What causes the pain in sickle cell crisis?

Vaso-occlusive crisis (VOC) occurs when deoxygenated haemoglobin S polymerises, deforming red blood cells into a rigid crescent shape. These abnormal cells obstruct small vessels, causing ischaemia in bone marrow, muscles, and organs. Pain is typically severe, acute, and affects the long bones, back, chest, and abdomen. It is often described as the worst pain imaginable. Triggers include dehydration, cold exposure, infection, psychological stress, hypoxia, and exertion. Not every crisis has a clear precipitant. Pain assessment should use validated tools (numerical rating scale or FACES for children). Undertreating sickle pain is a major problem — GPs should treat with the same urgency as other severe acute pain.

Who is at risk of sickle cell disease in Australia?

SCD is most prevalent in people of Sub-Saharan African origin (particularly West African countries — Nigeria, Ghana, Sudan, South Sudan, Somalia), Middle Eastern origin, Indian subcontinent (especially Gujarat), and Mediterranean ancestry (southern Italy, Greece, Turkey). Australia's growing ATSI and refugee populations from Sub-Saharan Africa mean SCD is increasingly encountered in general practice outside specialist centres. The sickle cell trait (HbAS) — one copy — is generally benign but important for genetic counselling. Newborn screening for haemoglobinopathies is conducted in all Australian states and territories and most states include SCD.

Is hydroxyurea safe for long-term use?

Yes. Hydroxyurea (hydroxycarbamide) has over 30 years of clinical evidence supporting safety and efficacy. The landmark MSH trial showed ~50% reduction in painful crises, and the Steinberg 17.5-year follow-up demonstrated no increase in cancer risk and significant survival benefit. It works by increasing foetal haemoglobin (HbF), which inhibits HbS polymerisation. In Australia it is PBS-listed for SCD, typically initiated by a haematologist. Monitoring: FBC every 2–4 weeks during dose titration, then 3-monthly when stable; aim for mild leucopenia (WBC 5–8 × 10⁹/L) as a marker of adequate dosing without toxicity. Contraindicated in pregnancy.

What vaccinations does a person with sickle cell disease need?

People with SCD have functional asplenia — the spleen is progressively destroyed by repeated infarction — making them highly susceptible to encapsulated bacterial infections (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis). The Australian Immunisation Handbook and ATAGI recommend: Prevenar 20 (or Prevenar 13 + PPSV23) pneumococcal; MenACWY + MenB meningococcal; Hib; annual influenza; COVID-19 boosters. Lifelong penicillin V prophylaxis (250–500 mg BD) is recommended from diagnosis through to at least age 5, and often lifelong in practice in adults who have had splenectomy or functional asplenia. Advise patients to carry an asplenia card.

When does a sickle cell pain crisis need emergency care?

Most acute pain crises in adults without complications can be managed at home or in a GP setting with oral opioids and hydration, if there is a clear plan in place. Emergency presentation is required for: severe pain not controlled by home management plan within 1–2 hours; fever ≥38.5 °C with acute illness (risk of sepsis — constitutes a medical emergency); acute chest syndrome (new infiltrate on CXR + respiratory symptoms); neurological symptoms (stroke — emergency exchange transfusion); priapism lasting >2 hours; acute abdomen (splenic sequestration, cholecystitis); severe anaemia below patient's baseline. GPs should have a written crisis management plan for each patient and know which haematology unit the patient is attached to.

Sickle cell disease

Sickle cell disease: the AU general practice approach

By Dr HB Lo, FACRRM Reviewed 26 September 2026 8 min read

Sickle cell disease (SCD) is the most common serious inherited haemoglobin disorder worldwide, affecting Australians of Sub-Saharan African, Middle Eastern, Indian, and Mediterranean ancestry.

SCD causes chronic haemolytic anaemia and episodic vaso-occlusive crises (VOC) — the most common acute GP presentation. Hydroxyurea is the cornerstone disease-modifying therapy; it reduces crisis frequency by ~50% and is PBS-listed.

GP role: manage acute pain crises, co-manage prevention (hydroxyurea, penicillin prophylaxis, vaccination, folic acid), and maintain vigilance for life-threatening complications — acute chest syndrome, stroke, and sepsis from functional asplenia.

What sickle cell disease is

Sickle cell disease (SCD) is an inherited haemoglobin disorder caused by a point mutation in the beta-globin gene, replacing glutamate with valine at position 6 of the beta chain and producing haemoglobin S (HbS). In the deoxygenated state, HbS polymerises, distorting red blood cells into the characteristic crescent (sickle) shape. These rigid, adhesive cells obstruct small blood vessels, causing ischaemia, haemolysis, and the clinical syndromes of SCD.

It is the most common serious inherited haemoglobin disorder globally, predominantly affecting people from Sub-Saharan Africa, the Middle East, the Indian subcontinent, and the Mediterranean — regions historically exposed to falciparum malaria, where the heterozygous trait confers a survival advantage. In Australia, SCD is increasingly encountered in general practice due to migration from affected regions. It is not a rare disease in major AU cities.

The most common genotype is HbSS (homozygous sickle cell anaemia) — the most severe form. Other clinically significant genotypes include HbSC and HbS/β-thalassaemia. The sickle cell trait (HbAS) — one copy — is generally benign, with rare complications (extreme exertion, dehydration, altitude), but is important for genetic counselling.

A. Core clinical — the AU general-practice framework

Presentation patterns the GP must recognise

Vaso-occlusive pain crisis (VOC) is the most common acute presentation. Sudden-onset severe pain in the long bones (femur, tibia, humerus), back, or chest, often without objective signs, lasting hours to days. Triggers: dehydration, cold, infection, stress, hypoxia, exertion, menstruation. eTG and ASH 2020 guidelines emphasise that undertreating sickle pain is a recognised clinical problem — the severity of pain is real regardless of the absence of objective signs.

Chronic haemolytic anaemia — baseline Hb typically 60–90 g/L in HbSS; jaundice, scleral icterus, splenomegaly in children, gallstones (pigment). Do not normalise the low haemoglobin; compare to the patient’s known baseline.

Acute complications requiring emergency recognition:

Acute chest syndrome (ACS) — new chest infiltrate on X-ray + fever/respiratory symptoms + chest pain; mortality risk; requires hospitalisation, transfusion, antibiotics, incentive spirometry
Stroke — ischaemic or haemorrhagic; incidence ~11% before age 20 in untreated HbSS; emergency exchange transfusion
Splenic sequestration — sudden spleen enlargement + acute drop in Hb + circulatory collapse; most common in children under 5
Aplastic crisis — parvovirus B19 infection causing transient red cell aplasia; Hb drops precipitously
Sepsis — functional asplenia; Streptococcus pneumoniae sepsis can be fatal within hours; fever ≥38.5 °C is a medical emergency in SCD

History

Genotype and baseline values — HbS genotype, baseline Hb, baseline reticulocyte count, and baseline creatinine should be known for every SCD patient
Hydroxyurea status — current dose, monitoring bloods, adherence
Crisis frequency and pattern — number of hospital admissions in past year, typical crisis triggers
Vaccination and penicillin prophylaxis status
Specialist attachment — which haematology unit; shared-care plan in place

Examination in acute crisis

Vital signs including oxygen saturation — hypoxia is a red flag and a crisis trigger
Assess for fever (sepsis, ACS), respiratory signs (ACS), focal neurological signs (stroke), abdominal signs (sequestration, cholecystitis, papillary necrosis)
Pain severity using numerical rating scale (0–10) or FACES scale; document

Investigations

FBC — compare Hb to patient’s baseline; reticulocyte count elevation expected; sudden drop suggests aplastic crisis or sequestration
Blood film — sickle cells, target cells, polychromasia; Howell-Jolly bodies indicate functional asplenia
LFTs and bilirubin — elevated unconjugated bilirubin from haemolysis; gallstones common
Creatinine and urine — SCD nephropathy: haematuria, proteinuria, progressive CKD
Ferritin — iron overload in multiply-transfused patients; also marker of inflammation
Oxygen saturation — in every acute presentation

B. Evidence — prevention and disease modification

Hydroxyurea (hydroxycarbamide)

The landmark MSH trial (Charache NEJM 1995) — 299 adults with HbSS and frequent crises — demonstrated a ~50% reduction in painful crises, ACS, and transfusion requirements with hydroxyurea versus placebo. The Steinberg 17.5-year follow-up (Am J Hematol 2010) confirmed survival benefit and no increase in leukaemia or secondary malignancy.

The BABY HUG trial (Wang, Lancet 2011) established that hydroxyurea is safe and effective in children as young as 9 months.

Mechanism: Hydroxyurea increases foetal haemoglobin (HbF) production. HbF does not participate in HbS polymerisation and disrupts the sickle polymer, reducing sickling events.

AU access: PBS-listed under restricted benefit for SCD, initiated by a haematologist. GPs can write continuing prescriptions under specialist direction. Dosing starts at 15 mg/kg/day orally and is titrated up by 2.5–5 mg/kg/day increments every 8–12 weeks to maximum tolerated dose (typically 25–35 mg/kg/day), using mild leucopenia (WBC 5–8 × 10⁹/L) as a dose-finding endpoint per AMH.

Monitoring: FBC every 2–4 weeks during titration; every 3 months when stable. If WBC falls below 3 × 10⁹/L, ANC below 2 × 10⁹/L, or platelet below 80 × 10⁹/L, hold and recheck in 2 weeks.

Contraindications: Pregnancy (teratogenic — contraception essential in reproductive-age patients); breastfeeding.

Infection prevention

Functional asplenia from progressive splenic infarction creates a state of severe susceptibility to encapsulated organisms. The Australian Immunisation Handbook and ATAGI recommend:

Pneumococcal: Prevenar 20 (preferred) or Prevenar 13 → PPSV23 8 weeks later; repeat PPSV23 at 5 years
Meningococcal: MenACWY + MenB (Bexsero); repeat every 5 years
Hib: complete course
Annual influenza + COVID-19 boosters
Hepatitis A and B — complete course; HBV from blood product exposure

Penicillin V prophylaxis: eTG recommends 125–250 mg twice daily in children aged 3 months to 5 years, and continuing at 250–500 mg BD thereafter. The RACGP supports lifelong prophylaxis consideration in adults with severe disease or prior pneumococcal infection. Provide a written emergency action plan for fever.

Folic acid

Daily folic acid 5 mg (children) to 5 mg (adults) supports red cell production in the context of chronic haemolytic anaemia. This is low-cost and universally recommended per eTG.

C. Acute pain crisis management in general practice

ASH 2020 SCD pain guidelines and eTG provide the framework:

Assess severity first. If the patient is systemically unwell (fever ≥38.5 °C, oxygen saturation below 95%, new respiratory symptoms, neurological signs, severe pain uncontrolled), arrange immediate transfer to emergency. In uncomplicated VOC in a patient with a clear crisis pattern, GP management is appropriate.

Analgesic ladder:

Mild–moderate pain: regular paracetamol 1 g QID + ibuprofen 400 mg TDS with food (not in renal impairment); warmth/cold packs
Moderate–severe: add oral opioid — oxycodone IR 5–10 mg 4-hourly or codeine 30–60 mg 4-hourly for adults
Severe, uncontrolled at home: hospitalise for IV/IM opioids

Hydration: Encourage oral fluids (2–3 L/day adults); dehydration is a crisis perpetuator. IV fluids if oral intake inadequate.

Avoid: NSAIDs in renal impairment (SCD nephropathy); pethidine (serotonin syndrome risk, norpethidine seizures — eTG explicitly advises against).

Crisis management plan: Every SCD patient should have a written individualised crisis management plan agreed with their haematologist, specifying when to manage at home, when to attend ED, and which analgesics at which doses. GPs should obtain and review this plan.

D. Australian operations

Haematology shared care

SCD management in Australia is coordinated through state haematology services, typically based at teaching hospitals. Rural and remote patients access these via telehealth and visiting outreach clinics. GPs form the day-to-day interface:

Routine monitoring bloods and hydroxyurea dose review
Vaccination and penicillin prophylaxis maintenance
Folic acid prescriptions
Acute pain management and fever triage
Screening for end-organ complications (nephropathy, retinopathy, pulmonary hypertension)

Kidney Health Australia guidance on SCD nephropathy: annual urine ACR and creatinine; proteinuria ≥300 mg/g indicates nephropathy; refer nephrology + haematology jointly.

Annual review checklist

Each year:

Hb and reticulocyte count (compare to baseline)
Creatinine and urinalysis (haematuria, proteinuria)
LFTs and bilirubin
Ferritin (iron overload in transfused patients)
Blood pressure (SCD-related hypertension)
Ophthalmology review (sickle cell retinopathy — proliferative in HbSC)
Transcranial Doppler (TCD) in children under 16: high TCD velocity (≥200 cm/s) identifies stroke risk and is an indication to intensify treatment or transfusion programme
Vaccination and penicillin status
Hydroxyurea monitoring bloods and adherence
Psychosocial assessment — depression, anxiety, school/work impacts

E. Special populations

Children. Functional asplenia and stroke risk are most critical in the paediatric age group. Penicillin prophylaxis from age 3 months is standard; TCD screening from age 2 onwards. The BABY HUG trial supports starting hydroxyurea early in childhood regardless of severity.

Pregnancy. SCD in pregnancy carries significant risk: maternal complications (VOC exacerbation, ACS, gestational hypertension, preeclampsia), foetal complications (intrauterine growth restriction, preterm birth, stillbirth). Hydroxyurea is contraindicated in pregnancy. Management is shared between haematology and obstetrics at a centre experienced in high-risk obstetrics. Contraception counselling is essential for all reproductive-age women.

Older adults and chronic organ damage. With improved survival, SCD patients increasingly develop chronic complications: CKD, pulmonary hypertension (right heart catheterisation if suspected), avascular necrosis of femoral heads, leg ulcers, and cognitive decline from cerebrovascular disease. These require multidisciplinary management.

Refugees and newly arrived migrants. Many Australians with SCD arrive from regions without established haematology care. They may have never received hydroxyurea, may be unvaccinated for encapsulated organisms, and may not know their full genotype. A comprehensive haematology referral and catch-up vaccination schedule is essential.

When to escalate

Emergency (same-day ED/hospital):

Fever ≥38.5 °C with any sign of systemic illness — sepsis is a medical emergency in SCD
Acute chest syndrome: new chest infiltrate + fever and/or respiratory symptoms
Any neurological symptom — stroke emergency
Sudden severe anaemia (drop from baseline ≥20 g/L)
Splenic enlargement with shock signs
Priapism lasting >2 hours

Urgent haematology referral:

New diagnosis or suspected diagnosis
Frequent crises (≥3/year) — review hydroxyurea dose
Worsening anaemia or unexplained ferritin rise
New proteinuria or rising creatinine
Suspected pulmonary hypertension

What this article is and is not

This is general health information drawn from current Australian general practice guidelines — eTG, AMH, Australian Immunisation Handbook, RACGP, Kidney Health Australia — and major SCD trials (MSH, BABY HUG, Steinberg follow-up, ASH 2020). It is not personal medical advice and does not create a doctor–patient relationship. Decisions about hydroxyurea dosing, transfusion thresholds, and crisis management plans are made with the patient’s haematologist.

For Australian consumer resources: HealthDirect — Sickle cell anaemia, Better Health Channel.

For acute emergencies: present to the nearest emergency department and inform triage that the patient has sickle cell disease and is functionally asplenic.

Sources cited

Frequently asked questions

What causes the pain in sickle cell crisis?

Vaso-occlusive crisis (VOC) occurs when deoxygenated haemoglobin S polymerises, deforming red blood cells into a rigid crescent shape. These abnormal cells obstruct small vessels, causing ischaemia in bone marrow, muscles, and organs. Pain is typically severe, acute, and affects the long bones, back, chest, and abdomen. It is often described as the worst pain imaginable. Triggers include dehydration, cold exposure, infection, psychological stress, hypoxia, and exertion. Not every crisis has a clear precipitant. Pain assessment should use validated tools (numerical rating scale or FACES for children). Undertreating sickle pain is a major problem — GPs should treat with the same urgency as other severe acute pain.
Who is at risk of sickle cell disease in Australia?

SCD is most prevalent in people of Sub-Saharan African origin (particularly West African countries — Nigeria, Ghana, Sudan, South Sudan, Somalia), Middle Eastern origin, Indian subcontinent (especially Gujarat), and Mediterranean ancestry (southern Italy, Greece, Turkey). Australia's growing ATSI and refugee populations from Sub-Saharan Africa mean SCD is increasingly encountered in general practice outside specialist centres. The sickle cell trait (HbAS) — one copy — is generally benign but important for genetic counselling. Newborn screening for haemoglobinopathies is conducted in all Australian states and territories and most states include SCD.
Is hydroxyurea safe for long-term use?

Yes. Hydroxyurea (hydroxycarbamide) has over 30 years of clinical evidence supporting safety and efficacy. The landmark MSH trial showed ~50% reduction in painful crises, and the Steinberg 17.5-year follow-up demonstrated no increase in cancer risk and significant survival benefit. It works by increasing foetal haemoglobin (HbF), which inhibits HbS polymerisation. In Australia it is PBS-listed for SCD, typically initiated by a haematologist. Monitoring: FBC every 2–4 weeks during dose titration, then 3-monthly when stable; aim for mild leucopenia (WBC 5–8 × 10⁹/L) as a marker of adequate dosing without toxicity. Contraindicated in pregnancy.
What vaccinations does a person with sickle cell disease need?

People with SCD have functional asplenia — the spleen is progressively destroyed by repeated infarction — making them highly susceptible to encapsulated bacterial infections (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis). The Australian Immunisation Handbook and ATAGI recommend: Prevenar 20 (or Prevenar 13 + PPSV23) pneumococcal; MenACWY + MenB meningococcal; Hib; annual influenza; COVID-19 boosters. Lifelong penicillin V prophylaxis (250–500 mg BD) is recommended from diagnosis through to at least age 5, and often lifelong in practice in adults who have had splenectomy or functional asplenia. Advise patients to carry an asplenia card.
When does a sickle cell pain crisis need emergency care?

Most acute pain crises in adults without complications can be managed at home or in a GP setting with oral opioids and hydration, if there is a clear plan in place. Emergency presentation is required for: severe pain not controlled by home management plan within 1–2 hours; fever ≥38.5 °C with acute illness (risk of sepsis — constitutes a medical emergency); acute chest syndrome (new infiltrate on CXR + respiratory symptoms); neurological symptoms (stroke — emergency exchange transfusion); priapism lasting >2 hours; acute abdomen (splenic sequestration, cholecystitis); severe anaemia below patient's baseline. GPs should have a written crisis management plan for each patient and know which haematology unit the patient is attached to.

Source quality

Sources grouped by evidence tier. AU primary tier first; international where AU is silent or lagging; named-author reconstruction where guidelines have not yet caught up. How tiers work.