cerebrovascular guideline together define modern care and remain the most testable sources. [5][8]
References11ShowHide
- [1]Gaston MH, Verter JI, Woods G Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med, 1986.PMID 3086721
- [2]Charache S, Terrin ML, Moore RD Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med, 1995.PMID 7715639
- [3]Adams RJ, McKie VC, Hsu L Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med, 1998.PMID 9647873
- [4]Abboud MR, Yim E, Musallam KM Discontinuing prophylactic transfusions increases the risk of silent brain infarction in children with sickle cell disease: data from STOP II. Blood, 2011.PMID 21633086
- [5]Yawn BP, Buchanan GR, Afenyi-Annan AN Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA, 2014.PMID 25203083
- [6]Hankins JS, Aygun B, Nottage K From infancy to adolescence: fifteen years of continuous treatment with hydroxyurea in sickle cell anemia. Medicine (Baltimore), 2014.PMID 25526439
- [7]Ware RE, Davis BR, Schultz WH Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet, 2016.PMID 26670617
- [8]DeBaun MR, Jordan LC, King AA American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv, 2020.PMID 32298430
- [9]Lebensburger JD, Miller ST, Howard TH Influence of severity of anemia on clinical findings in infants with sickle cell anemia: analyses from the BABY HUG study. Pediatr Blood Cancer, 2012.PMID 22190441
- [10]Quinn CT, Rogers ZR, McCavit TL Improved survival of children and adolescents with sickle cell disease. Blood, 2010.PMID 20194891
- [11]Rees DC, Williams TN, Gladwin MT Sickle-cell disease. Lancet, 2010.PMID 21131035