📋 Key Information Summary
- Haemolytic anaemia results from premature destruction of red blood cells (RBCs), either intravascular or extravascular, leading to compensatory reticulocytosis and characteristic laboratory derangements.
- Classic clinical clues include jaundice (scleral icterus), dark urine (haemoglobinuria or bilirubinuria), splenomegaly, fatigue, and pallor — symptoms overlap with other causes of anaemia and require laboratory confirmation.
- The hallmark laboratory tetrad of haemolysis is: ↑ reticulocyte count, ↑ lactate dehydrogenase (LDH), ↓ haptoglobin, and ↑ unconjugated (indirect) bilirubin.
- A peripheral blood film is essential and should be examined early — it may reveal spherocytes (autoimmune haemolytic anaemia), schistocytes (microangiopathic haemolytic anaemia/TTP-HUS), sickle cells, or bite cells (G6PD deficiency).
- The direct antiglobulin test (DAT, Coombs test) is the pivotal first-line investigation to distinguish immune from non-immune haemolysis; a positive DAT suggests autoimmune haemolytic anaemia (AIHA) or drug-induced haemolysis.
- Drug-induced haemolysis is an under-recognised cause in Australian practice — always review the medication chart, including over-the-counter and herbal preparations, when DAT is positive.
- G6PD deficiency should be considered in patients of Mediterranean, South-East Asian, Middle Eastern, or African ancestry who present with acute haemolysis triggered by infection, oxidant drugs (e.g., dapsone, primaquine, sulfonamides), or fava beans.
- Haemoglobin electrophoresis is indicated when the peripheral film shows target cells, polychromasia with microcytosis, or there is a family history of haemoglobinopathy.
- Urgent haematology referral is required for rapid haemoglobin drop (>20 g/L over 24–48 hours), haemodynamic instability, suspected thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS), severe AIHA unresponsive to initial corticosteroids, or haemolysis of unclear aetiology with significant anaemia.
- TTP/HUS is a medical emergency — do not wait for referral confirmation before initiating plasma exchange if clinically suspected; delay in treatment is associated with mortality exceeding 90% if untreated.
- Intravenous immunoglobulin (IVIg) and rituximab are second-line agents in refractory AIHA; splenectomy is reserved for steroid-dependent or resistant cases.
- Aboriginal and Torres Strait Islander peoples may present with higher rates of infection-related haemolysis (e.g., malaria, Clostridium perfringens sepsis) and require culturally sensitive assessment, awareness of remote-area access barriers, and timely transfer when urgent referral is indicated.
Introduction & Australian Epidemiology
Haemolytic anaemia encompasses a heterogeneous group of disorders characterised by the accelerated destruction of red blood cells (RBCs), with a resultant decrease in RBC lifespan from the normal ~120 days to as short as a few days. Haemolysis may be classified by the primary site of RBC destruction — intravascular (within the circulation) or extravascular (within the reticuloendothelial system, predominantly the spleen and liver) — or by aetiology as either inherited or acquired.
In Australia, the most commonly encountered causes of haemolytic anaemia in primary care and emergency settings include:
- Autoimmune haemolytic anaemia (AIHA): Incidence approximately 1–3 per 100,000 per year; warm AIHA (IgG-mediated) is most common, with cold agglutinin disease (IgM-mediated) comprising ~15–20% of cases.
- Haemolytic disease of the fetus and newborn (HDFN): Largely prevented by anti-D immunoglobulin (RhoGAM) prophylaxis, but remains relevant in unsensitised mothers and in non-Rh(D) antigen incompatibility (e.g., Kell, Duffy).
- G6PD deficiency: Present in ~4–5% of the Australian population of Mediterranean, South-East Asian, Middle Eastern, and African descent. Often unrecognised until an oxidant stress triggers acute haemolysis.
- Sickle cell disease and thalassaemia: Increasingly prevalent due to immigration; haemoglobinopathies are now among the most common genetic conditions managed in Australian haematology clinics.
- Microangiopathic haemolytic anaemia (MAHA): Including TTP, HUS, HELLP syndrome, and disseminated intravascular coagulation (DIC) — all requiring urgent recognition and management.
- Infection-associated haemolysis: Including malaria (relevant in returned travellers and some Northern Territory communities), Clostridium perfringens, and babesiosis.
- Mechanical/prosthetic valve haemolysis: Seen in patients with prosthetic heart valves or after cardiac surgery.
The Australian Institute of Health and Welfare (AIHW) reports that anaemia accounts for a significant proportion of hospital presentations in Aboriginal and Torres Strait Islander populations, with haemolysis from infection and nutritional deficiency contributing disproportionately. Access to timely haematology specialist services remains limited in rural and remote areas, underscoring the importance of systematic primary-care evaluation before referral.
Clinical red flag: Any patient presenting with a rapid, unexplained drop in haemoglobin combined with jaundice, dark urine, or new-onset splenomegaly should be assumed to have haemolytic anaemia until proven otherwise. Do not attribute the anaemia to chronic disease or iron deficiency without excluding haemolysis first.
Clinical & Laboratory Clues
The clinical presentation of haemolytic anaemia is variable and depends on the rate and mechanism of haemolysis (acute versus chronic, intravascular versus extravascular), the degree of compensatory erythropoiesis, and the underlying aetiology. The following clinical and laboratory features should raise suspicion for haemolysis.
Clinical Features
| Feature | Mechanism | Clinical Context |
|---|---|---|
| Jaundice / scleral icterus | Elevated unconjugated bilirubin from RBC catabolism exceeds hepatic conjugation capacity | Most prominent in acute haemolysis; may be subtle in chronic compensated haemolysis |
| Dark urine | Haemoglobinuria (intravascular haemolysis) or bilirubinuria (conjugated bilirubin overload) | Intravascular haemolysis (e.g., PNH, march haemoglobinuria, severe transfusion reaction); urine dipstick positive for blood but no RBCs on microscopy |
| Splenomegaly | Extravascular haemolysis and RBC sequestration in the spleen | Common in hereditary spherocytosis, AIHA, thalassaemia, myeloproliferative disorders |
| Fatigue, pallor, dyspnoea | Tissue hypoxia from reduced oxygen-carrying capacity | Non-specific; severity correlates with degree and rapidity of haemoglobin drop |
| Leg ulcers | Chronic severe haemolysis with impaired tissue oxygenation | Sickle cell disease, severe hereditary spherocytosis, PNH |
| Bone pain / skeletal changes | Compensatory marrow expansion (erythroid hyperplasia) | Thalassaemia major, sickle cell disease; "crew cut" skull X-ray appearance |
| Gallstones (pigment type) | Chronic excess bilirubin excretion leading to calcium bilirubinate gallstones | Chronic haemolytic states; may present in childhood in hereditary spherocytosis |
Laboratory Clues — The Haemolysis Panel
A systematic "haemolysis screen" should be requested when clinical suspicion exists. The following laboratory abnormalities are characteristic:
| Parameter | Expected Finding | Interpretation |
|---|---|---|
| Reticulocyte count | ↑↑ Elevated (often >100 × 10⁹/L; reticulocyte % >2%) | Reflects compensatory bone marrow response; low retic count in the setting of haemolysis suggests marrow failure (aplastic crisis, parvovirus B19) |
| Lactate dehydrogenase (LDH) | ↑↑ Elevated (often >500 U/L; may exceed 1000 U/L in severe haemolysis) | Released from lysed RBCs; highly sensitive but non-specific (also elevated in liver disease, malignancy, myocardial infarction) |
| Haptoglobin | ↓↓ Low or undetectable (<0.3 g/L) | Binds free haemoglobin; depleted in both intravascular and significant extravascular haemolysis. Most specific single marker. May be low in liver disease or congenital absence |
| Unconjugated (indirect) bilirubin | ↑ Elevated (>17 µmol/L; often 30–80 µmol/L) | Product of haem catabolism; conjugated fraction should remain normal or low in pure haemolysis |
| Haemoglobin | ↓ Variable — may be near-normal in chronic compensated haemolysis or rapidly falling in acute haemolysis | Trend is more informative than a single value; serial FBC monitoring is essential |
| Peripheral blood film | Polychromasia, spherocytes, schistocytes, bite cells, sickle cells, target cells, agglutination | Critical for aetiological clues; should be reviewed by an experienced haematologist or morphologist |
Pearl: Haptoglobin is the most sensitive and specific single marker for haemolysis. A normal haptoglobin level in the setting of suspected haemolysis makes active significant haemolysis unlikely. However, haptoglobin is an acute phase reactant and may be falsely elevated in inflammatory states — interpret alongside LDH and reticulocyte count.
Important: Reticulocytes have a higher MCV than mature RBCs. A raised MCV in the setting of haemolysis does not necessarily indicate concurrent B12/folate deficiency — it may simply reflect reticulocytosis. Measure the corrected reticulocyte count (reticulocyte % × patient Hb / normal Hb) to assess true marrow response adequacy.
Confirming Haemolysis
Once clinical suspicion exists, a systematic laboratory approach confirms the diagnosis and directs further investigation. The following stepwise approach is recommended for Australian practice.
1
Full Blood Count (FBC) with Film
Confirm anaemia (Hb below age/sex reference range). Review the blood film for morphological clues — spherocytes, schistocytes, bite cells, target cells, polychromasia, red cell agglutination. Request the laboratory to comment on red cell morphology explicitly.
2
Reticulocyte Count
An absolute reticulocyte count >100 × 10⁹/L (or reticulocyte % >2–3%) indicates appropriate marrow response to RBC loss. Calculate the corrected reticulocyte count to assess whether the marrow response is adequate for the degree of anaemia. A low reticulocyte count in the setting of haemolysis is a red flag for marrow failure (e.g., parvovirus B19 aplastic crisis).
3
Haemolysis Biochemistry Panel
Request simultaneously: LDH, haptoglobin, and unconjugated (indirect) bilirubin. This triad, together with the reticulocyte count and blood film, forms the haemolysis confirmation panel. All four parameters are available through Australian pathology laboratories (MBS item 66551 for reticulocyte count; LDH and bilirubin under standard biochemistry panels).
4
Distinguish Intravascular vs Extravascular Haemolysis
Intravascular haemolysis presents with haemoglobinuria (urine dipstick positive for blood, no RBCs on microscopy), haemoglobinaemia (pink-tinged plasma), and very low haptoglobin (<0.1 g/L). Extravascular haemolysis is more common and features splenomegaly, spherocytes on film, and predominantly unconjugated hyperbilirubinaemia.
Confirmatory Features — Summary Table
| Test | Confirmatory of Haemolysis | MBS Availability |
|---|---|---|
| Reticulocyte count (absolute) | >100 × 10⁹/L (corrected >2%) | MBS 66551 — widely available |
| LDH | >500 U/L (often >1000 in significant haemolysis) | Standard biochemistry panel |
| Haptoglobin | <0.3 g/L or undetectable | MBS 66586 — available at major labs |
| Indirect bilirubin | >17 µmol/L with normal conjugated fraction | Standard biochemistry panel |
| Direct antiglobulin test (DAT) | Positive (to classify as immune-mediated) | MBS 66554 — available at major labs |
| Peripheral blood film | Morphological features as above | Standard haematology request |
Parvovirus B19 aplastic crisis: If a patient with known chronic haemolytic anaemia presents with a sudden, severe drop in haemoglobin and a LOW reticulocyte count, suspect parvovirus B19-induced transient aplastic crisis. This requires urgent supportive care (transfusion) and infection control measures (airborne precautions as per ACSQHC guidelines).
First-Line Etiologic Tests
Once haemolysis is confirmed, the next step is to determine the underlying cause. This is guided by the direct antiglobulin test (DAT), the peripheral blood film, clinical history, and targeted investigations. The following algorithmic approach is recommended.
Direct Antiglobulin Test (DAT) — The Pivotal Test
The DAT detects antibody (IgG) or complement (C3d) bound to the surface of the patient's RBCs. It should be requested in all cases of confirmed haemolysis where the cause is not immediately apparent.
DAT Positive
Suggests immune-mediated haemolysis:
- Warm AIHA (IgG positive ± C3d): Most common type; idiopathic, or secondary to SLE, lymphoproliferative disorders, drugs. Spherocytes on film.
- Cold agglutinin disease (C3d positive only): IgM-mediated; triggered by Mycoplasma pneumoniae infection or EBV; associated with intravascular haemolysis in cold temperatures.
- Drug-induced haemolysis: Review all medications — common culprits include methyldopa, penicillins, cephalosporins, cephalosporins (especially ceftriaxone), piperacillin-tazobactam, NSAIDs, quinidine, and dapsone.
- Haemolytic transfusion reaction: Occurs within hours of transfusion; always cross-check blood bank records.
DAT Negative
Suggests non-immune haemolysis:
- Microangiopathic (MAHA): Schistocytes on film — consider TTP, HUS, DIC, HELLP, prosthetic valve haemolysis, malignant hypertension. Check platelet count, coagulation (INR/APTT/fibrinogen), ADAMTS13 activity.
- Intracorpuscular defects: Hereditary spherocytosis, G6PD deficiency, haemoglobinopathies (sickle cell, thalassaemia), PNH. Target specialised tests as below.
- Infection: Malaria (thick and thin film), Clostridium perfringens, Babesia. Send malaria screen (MBS 69313) if relevant exposure history.
- Mechanical: March haemoglobinuria, cardiopulmonary bypass, extracorporeal circuits.
- Toxins/oxidants: Snake envenomation, copper toxicity (Wilson's disease), lead poisoning.
Targeted Etiologic Investigations
Essential
DAT (Coombs test) — IgG and C3d
First-line test in all unexplained haemolysis. Available at all major Australian pathology services. MBS 66554. If negative but clinical suspicion high, request DAT on a fresh sample (false negatives can occur with IgG subclass, low-affinity antibodies, or technical factors).
Essential
Peripheral blood film — expert morphologist review
Request explicit morphological commentary. Spherocytes (AIHA, hereditary spherocytosis), schistocytes (MAHA), bite cells/Heinz bodies (G6PD), target cells (haemoglobinopathy), agglutination (cold agglutinin disease). Available at all Australian pathology labs.
Available
G6PD enzyme assay
MBS 66596. Essential when G6PD deficiency is suspected (Mediterranean, South-East Asian, Middle Eastern, or African ancestry; acute haemolysis after oxidant drug exposure). Note: G6PD levels may be falsely normal during acute haemolysis (young RBCs have higher enzyme activity) — repeat 6–8 weeks after the acute episode for definitive diagnosis.
Available
Haemoglobin electrophoresis / HPLC
MBS 66578. Indicated when blood film shows target cells, microcytosis with elevated RBC count, or when there is a family history or ethnic background suggestive of haemoglobinopathy (sickle cell disease, thalassaemia). Available at major pathology networks (Sullivan Nicolaides, Douglass Hanly Moir, Laverty).
Available
Osmotic fragility / eosin-5-maleimide (EMA) binding test
For hereditary spherocytosis confirmation. EMA flow cytometry is the preferred test (higher sensitivity and specificity than osmotic fragility). Available at specialist haematology reference labs.
Available
ADAMTS13 activity
Essential when TTP is suspected (schistocytes + thrombocytopenia ± neurological/renal symptoms). Available through state reference laboratories — results may take 24–72 hours. DO NOT delay plasma exchange while awaiting results if clinical suspicion is high.
Available
Infection screen
Malaria thick/thin film (MBS 69313), blood cultures, Mycoplasma pneumoniae serology, EBV serology, parvovirus B19 IgM/PCR, hepatitis serology. Guided by clinical context and exposure history.
Available
Flow cytometry for PNH (CD55, CD59)
Indicated when there is intravascular haemolysis with dark urine, iron deficiency, thrombosis (especially Budd-Chiari syndrome), or pancytopenia. Available at major haematology centres.
Referral
Direct bilirubin / urine haemosiderin
Urine haemosiderin (Prussian blue stain of urinary sediment) indicates chronic intravascular haemolysis — useful for PNH monitoring. Available at reference labs.
Drug-Induced Haemolysis — Key Considerations
Drug-induced haemolytic anaemia is an important and potentially reversible cause. It should be suspected whenever the DAT is positive and there is a temporal relationship with medication initiation. Common mechanisms include:
- Drug adsorption (hapten) mechanism: High-dose penicillins, cephalosporins — antibody binds to drug adsorbed on RBC surface.
- Immune complex mechanism: Quinidine, sulfonamides — drug-antibody complexes bind RBCs and activate complement.
- Autoantibody induction: Methyldopa, fludarabine — drug induces true autoantibodies against RBC antigens.
- Non-immune oxidative damage: Dapsone, rasburicase, primaquine — direct RBC oxidant injury (DAT negative).
Dapsone in Australian practice: Dapsone is used for dermatitis herpetiformis, Pneumocystis jirovecii prophylaxis (common in immunocompromised patients), and leprosy treatment. It causes dose-dependent oxidative haemolysis, particularly in G6PD-deficient patients. Always check G6PD status before initiating dapsone. Available as authority-required PBS item.
Urgent Referral Triggers
Certain presentations of haemolytic anaemia require urgent haematology referral, emergency department presentation, or both. The following triggers mandate immediate action.
Routine Referral
Stable Chronic Haemolysis
Mild anaemia (Hb >100 g/L) with stable reticulocyte count, no haemodynamic compromise, and identifiable cause (e.g., known hereditary spherocytosis, stable AIHA on treatment).
Setting: Outpatient haematology referral within 1–2 weeks
Semi-Urgent
Progressive or Unexplained Haemolysis
Hb 70–100 g/L with ongoing haemolysis, newly diagnosed AIHA starting corticosteroids, DAT-negative haemolysis of uncertain cause, or haemolysis in a patient with significant comorbidities.
Setting: Urgent outpatient haematology review within 24–72 hours; consider ED if deteriorating
Emergency
Life-Threatening Haemolysis
Rapid Hb drop (>20 g/L in 24–48 h), Hb <70 g/L with symptoms, haemodynamic instability (tachycardia, hypotension, syncope), suspected TTP/HUS (schistocytes + thrombocytopenia + organ dysfunction), severe AIHA unresponsive to initial steroids, acute haemoglobinuric renal failure, or suspected acute transfusion reaction.
Setting: Emergency department presentation; immediate haematology consultation; consider ICU/HDU
Specific Urgent Scenarios
TTP/HUS — Medical Emergency: Suspect TTP when there is MAHA (schistocytes on film), thrombocytopenia (<150 × 10⁹/L), neurological symptoms (confusion, headache, seizures), renal impairment, and fever — the classic pentad. ADAMTS13 activity <10% confirms TTP but results take 24–72 hours. Do not wait for confirmatory results. Initiate urgent plasma exchange (plasmapheresis) as soon as TTP is suspected. Contact your state haematology/ transfusion medicine specialist immediately. Corticosteroids (methylprednisolone 1 g IV daily for 3 days) should be co-administered. Caplacizumab (Cablivi®) is now available in Australia as adjunctive therapy under authority prescription (PBS Authority Required) for acquired TTP.
Severe AIHA with haemodynamic compromise: If Hb is <60 g/L or there is haemodynamic instability, do not delay transfusion while awaiting full crossmatch compatibility. In life-threatening AIHA, issue group-compatible (or least incompatible) blood with haematologist consultation. Simultaneously commence methylprednisolone 1 mg/kg IV (or equivalent). Contact the Australian Red Cross Lifeblood serology laboratory for complex serological assistance (13 RED CROSS / 13 73 27).
Quick Referral Decision Aid
Rapid Hb drop (>20 g/L in 24–48 h)
Steroids if immune; supportive care
Same-day haematology / ED
Check FBC q6–12h; crossmatch urgently
TTP/HUS suspected
Plasma exchange + methylprednisolone
Immediate ED / ICU
Do not wait for ADAMTS13 results
Severe AIHA (Hb <60 g/L)
Methylprednisolone 1 mg/kg IV + transfusion
Immediate ED
Issue least-incompatible blood; contact Lifeblood
Acute transfusion reaction
Stop transfusion; IV fluids; supportive
Immediate
Return blood product to blood bank; report to TGA
Unclear cause with significant haemolysis
Supportive; empirical steroids if immune suspected
Semi-urgent haematology (24–72 h)
Complete haemolysis screen before referral
Pre-Referral Workup — What to Order Before Referring
To expedite specialist assessment, the following should be completed before or concurrent with referral:
- FBC with differential and reticulocyte count
- Blood film with explicit morphological commentary
- LDH, haptoglobin, unconjugated bilirubin, conjugated bilirubin
- DAT (IgG and C3d)
- Group and screen / crossmatch if Hb <80 g/L or rapidly falling
- Coagulation studies (INR, APTT, fibrinogen) if MAHA suspected
- Renal function (eGFR, urine microscopy for haemoglobinuria)
- Full medication review — list all current and recently ceased medications
- Infection screen as clinically indicated (malaria screen, blood cultures, parvovirus B19)
Initial Management Principles
While awaiting definitive etiologic diagnosis and specialist input, the following general management principles apply.
Supportive Care
- Transfusion: Red cell transfusion is indicated for symptomatic anaemia (Hb typically <70 g/L, or <80 g/L in patients with cardiorespiratory comorbidities). Use restrictive transfusion thresholds where possible per NHMRC/Australian Red Cross Lifeblood guidelines. In AIHA, crossmatching may be difficult — consult the blood bank and haematologist for least-incompatible units.
- Folic acid supplementation: 5 mg PO daily should be prescribed for all patients with active haemolysis to support increased erythropoiesis and prevent megaloblastic crisis from folate depletion. PBS General Benefit.
- Iron supplementation: Generally NOT required in extravascular haemolysis (iron is recycled). However, chronic intravascular haemolysis (e.g., PNH, mechanical valve) causes urinary iron loss and may lead to iron deficiency — check ferritin and transferrin saturation.
- VTE prophylaxis: AIHA and TTP are prothrombotic states. Ensure appropriate thromboprophylaxis unless contraindicated by active bleeding or severe thrombocytopenia.
- Renal protection: Maintain hydration to prevent haemoglobinuric acute kidney injury in intravascular haemolysis. Monitor urine output and renal function closely.
First-Line Treatment of Warm AIHA
Prednisolone
Solone® · Generic · Corticosteroid
Adult dose
1 mg/kg/day PO (typically 60–80 mg/day) for 1–3 weeks, then taper over 3–6 months once haemolysis controlled
Paediatric dose
1–2 mg/kg/day PO (max 60 mg/day)
Route
PO (IV methylprednisolone equivalent if unable to take oral)
Duration
Initial course 1–3 weeks, then slow taper over 3–6 months
Renal adjustment
None required
Hepatic adjustment
Use with caution; monitor LFTs
PBS status
✔ PBS General Benefit
Rituximab
MabThera® · Biosimilars available · Anti-CD20 monoclonal antibody
Adult dose
375 mg/m² IV weekly × 4 weeks (or 1000 mg IV days 1 and 15)
Indication
Second-line for steroid-refractory or steroid-dependent warm AIHA
Route
IV infusion (under specialist supervision)
Renal adjustment
None required
Hepatic adjustment
None required
PBS status
⚠ PBS Authority Required — for refractory AIHA
Cold agglutinin disease management: Unlike warm AIHA, cold agglutinin disease responds poorly to corticosteroids and splenectomy. First-line management is cold avoidance (warm clothing, avoid cold environments), with rituximab (± bendamustine) as the preferred disease-modifying therapy under haematologist supervision. Supportive transfusion with a blood warmer is essential.
Special Populations
Pregnancy
- AIHA in pregnancy: Prednisolone is the safest first-line agent; it is metabolised by the placenta (minimal fetal exposure). Rituximab should be avoided, especially in the first trimester.
- Haemolytic disease of the fetus/newborn (HDFN): Monitor with regular antibody titres (anti-D, anti-Kell, etc.) and middle cerebral artery peak systolic velocity (MCA-PSV) Doppler. Refer to maternal-fetal medicine specialist.
- HELLP syndrome: A form of MAHA occurring in the third trimester (usually with pre-eclampsia). Requires urgent obstetric review and delivery is the definitive treatment.
- G6PD in pregnancy: Avoid oxidant drugs (nitrofurantoin, sulfonamides) — these are commonly prescribed for UTI prophylaxis in pregnancy.
All cases of haemolysis in pregnancy should be co-managed with obstetric medicine and haematology.
Paediatrics
- Neonatal jaundice: Severe unconjugated hyperbilirubinaemia from haemolysis (ABO/Rh incompatibility, hereditary spherocytosis) may cause kernicterus — urgent phototherapy and exchange transfusion thresholds apply per ANZNN guidelines.
- Hereditary spherocytosis: Often presents in infancy with jaundice and anaemia. Avoid splenectomy before age 5–6 years due to overwhelming post-splenectomy infection risk. Vaccinate against encapsulated organisms (meningococcus, pneumococcus, H. influenzae) before splenectomy.
- Childhood AIHA: Often post-viral, self-limiting. Prednisolone 2 mg/kg/day is first-line. Most children achieve remission within 3–6 months.
- Thalassaemia: Increasingly common in Australian paediatric populations due to immigration from endemic regions. Specialist haemoglobinopathy clinics are available in major paediatric centres (e.g., RCH Melbourne, Westmead Children's Hospital Sydney).
Elderly
- Cold agglutinin disease is predominantly a disease of the elderly (median age >60 years) and may present insidiously with chronic fatigue and mild jaundice.
- Drug-induced haemolysis is more common due to polypharmacy — always conduct a thorough medication review.
- Lymphoproliferative disorders: In older adults, AIHA may be secondary to chronic lymphocytic leukaemia (CLL) or lymphoma — always consider underlying malignancy.
- Corticosteroid side effects (osteoporosis, diabetes, infection risk) are amplified in the elderly — use the lowest effective dose and plan early steroid-sparing strategies.
Renal Impairment
- Haemoglobinuria from intravascular haemolysis can cause acute tubular necrosis — maintain aggressive IV hydration (aim UO >0.5 mL/kg/h) and monitor renal function closely.
- HUS predominantly affects the kidneys — early involvement of nephrology is essential.
- Erythropoietin requirements may change in patients with CKD who develop haemolysis — reassess ESA dosing.
Hepatic Impairment
- Liver disease can independently cause spur-cell anaemia (acanthocytosis) and pseudo-haemolytic anaemia with elevated LDH and bilirubin — distinguishing true haemolysis from liver-related artefact can be challenging.
- Wilson's disease should be considered in young patients with Coombs-negative haemolysis and liver dysfunction — check caeruloplasmin and 24-hour urinary copper.
- Prednisolone dosing may need adjustment in severe hepatic impairment; dexamethasone (which does not require hepatic activation) may be preferred.
Immunocompromised
- HIV: Multiple causes of haemolysis including drugs (dapsone, TMP-SMX for PJP prophylaxis), infection (Babesia, CMV), and immune-mediated mechanisms. Check G6PD before dapsone.
- Post-transplant: Donor-recipient ABO mismatch can cause passenger lymphocyte syndrome (a form of AIHA presenting 1–3 weeks post-transplant).
- Fludarabine: Can induce severe, life-threatening AIHA — avoid in patients with pre-existing AIHA and monitor FBC closely during treatment.
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
📚 References
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