Sickle Cell Anaemia

Definition

Sickle cell anaemia is the most severe form of sickle cell disease, an inherited disorder of haemoglobin. An abnormal haemoglobin (haemoglobin S, HbS) causes red blood cells to distort into a rigid, curved sickle shape when oxygen levels fall. Those deformed cells break down early and obstruct small blood vessels, producing a lifelong disease of anaemia, episodic severe pain and progressive organ damage. It is most common in people of African, Mediterranean, Middle Eastern and Indian ancestry.¹

Pathophysiology

A single amino-acid substitution in the β-globin chain produces HbS, which polymerises when deoxygenated. The polymer distorts the red cell membrane into the characteristic sickle shape. Two consequences follow, and almost every feature of the disease traces back to one of them.

First, sickled cells are fragile. They survive around 10–20 days rather than 120, giving chronic haemolytic anaemia with jaundice, gallstones and a high cardiac output state. Free haemoglobin released into the plasma consumes nitric oxide, which drives vascular tone upwards and contributes to pulmonary hypertension.

Second, sickled cells are stiff and sticky. They adhere to activated endothelium and to each other, obstructing capillaries and small vessels — vaso-occlusion — which starves tissue of oxygen, causes ischaemic pain and, repeated over years, infarcts organs. Hypoxia, dehydration, acidosis, infection, cold and physical or emotional stress all promote sickling, which is why the triggers listed later in this page are clinically important rather than incidental advice.

In the lung the two mechanisms converge. Rib and chest pain from vaso-occlusion causes splinting and shallow breathing, which produces atelectasis and hypoxaemia, which promotes further sickling in the pulmonary vasculature — the cycle that generates acute chest syndrome. This is the single most important pathophysiological point for physiotherapy.

Co-morbidities

Over time the disease damages the spleen (raising the risk of infection with encapsulated organisms), kidneys, brain, eyes, lungs, bones and joints. Gallstones, leg ulcers, avascular necrosis of the hip and shoulder, and pulmonary hypertension are all common. Pregnancy and surgery carry added risk and need planned multidisciplinary care. Asthma is a specific and clinically relevant association: in children with sickle cell anaemia it is associated with a higher rate of both acute chest syndrome and painful crises, so coexisting asthma should be actively identified and properly treated.²

Prevalence

Sickle cell disease is one of the commonest inherited disorders worldwide, concentrated in populations originating from malaria-endemic regions, where carrying one copy of the gene confers a survival advantage. In Australia it is seen mainly in migrant and refugee communities, and numbers are rising with migration patterns. Because it remains uncommon here, delayed recognition and unfamiliarity among clinicians are genuine risks — access to specialist haematology and to clinicians who know the condition matters as much as the treatment itself.

Causes and risk factors

Sickle cell anaemia is caused by inheriting two copies of the sickle β-globin gene, one from each parent — an autosomal recessive pattern. Inheriting one copy gives sickle cell trait, which is usually asymptomatic and is not a mild form of the disease, though it can matter under extreme hypoxic stress. Other genotypes, including HbSC disease and HbS/β-thalassaemia, produce a generally milder but still significant illness.

The disease itself is not caused by anything the person does. What is modifiable is the trigger for a crisis: hypoxia (including altitude and unpressurised flight), dehydration, infection, cold exposure, sudden temperature change, strenuous unaccustomed exertion, alcohol, and physical or emotional stress.

Symptoms

Chronic anaemia

Persistent fatigue, pallor, breathlessness on exertion, reduced exercise tolerance and episodes of jaundice. Because the anaemia is lifelong, many people underestimate how limited they are until it is measured.

Vaso-occlusive painful crises

The defining feature: sudden severe pain, most often in the bones of the back, chest, arms and legs, lasting days. Pain is frequently under-treated, and patients attending emergency departments repeatedly for opioid analgesia are too often assumed to be drug-seeking rather than in a medical emergency — a well-documented and serious failure of care.

Acute chest syndrome

Acute chest syndrome (ACS) is a leading cause of hospitalisation and death. It presents with chest pain, fever, cough, breathlessness and new shadowing on the chest X-ray, and can deteriorate rapidly over hours. Triggers include infection, a painful crisis, fat embolism from infarcted marrow, and under-breathing because of chest and rib pain.³

Infection and splenic dysfunction

Repeated splenic infarction leaves most patients functionally asplenic in childhood, with lifelong susceptibility to pneumococcal and other encapsulated organisms. Fever in sickle cell disease is treated as a potential emergency.

Warning signs

Diagnosis

Why diagnosis matters

Diagnosis — often at newborn screening — allows early preventive care: vaccination, penicillin prophylaxis, hydroxyurea, transcranial Doppler surveillance and specialist follow-up. This package greatly reduces complications and childhood death, and the difference between diagnosed and undiagnosed disease in the first five years of life is stark.

How is it diagnosed?

Diagnosis rests on a full blood count and blood film showing anaemia, sickle cells, target cells and Howell–Jolly bodies, together with haemoglobin electrophoresis or high-performance liquid chromatography (HPLC) to identify and quantify HbS, HbF and HbA. Genetic testing confirms the genotype and is used for family studies.

Newborn and antenatal screening

Newborn screening detects the disease before the first crisis in many countries, allowing prophylaxis to start in infancy. Antenatal screening and carrier testing allow informed reproductive choice, and genetic counselling is offered to couples where both carry the trait.

Pathology and biomarkers

Baseline haemoglobin, reticulocyte count, lactate dehydrogenase and bilirubin quantify the degree of haemolysis. A rising reticulocyte count with falling haemoglobin suggests haemolytic crisis; a falling reticulocyte count suggests aplastic crisis, often parvovirus B19. HbF percentage is monitored as a marker of hydroxyurea response.

Radiology and lung assessment

Chest X-ray is essential in any acute chest presentation and defines ACS. Magnetic resonance imaging identifies avascular necrosis and silent cerebral infarcts. In the chronically breathless patient, spirometry with gas transfer and pulse oximetry help characterise the restrictive defect and chronic hypoxaemia of sickle cell lung disease, and echocardiography screens for pulmonary hypertension.

Investigations for related conditions

Ongoing surveillance is a defined programme rather than ad hoc testing: transcranial Doppler in children to identify those at high stroke risk, in whom a regular transfusion programme markedly reduces first stroke;⁴ annual retinal screening; kidney function and urinary protein; echocardiography for pulmonary hypertension; and prompt investigation of any acute chest symptom.

Management

Management and goals

The aims are to reduce the frequency and severity of crises, prevent and promptly treat acute complications — above all ACS and stroke — limit cumulative organ damage, and support a full life in education, work and family. Care is coordinated by a haematology team, with shared care close to home.

Preventive care

• Vaccination — pneumococcal, meningococcal, Haemophilus influenzae type b, annual influenza and COVID-19.
• Penicillin prophylaxis from infancy, given functional asplenia.
• Folic acid supplementation to support high red cell turnover.
• Trigger avoidance — hydration, warmth, prompt treatment of infection, avoiding sudden cold and unaccustomed maximal exertion.
• Hydroxyurea for those with recurrent crises or ACS.

Treating a painful crisis

Prompt, adequate analgesia — frequently opioid, given without delay and titrated to effect — together with hydration, oxygen if hypoxaemic, warmth and treatment of any infection. Individualised pain protocols held on file reduce delay and dispute at presentation. Adequate analgesia is not merely humane: it is what allows the deep breathing that prevents ACS.

Managing acute chest syndrome

ACS is treated with oxygen, effective analgesia, antibiotics covering atypical organisms, careful fluid balance, incentive spirometry and, in severe or deteriorating cases, simple or exchange transfusion, with escalation to non-invasive or invasive ventilation where required. Guidelines set out the pathway and emphasise early recognition.⁵

Preventing acute chest syndrome

This is where physiotherapy has a directly evidenced role. Incentive spirometry used regularly during a painful crisis involving the chest, ribs or back significantly reduces the incidence of pulmonary complications compared with usual care — a simple, cheap intervention with a substantial effect, and one that depends on pain being controlled well enough to allow deep inspiration.⁶

Transfusion

Simple transfusion corrects severe anaemia; exchange transfusion reduces the proportion of sickle haemoglobin rapidly and is used in ACS, stroke and before major surgery. Regular transfusion programmes prevent first and recurrent stroke in high-risk children. Iron overload and alloimmunisation are the principal long-term costs, requiring chelation and careful matching.

Curative and disease-modifying options

Allogeneic haematopoietic stem-cell transplant from a matched sibling is curative in selected patients. Gene therapy and gene editing have moved from experimental to available in some settings for severe disease.

Identifying deterioration

Escalating pain unresponsive to the usual regimen, any new respiratory symptom, fever, neurological change, priapism, sudden pallor with lethargy (aplastic or splenic sequestration crisis) or falling oxygen saturation all require urgent assessment. In hospital, a rising respiratory rate and falling saturations in someone with chest or rib pain should be assumed to be evolving ACS until proven otherwise.

Action plan

Every patient should hold a written plan naming their haematology unit and after-hours contact, their individual analgesia regimen, their baseline haemoglobin and oxygen saturation, transfusion history and antibody status, and the symptoms that mean present immediately. Carrying it to any emergency department shortens the delay that costs most in this condition.

Medications

Medications for sickle cell anaemia

Hydroxyurea is the mainstay disease-modifying therapy: it raises fetal haemoglobin, which interferes with HbS polymerisation, and reduces the frequency of painful crises, episodes of acute chest syndrome, transfusion requirement and hospital admission.⁷ Prophylactic antibiotics (penicillin) and folic acid are standard. Analgesia for crises ranges from paracetamol and non-steroidal anti-inflammatories through to strong opioids.

Correct use of medications

Hydroxyurea requires regular blood monitoring for myelosuppression and takes weeks to months to show benefit — expectations set early prevent premature abandonment. Penicillin prophylaxis is lifelong in most patients and is easily and quietly dropped in adolescence, which is exactly when the consequences appear. Adequate hydration is part of the medication plan, not separate from it.

Analgesia and breathing

The link between pain relief and respiratory outcome deserves stating explicitly to patients and to ward staff. Under-treated chest or rib pain causes splinting, atelectasis and ACS; over-sedation depresses ventilation and does the same. The target is pain controlled enough to permit deep breathing and incentive spirometry, with respiratory rate and saturations monitored — a genuinely collaborative task between medical, nursing and physiotherapy staff.

Newer disease-modifying agents

Beyond hydroxyurea, additional agents targeting adhesion and haemoglobin polymerisation are used in specialist care, and gene-editing approaches have produced sustained increases in fetal haemoglobin with elimination of vaso-occlusive crises in early trials.⁸ Availability in Australia is limited and evolving — verify current TGA and PBS status.

Multi-system manifestations

Lungs and airways

Acute chest syndrome, chronic sickle cell lung disease with a restrictive defect and reduced gas transfer, pulmonary hypertension, and a high prevalence of asthma and airway hyper-responsiveness. Sleep-disordered breathing and nocturnal hypoxaemia are common and provoke sickling overnight.

Brain and stroke

Overt ischaemic stroke, most frequent in childhood, and silent cerebral infarcts that cause no acute deficit but accumulate to produce cognitive and educational difficulty. Transcranial Doppler surveillance and transfusion have transformed this risk.

Spleen and infection

Functional asplenia from repeated infarction, and in young children acute splenic sequestration — rapid pooling of blood in the spleen causing profound anaemia and shock, a paediatric emergency that parents are taught to detect by palpation.

Kidneys

Impaired urinary concentration from early childhood (contributing to dehydration and therefore to crises), haematuria, proteinuria and progressive sickle cell nephropathy, with a minority reaching end-stage kidney disease.

Bones and joints

Bone infarction is the commonest site of crisis pain. Avascular necrosis of the femoral and humeral heads causes chronic pain, stiffness and progressive loss of function, often in young adults, and frequently leads to joint replacement. Vertebral end-plate infarction produces characteristic H-shaped vertebrae and back pain. Osteomyelitis must be distinguished from infarction.

Eyes, heart and skin

Proliferative sickle retinopathy threatens vision and is screened for annually. Chronic anaemia produces a high-output cardiac state with left ventricular hypertrophy, and pulmonary hypertension carries a poor prognosis. Chronic leg ulcers over the malleoli are painful, slow to heal and functionally limiting.

Living with sickle cell anaemia

Avoiding triggers

Staying warm and well hydrated, dressing for sudden temperature change, avoiding cold water immersion and unaccustomed maximal exertion, and treating infection promptly. These are not lifestyle suggestions but the main levers the patient personally controls.

Nutrition and hydration

Energy and folate requirements are raised by continuous red cell turnover, and growth may be delayed in childhood. Generous fluid intake is protective, and dietetic input helps where growth or weight is a concern.

Sleep

Nocturnal hypoxaemia and sleep-disordered breathing are common and provoke overnight sickling. Snoring, witnessed apnoea or morning headache warrants a sleep assessment; enlarged tonsils in children are a frequent and treatable cause.

Exercise and activity

Being sedentary is not protective. Moderate-intensity endurance training in people without severe complications is feasible and improves muscle function and exercise capacity without provoking crises, provided intensity is submaximal, progression is gradual, and hydration and warmth are managed.⁹ Practical guidance — warm up, avoid maximal and anaerobic effort, drink before and during, stop and rest early, avoid cold pools and post-exercise chilling — is more useful than a blanket restriction.

Travel and altitude

Hypoxia at altitude and in unpressurised aircraft can trigger crises. Commercial flights are generally safe, though hydration matters; travel plans, immunisations and a letter summarising the condition are best organised in advance with the haematology team.

School, work and mental health

Frequent absence, cognitive effects of silent infarcts, chronic pain and fatigue all affect education and employment, and adjustments are reasonable and often straightforward. Chronic pain, uncertainty and repeated poor experiences of emergency care carry a real mental-health burden, and anxiety and depression should be asked about directly rather than waited for.

Prognosis

With comprehensive care, survival and quality of life have improved substantially: newborn screening, penicillin prophylaxis, vaccination, transcranial Doppler surveillance, transfusion programmes and hydroxyurea have together shifted this from a disease of childhood death to one of adult chronic illness. It remains serious. Acute chest syndrome, stroke and pulmonary hypertension are the major causes of death, and cumulative organ damage — kidney, lung, bone and brain — determines long-term function. Curative transplant and emerging gene therapies are changing the outlook again for those able to access them.

Role of the physiotherapist

Respiratory physiotherapy has a direct, evidenced role in preventing and treating acute chest syndrome. During any crisis involving the chest, ribs, back or upper abdomen, regular incentive spirometry and deep-breathing exercises reduce atelectasis and pulmonary complications, and are among the few interventions in this condition with randomised evidence behind them.⁶ Delivering them well means working with the pain team, because the technique only works if the patient can take a deep breath — escalating analgesia is often the physiotherapy intervention. Positioning, gentle airway clearance where secretions are retained, and early mobilisation complete the acute picture, with saturations and respiratory rate monitored throughout.

Between crises the role is rehabilitative. Skeletal muscle function is measurably impaired in sickle cell disease, contributing to fatigue and reduced exercise capacity independently of the anaemia,¹⁰ and carefully prescribed submaximal exercise and reconditioning improves it safely. Physiotherapy also addresses the musculoskeletal burden — avascular necrosis of the hip and shoulder, joint protection, gait, pre- and post-operative rehabilitation for joint replacement, and chronic back pain from vertebral infarction — and uses breathing retraining and pacing for breathlessness, fatigue and the anxiety that accompanies both. Across all of it, the physiotherapist is often the clinician with most contact time, and therefore best placed to notice the early breathlessness that signals ACS.

Part 1 · References

1. Ware RE, de Montalembert M, Tshilolo L, Abboud MR. Sickle cell disease. Lancet 2017;390(10091):311–323.
2. Boyd JH, Macklin EA, Strunk RC, DeBaun MR. Asthma is associated with acute chest syndrome and pain in children with sickle cell anemia. Blood 2006;108(9):2923–2927.
3. Vichinsky EP, Neumayr LD, Earles AN, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. N Engl J Med 2000;342(25):1855–1865.
4. Adams RJ, McKie VC, Hsu L, et al. 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;339(1):5–11.
5. Howard J, Hart N, Roberts-Harewood M, Cummins M, Awogbade M, Davis B. Guideline on the management of acute chest syndrome in sickle cell disease. Br J Haematol 2015;169(4):492–505.
6. Bellet PS, Kalinyak KA, Shukla R, Gelfand MJ, Rucknagel DL. Incentive spirometry to prevent acute pulmonary complications in sickle cell diseases. N Engl J Med 1995;333(11):699–703.
7. Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med 1995;332(20):1317–1322.
8. Frangoul H, Altshuler D, Cappellini MD, et al. CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. N Engl J Med 2021;384(3):252–260.
9. Gellen B, Messonnier LA, Galactéros F, et al. Moderate-intensity endurance-exercise training in patients with sickle-cell disease without severe chronic complications (EXDRE): an open-label randomised controlled trial. Lancet Haematol 2018;5(11):e554–e562.
10. Merlet AN, Chatel B, Hourdé C, et al. How sickle cell disease impairs skeletal muscle function: implications in daily life. Med Sci Sports Exerc 2019;51(1):4–11.

References are numbered in citation order (Vancouver/BMJ style) and were current at the time of writing. Guidelines are living documents — verify against the latest version before clinical use.