In 1993, we had one paediatric patient with Sickle Cell Disease (SCD) at PMH. We now have 55 patients under age 17. That may not sound like many, but this is a chronic disease with many challenges facing the patients, their families and the staff caring for them through their lifetime.
The pathophysiology is of an acute and chronic vasculopathy and hence comparable to diabetes. If we manage these patients well as infants, children and adolescents, they will become healthy adults. Specialised multidisciplinary hospital service provision, research and education is lagging behind the change in demographics over the past 30 years with migrants and refugees from countries where the incidence of SCD is higher.
Sickle Cell Anaemia (Hb SS) is a multisystem disease associated with episodes of acute illness and progressive organ damage. There is a single mutation in the beta globin gene resulting in replacement of glutamic acid by valine in position 6 of the beta chain. If present in one gene, the patient has a sickle cell trait (Hb S) and is largely symptom-free. If in both genes, the patient has Hb SS. Sickle disease is any condition in which the inheritance of Hb S can lead to the sickle shape of red blood cells and therefore includes co-inheritance of Hb S with another beta globin chain defect, such as Hb C or a beta thalassaemia.
This disease largely affects people with African and Middle Eastern ethnicity as the malaria parasite does not enjoy Hb SS. These patients are not immune to malaria and still require prophylaxis when heading to a malarial risk area.
The global burden of SCD is over six million cases including 300,000 births annually. Australia does not have a coordinated approach to antenatal/newborn screening. Early diagnosis and introduction of therapy can prevent complications. A full blood picture may have normal indices. The film features should detect some sickle cells, target cells and may show signs of hyposplenism depending on age.
The diagnosis in a high-risk individual can be made at any age by performing a full blood picture and haemoglobin study to detect the sickle haemoglobin in a carrier (there will be normal Hb A) and an individual with SCD (who will show a peak where the Hb S is detected). Regardless of age, an urgent sickle solubility test can be performed to detect the presence of Hb S on a sample. This cannot differentiate a sickle trait from SCD.
SCD has been recognised as an acute and chronic inflammatory disease. Multiple cell types and molecules are involved in its inflammatory pathways. The complications of this pathophysiology are multiple and affect all organs (Fig. 1) and any age group. When a vaso-occlusive crisis occurs, the patient presents in severe pain. They require urgent therapy (including hydration, pain relief). In some cultures, this disease is still stigmatised and there may be family denial.
There are international guidelines for standards and recommendations for acute emergency presentations and ongoing therapy and surveillance. Australian guidelines are in development.
One of the main changes to infant and childhood mortality from SCD has been the international early introduction of prophylactic penicillin and immunisation against encapsulated organisms.
Up to 98% of children with SCD will now survive to age 18. However, these children would have ongoing complications from the vasculopathy were it not for the introduction of oral hydoxyurea, an effective (few side effects) and relatively inexpensive therapy optimally introduced at about nine months of age, when the fetal haemoglobin falls and the Hb S rises to a more critical level.
Its main mechanism is to increase production of Hb F (adults usually have <1% Hb F) thus reducing the total amount of Hb S. Hydroxyurea causes a mild neutropenia reducing some inflammatory aspects of the disease. Studies have shown, hydroxyurea reduces vaso-occlusive crises, hospital admissions, anaemia, haemolysis, strokes and improves survival.
Regular surveillance for vasculopathy is also a part of the international guideline. This involves transcranial doppler (for evidence of cerebral stenosis), head and hip MRI, renal, ophthalmology, cardiac, dental, respiratory, neurodevelopmental, and endocrine surveillance.
Families may have come to Australia as refugees with additional trauma due to war and conflict, with English not their first language. Interpreter services, clinical psychology, occupational therapy and social work services are essential to an integrated, focused multidisciplinary approach.
Despite adequate hydroxyurea doses, some patients (10-15%) still experience complications – cerebral vasculopathy, acute chest syndrome and recurrent vaso-occlusive disease. These patients require regular red cell transfusion to reduce the Hb SS. Automated red cell exchange using apheresis is currently used as an emergency procedure at PCH (acute chest syndrome, acute neurological presentation and severe vaso-occlusive crisis not responding to usual therapy).
However, it is now considered the standard of care internationally for patients having regular red cell transfusions for SCD. This allows longer intervals between transfusions, lowers Hb S most efficiently, lowers pro-inflammatory markers and has a possible reduction of allo-immunisation. It also lowers iron stores and patients do not have to take oral iron chelation therapy.
Apheresis is faster, but it also requires skilled nursing, is more expensive than standard transfusion, sometimes requires central venous access and may have an increased donor red cell exposure. The apheresis team are currently working on an apheresis service for PCH that can deliver this procedure, but it requires funding and trained staff.
Child and adult survival with SCD is improving but there is much work to be done. Transition to adult care (recognised as a time of risk) in WA is a problem as there is no funding for any adult specialised SCD haematology service. The Australian Sickle Cell Advocacy group is available as a support for patients and families.
Australian guidelines and new treatments are on the horizon giving grounds for optimism.
Key messages
- Demographic changes have seen a steep rise in SCD prevalence in Australia
- Better treatments are improving survival
- Australian guidelines are being developed as are new treatments.
– References available on request
Author competing interests – nil