📋 Key Information Summary
- Immune thrombocytopenia (ITP) is an autoimmune disorder characterised by isolated thrombocytopenia (platelet count <100 × 10⁹/L) in the absence of other causes of thrombocytopenia — it is a diagnosis of exclusion.
- Primary mechanism: IgG autoantibodies (predominantly against GPIIb/IIIa and GPIb/IX) opsonise platelets for Fc-receptor-mediated splenic destruction; impaired megakaryopoiesis contributes in most patients.
- Incidence in Australia is approximately 3.3 per 100 000 adults per year; children 1.9–6.4 per 100 000, with a male:female ratio approaching 1:1 in adults but slight male predominance in children.
- Clinical presentation ranges from incidental asymptomatic thrombocytopenia to life-threatening mucocutaneous and intracranial haemorrhage; platelet count does not always correlate with bleeding risk.
- Treatment is indicated for platelet count <30 × 10⁹/L, significant mucocutaneous bleeding, or prior to procedures — NOT for the count alone when asymptomatic above threshold.
- First-line therapy: corticosteroids — prednis(ol)one 1 mg/kg/day (max 80 mg) PO for 1–2 weeks then taper over 2–4 weeks, OR pulsed dexamethasone 40 mg PO daily × 4 days (1–3 cycles).
- For emergency bleeding or urgent pre-procedural platelet rise: IV immunoglobulin (IVIg) 0.4–1 g/kg over 1–5 days ± platelet transfusion with concurrent IVIg or tranexamic acid.
- Second-line therapy for chronic/refractory ITP: thrombopoietin receptor agonists (TPO-RAs) — romiplostim (SC weekly) or eltrombopag (PO daily) — are PBS Authority Required and achieve response in 60–90% of patients.
- Rituximab (anti-CD20 monoclonal antibody) offers 60% initial response rate but ~50% relapse by 1–2 years; used off-PBS in Australia for steroid-refractory ITP.
- Splenectomy remains curative in ~60–70% but is deferred until ≥12 months of medical therapy and avoided in children <5 years due to overwhelming infection risk.
- Children: 75–80% of paediatric ITP is self-limiting within 6–12 months; watchful waiting appropriate if platelet count >20 × 10⁹/L and no significant bleeding.
- ATSI Australians have higher rates of ITP complications and reduced access to haematology specialist care; engage MBS telehealth item 91822 and ensure culturally safe management.
Introduction & Australian Epidemiology
Immune thrombocytopenia (ITP) is an acquired autoimmune disorder defined by a platelet count below 100 × 10⁹/L in the absence of other identifiable causes of thrombocytopenia. It may present as an isolated haematological finding or as part of a systemic condition. The International Working Group (IWG) standardised terminology in 2009, replacing the older term "idiopathic thrombocytopenic purpura" with "immune thrombocytopenia" to reflect the autoimmune pathogenesis.
In Australia, population-based studies estimate adult ITP incidence at 3.3 per 100 000 per year, with a prevalence of approximately 9.5 per 100 000. Paediatric ITP peaks between ages 2–5 years with an annual incidence of 1.9–6.4 per 100 000. Unlike many autoimmune conditions, adult ITP shows an approximately equal sex distribution, though some series report a slight female preponderance.
ITP is classified as primary (isolated, no associated condition) in approximately 80% of adults and 70% of children, and secondary when associated with conditions such as systemic lupus erythematosus (SLE), antiphospholipid syndrome, chronic lymphocytic leukaemia, hepatitis C, HIV, or Helicobacter pylori infection. Secondary causes must be actively excluded during initial workup.
The disease course is defined as newly diagnosed (<3 months), persistent (3–12 months), or chronic (>12 months). In adults, ~60% become chronic; in children, 75–80% undergo spontaneous remission within 6–12 months, making the prognosis markedly more favourable in the paediatric population.
Mortality in ITP is predominantly driven by bleeding (intracranial haemorrhage rate ~0.1–0.5% overall, but ~5% in refractory severe ITP) and infection (especially post-splenectomy overwhelming infection). A landmark Danish registry study demonstrated increased all-cause mortality in ITP patients compared with the general population (standardised mortality ratio 1.5–2.2), with age, refractory disease, and treatment-related complications as major drivers.
Pathogenesis: Anti-Platelet IgG Antibodies
The pathophysiology of ITP involves a complex interplay of humoral immune dysregulation, cell-mediated cytotoxicity, and impaired thrombopoiesis. The traditional view of ITP as a pure antibody-mediated platelet destruction disorder has evolved into a multi-hit model.
Antibody-Mediated Platelet Destruction
In 50–75% of patients, IgG autoantibodies target platelet surface glycoproteins, most commonly:
- GPIIb/IIIa (integrin αIIbβ3) — the most frequent target (~70% of antibody-positive cases); also expressed on megakaryocytes, so antibodies may directly inhibit platelet production.
- GPIb/IX/V (von Willebrand factor receptor) — second most common (~20–40%); GPIb-directed antibodies may cause Fc-independent platelet clearance via desialylation and hepatic Ashwell–Morell receptor uptake.
- GPIa/IIa (collagen receptor) and GPIV (CD36) — less frequent; present in <10% of cases individually.
Opsonised platelets are cleared predominantly in the spleen by Fcγ receptor-bearing macrophages in the red pulp. The spleen also serves as the major site of autoantibody production by long-lived plasma cells and memory B cells resident in the marginal zone.
Cell-Mediated Immune Mechanisms
Patients seronegative for anti-platelet antibodies (25–50% of ITP patients) have demonstrable T-cell-mediated mechanisms:
- Th1/Th17 skewing with reduced Treg function and expanded cytotoxic CD8⁺ T cells capable of direct platelet and megakaryocyte lysis.
- Reduced production of IL-10 and TGF-β by regulatory T cells, permitting perpetuation of autoimmune responses.
- Increased platelet apoptosis driven by caspase activation, independent of splenic sequestration.
Impaired Thrombopoiesis
Anti-platelet antibodies cross-react with megakaryocyte surface glycoproteins (particularly GPIIb/IIIa and GPIb/IX), inhibiting platelet budding in the bone marrow. Additionally, CD8⁺ T-cell-mediated megakaryocyte apoptosis reduces platelet production. Endogenous thrombopoietin (TPO) levels are only modestly elevated in ITP (unlike aplastic anaemia) because TPO is constitutively produced and catabolised by binding to platelet mass — a smaller platelet mass reduces TPO clearance, but the rise is insufficient to compensate for ongoing destruction.
Clinical pearl: The modest TPO elevation in ITP explains why TPO receptor agonists (romiplostim, eltrombopag) are effective — they pharmacologically supplement the endogenous TPO signal, stimulating residual megakaryopoiesis even in the presence of inhibitory antibodies.
Fcgamma Receptor Polymorphisms
FcγRIIa (CD32) and FcγRIIIa (CD16) polymorphisms influence macrophage phagocytic capacity and have been associated with ITP susceptibility and response to IVIg therapy. The H131 FcγRIIa variant shows higher affinity for IgG1 and IgG2 immune complexes and may predict more aggressive disease.
Clinical Features & Severity
The clinical presentation of ITP varies from an asymptomatic incidental finding to life-threatening haemorrhage. Bleeding severity does not always correlate with platelet count — some patients with platelet counts of 5 × 10⁹/L may have minimal bleeding, while others with counts of 30–40 × 10⁹/L may exhibit significant purpura.
Presentation by Platelet Count
Mild
Platelets 50–100 × 10⁹/L
Often asymptomatic. May have easy bruising, petechiae after minor trauma, or prolonged bleeding after dental extraction. Women may report menorrhagia.
Setting: Outpatient observation, oral surgery clearance with precautions
Moderate
Platelets 20–50 × 10⁹/L
Spontaneous petechiae and ecchymoses. Epistaxis, gingival bleeding, menorrhagia. Increased bruising with minor trauma. Increased bleeding risk with procedures.
Setting: Outpatient with close follow-up; initiate treatment if bleeding
Severe
Platelets <20 × 10⁹/L
Spontaneous mucosal haemorrhage: oral blood blisters (wet purpura), haematuria, GI bleeding, menorrhagia. Risk of intracranial haemorrhage (0.1–0.5% overall, higher with head trauma). Retinal haemorrhage possible.
Setting: Hospital admission; urgent treatment indicated
Bleeding Assessment — ITP Bleeding Score (IBLS)
The ITP Bleeding Score assesses bleeding in 11 anatomical sites (skin, oral, nasal, GI, urinary, gynaecological, CNS, etc.) on a 0–4 scale per site. A total score ≥8 correlates with increased haemorrhagic risk and may prompt escalation of therapy regardless of platelet count.
Associated Findings
- Splenomegaly is typically absent in primary ITP — its presence should prompt investigation for secondary causes (lymphoproliferative disorders, portal hypertension).
- Hepatomegaly or lymphadenopathy suggest a secondary or alternative diagnosis.
- Anaemia may be present from chronic blood loss (iron deficiency) or autoimmune haemolytic anaemia (Evans syndrome — Coombs-positive in ~10–20% of ITP patients).
- Fatigue is increasingly recognised as a significant quality-of-life impairment in ITP, often disproportionate to thrombocytopenia severity and may persist even after platelet count normalisation.
Emergency Presentations
Life-threatening bleeding in ITP: Intracranial haemorrhage, massive GI haemorrhage, or retinal haemorrhage constitute medical emergencies. Management requires simultaneous IVIg (1 g/kg), pulsed corticosteroids (methylprednisolone 1 g IV × 1–3 days), platelet transfusion (with concurrent IVIg to prolong transfused platelet survival), tranexamic acid 1 g IV, and urgent haematology consultation. Consider emergency splenectomy if refractory.
Investigations — Diagnosis of Exclusion
There is no single definitive diagnostic test for ITP. The diagnosis requires demonstration of isolated thrombocytopenia (platelet count <100 × 10⁹/L) on at least two occasions separated by >1 week, with exclusion of all other causes of thrombocytopenia. The IWG 2009 criteria form the basis of Australian diagnostic practice.
Essential Baseline Investigations
Essential
Full blood count (FBC) with blood film
Confirms isolated thrombocytopenia. Blood film review is critical — excludes pseudothrombocytopenia (EDTA clumping), giant platelets (MYH9 disorders, Bernard–Soulier), schistocytes (TTP/HUS, DIC), dysplastic features (MDS), or leukaemic blasts. MBS item 65070.
Essential
Peripheral blood smear (manual review)
Must be reviewed by experienced haematologist or haematology scientist. Giant platelets suggest inherited thrombocytopenia; schistocytes suggest microangiopathic process.
Essential
Reticulocyte count
MBS item 65095. Elevated reticulocytes suggest haemolysis; appropriate reticulocyte response helps assess marrow compensation.
Essential
Direct antiglobulin test (Coombs)
Identifies concurrent autoimmune haemolytic anaemia (Evans syndrome). Positive in ~10–20% of ITP patients. MBS item 65165.
Essential
HIV serology
HIT-recommended screening in all patients with new ITP. HIV-associated thrombocytopenia is treatable and distinction from primary ITP alters management.
Essential
Hepatitis B and C serology
HCV is associated with secondary ITP (prevalence ~20% in HCV cohorts). HBV may cause thrombocytopenia via hypersplenism and marrow suppression. Antiviral treatment of HCV may resolve secondary ITP.
Essential
Helicobacter pylori testing
Urea breath test (MBS item 66707) or stool antigen. H. pylori eradication induces platelet count improvement in ~50% of H. pylori-positive ITP patients, particularly in East Asian and Italian populations; data in Australian populations is less robust but testing is recommended by ISTH.
Essential
Immunoglobulin levels (IgG, IgA, IgM)
Assess for common variable immunodeficiency (CVID) as a secondary cause. Important prior to rituximab therapy, which depletes B cells.
Essential
ANA, dsDNA, antiphospholipid antibodies
Screen for SLE and antiphospholipid syndrome as secondary causes of ITP. Lupus anticoagulant and anticardiolipin/anti-β2-glycoprotein I antibodies should be tested.
Essential
Thyroid function tests
Autoimmune thyroid disease (Hashimoto's, Graves') is associated with ITP in ~15–20% of cases. Hypothyroidism can exacerbate bleeding tendency.
Essential
Renal and liver function, LDH, haptoglobin
Exclude TTP/HUS (elevated LDH, low haptoglobin, schistocytes). Assess hepatic function for secondary portal hypertension and drug-induced thrombocytopenia.
Specialised / Referral Investigations
Referral
Anti-platelet antibody testing (MAIPA assay)
Monoclonal antibody-specific immobilisation of platelet antigens. Sensitivity ~50–70% for GPIIb/IIIa antibodies; specificity ~90%. Not required for diagnosis but may be useful in atypical cases or to distinguish ITP from inherited thrombocytopenia. Available at specialised reference laboratories (e.g., RCPA-registered).
Referral
Bone marrow biopsy
Not routinely required in typical ITP in patients <60 years. Indicated if: age ≥60 years (exclude myelodysplasia), atypical features, treatment failure, prior to splenectomy, or abnormal blood film. Shows increased megakaryocytes with normal myeloid and erythroid lineages.
Referral
Flow cytometry for paroxysmal nocturnal haemoglobinuria (PNH)
Consider if cytopenias are multilineage, raised LDH, or intravascular haemolysis. GPI-anchored protein analysis on granulocytes and red cells.
Specialist
Genetic testing for inherited thrombocytopenias
Consider in persistent isolated thrombocytopenia since childhood, family history, large platelets, or refractory "ITP." Gene panels include MYH9, GP1BA, GP1BB, GP9, ANKRD26, RUNX1. Available via specialist genetics services (Royal Children's Hospital Melbourne, Westmead).
Pitfall: The diagnosis of ITP may be confidently established without bone marrow biopsy in patients aged <60 years with typical clinical features and no atypical findings on blood film. Unnecessary bone marrow aspiration delays treatment initiation and causes patient distress.
Management: Steroids, IVIG, TPO-RA & Rituximab
Treatment decisions in ITP should be individualised based on bleeding severity, comorbidities, lifestyle factors (occupation, sport participation, planned procedures), patient preferences, and platelet count. The primary therapeutic goal is to achieve a safe platelet count (typically >30 × 10⁹/L and absence of significant bleeding), not necessarily a normal platelet count.
When to Treat
- Platelet count <30 × 10⁹/L in adults — treat regardless of symptoms
- Significant mucocutaneous bleeding at any platelet count
- Platelet count <50 × 10⁹/L with risk factors: anticoagulant therapy, planned surgery, uncontrolled hypertension, active peptic ulcer disease
- Platelet count 30–50 × 10⁹/L without bleeding — may observe with close monitoring
- In children: treatment if platelet count <20 × 10⁹/L with bleeding symptoms, or <10 × 10⁹/L regardless of symptoms
First-Line Therapy
Corticosteroids
Prednis(ol)one
Panafcortelone® · Generic · Corticosteroid
Adult dose
1 mg/kg/day PO (max 80 mg) for 1–2 weeks, then taper over 2–4 weeks to discontinuation. Total duration ≤6 weeks preferred.
Paediatric dose
1–2 mg/kg/day PO for 1–2 weeks; taper over 2–3 weeks. Dexamethasone 0.6 mg/kg/day × 4 days as alternative.
Route / frequency
Oral, once daily (morning)
Renal adjustment
No dose adjustment required; monitor fluid retention
Hepatic adjustment
No dose adjustment; hepatotoxicity monitoring recommended
PBS status
✔ PBS General Benefit
Dexamethasone (pulsed)
Generic · Corticosteroid (high-dose pulse)
Adult dose
40 mg PO daily × 4 days. Repeat 1–3 cycles at 14–28 day intervals if initial response then relapse.
Paediatric dose
0.6 mg/kg/day (max 40 mg) PO × 4 days. Limited evidence; prednisolone preferred in most Australian paediatric centres.
Route / frequency
Oral, once daily × 4 days per cycle
Renal adjustment
No adjustment required
PBS status
✔ PBS General Benefit
Evidence note: The RITP trial (Mithoowani et al., Blood 2020) demonstrated that pulsed dexamethasone achieves higher initial response rates (~80% vs ~60%) compared with standard prednisone, but sustained response rates are similar. The 2019 American Society of Hematology (ASH) guidelines conditionally recommend standard-dose prednisone over pulsed dexamethasone; however, Australian haematologists commonly use dexamethasone pulse therapy given the rapid onset and avoidance of prolonged steroid exposure.
IV Immunoglobulin (IVIg)
IV Immunoglobulin
Intragam® P · Privigen® · Normal human immunoglobulin
Adult dose
1 g/kg as single dose OR 0.4 g/kg/day × 5 days. Onset within 24–48 h; duration of response 2–4 weeks.
Paediatric dose
0.8–1 g/kg as single dose (preferred) OR 0.4 g/kg/day × 5 days. Onset within 24–48 hours.
Indications
Emergency bleeding, pre-procedural rapid platelet rise (<24 h needed), corticosteroid contraindication, pregnancy
Renal adjustment
Use with caution in CKD; sucrose-containing preparations contraindicated in severe renal impairment (osmotic nephrosis risk). Intragam P is glycine-stabilised and preferred.
PBS status
⚠ Authority Required — under National Blood Authority (NBA) arrangements. Requires haematologist authorisation.
IVIg supply constraint: Australia is periodically affected by global IVIg supply shortages due to reduced plasma collections. During shortage, the National Blood Authority may restrict IVIg to life-threatening bleeding and emergency surgical procedures only. Subcutaneous immunoglobulin (SCIG) is not established for ITP treatment. Consult local haematology department for current allocation protocols.
Second-Line Therapy
Second-line agents are indicated when patients have persistent or chronic ITP (≥3–6 months duration) and meet any of: platelet count persistently <30 × 10⁹/L despite first-line therapy, recurrent significant bleeding, intolerable steroid side effects, or need for ongoing therapy to maintain safe counts.
Thrombopoietin Receptor Agonists (TPO-RAs)
Romiplostim
Nplate® · Peptibody TPO-RA
Adult dose
Start 1 mcg/kg SC once weekly. Titrate by 1 mcg/kg/week (max 10 mcg/kg) to maintain platelets 50–200 × 10⁹/L. Assess platelet count weekly during titration, then monthly.
Paediatric dose
≥1 year: Start 1 mcg/kg SC weekly. Titrate as per adult protocol. Taper after 6–12 months in responders to assess for sustained remission.
Efficacy
Platelet response (>50 × 10⁹/L) in 79–92% of patients; durable response (≥25 of last 4 weeks) in 38–56%. Post-cessation sustained remission in ~25–30%.
Key risks
Thromboembolism (2–5%), bone marrow reticulin fibrosis (reversible on cessation), rebound thrombocytopenia on abrupt discontinuation
Renal adjustment
No dose adjustment. Safety established in CKD stages 1–5.
PBS status
🔑 Authority Required (Specialist) — Initial 12 weeks authority. Continuing authority requires documented platelet response.
Eltrombopag
Revolade® · Oral non-peptide TPO-RA
Adult dose
Start 50 mg PO once daily (25 mg if East Asian ancestry or hepatic impairment). Titrate by 25–50 mg every 2 weeks (max 75 mg/day) to maintain platelets ≥50 × 10⁹/L. Take on empty stomach (1 h before or 2 h after food); separate from divalent cation-containing products (antacids, calcium, iron, dairy) by ≥4 hours.
Paediatric dose
≥1 year: Start 1 mg/kg/day PO (max 50 mg) for <6 years; 50 mg/day for ≥6 years. Titrate by 0.5 mg/kg every 2 weeks (max 75 mg/day). Must avoid food for 2 h before/after dose.
Efficacy
RAISE trial: 79% vs 28% (placebo) achieved sustained platelet response. PETIT-2 (paediatric): 62% achieved platelet ≥50 × 10⁹/L for ≥6 weeks.
Key risks
Hepatotoxicity (elevated transaminases in 10–13%; serious hepatic injury rare). Thromboembolism (3%). Cataracts (develop and progress). Requires monthly LFTs, ophthalmological monitoring every 6 months.
Renal adjustment
No dose adjustment. Monitor for iron/ferritin depletion.
Hepatic adjustment
Start 25 mg/day if total bilirubin >1.5 × ULN. Contraindicated if severe hepatic impairment. Monitor LFTs fortnightly initially, then monthly.
PBS status
🔑 Authority Required (Specialist) — Initial authority for 12 weeks. Continuing authority requires demonstrated response and absence of hepatic toxicity.
Rituximab
Rituximab
MabThera® · Anti-CD20 monoclonal antibody
Adult dose
375 mg/m² IV weekly × 4 weeks (lymphoma schedule) OR 100 mg IV weekly × 4 weeks (reduced dose — similar efficacy in ITP per GODEFRIDUS trial). Premedicate with paracetamol, antihistamine, and hydrocortisone 100 mg IV.
Paediatric dose
375 mg/m² IV × 4 weekly doses. Limited evidence; reserved for refractory ITP in children failing TPO-RAs. Off-label use.
Efficacy
Overall response ~60% (complete response ~40%). Median duration of response 1–2 years. Sustained response (≥5 years) in ~20–25%. Less effective in refractory ITP with platelets <15 × 10⁹/L.
Key risks
Infusion reactions (first dose), serum sickness (1–3%), prolonged hypogammaglobulinaemia, HBV reactivation (screen all patients), progressive multifocal leukoencephalopathy (PML — rare but fatal), late-onset neutropenia (5–15%).
Renal adjustment
No dose adjustment required
PBS status
🔑 Not PBS-listed for ITP — PBS-listed for RA, ANCA vasculitis, lymphoma, CLL. For ITP: privately funded or hospital special access. Cost ~ 500– 000 per course (reduced dose).
Fostamatinib and avatrombopag: Fostamatinib (Tavalisse®), a SYK inhibitor, and avatrombopag (Doptelet®), an oral TPO-RA, are FDA-approved for chronic ITP but are not currently TGA-registered or PBS-listed in Australia. They remain available only via Special Access Scheme (SAS) Category B for refractory cases.
Third-Line / Refractory ITP
Approximately 10–20% of ITP patients are refractory to first- and second-line therapies. Options include:
- Splenectomy: Laparoscopic splenectomy offers sustained complete response in 60–70%. Pre-operative vaccination essential: pneumococcal (Pneumovax 23® + Prevenar 13® at least 2 weeks prior, ideally 6 weeks), meningococcal (Nimenrix® — MenACWY), Haemophilus influenzae type b. Lifelong post-splenectomy antibiotic prophylaxis with phenoxymethylpenicillin 250 mg PO BD (or 500 mg daily) recommended by RACGP guidelines.
- Combination therapy: TPO-RA + rituximab may achieve higher and more durable responses than either agent alone (SYNERGY study ongoing).
- Mycophenolate mofetil: 1 g PO BD — emerging evidence as steroid-sparing agent; response rate ~40–60% in refractory ITP.
- Azathioprine: 2 mg/kg/day PO — slow onset (3–6 months); response rate ~40–50%. PBS General Benefit.
- Cyclosporin: 2–3 mg/kg/day PO — limited evidence; used in refractory cases. Monitor renal function and blood pressure.
- Danazol: 200 mg PO TDS — androgen; response in ~40–60%; hepatotoxicity monitoring required. Limited availability in Australia.
Emergency Management of Life-Threatening Bleeding
1
Immediate Measures
IVIg 1 g/kg (can infuse over 4 hours in emergency). Methylprednisolone 1 g IV daily × 1–3 days. Apply direct pressure to accessible bleeding sites. Hold anticoagulants and antiplatelets.
2
Platelet Transfusion
Transfuse platelets (1 adult dose apheresis or 4 pooled random donor units) — always concurrently with IVIg or tranexamic acid to prolong transfused platelet survival. Platelet increments are transient (hours) but can provide haemostasis during intervention.
3
Tranexamic Acid
1 g IV over 10 minutes (or 1 g PO TDS) — antifibrinolytic; stabilises clot at sites of mucosal bleeding. Avoid in haematuria (ureteric obstruction risk).
4
Specialist Referral & Escalation
Urgent haematology consultation. Consider emergency splenectomy if refractory. For ICH: neurosurgical consultation, CT head emergently, ICU admission.
Monitoring
| Agent | Monitoring | Frequency |
|---|---|---|
| Corticosteroids | Blood glucose, blood pressure, weight, bone density (if >3 months use) | Weekly during treatment; DEXA if prolonged |
| IVIg | Renal function, haemolysis markers (DAT, LDH, haptoglobin), fluid balance | Before each infusion; 24–48 h post if symptoms |
| Romiplostim | FBC with platelet count, peripheral blood film (reticulin), thromboembolic symptoms | Weekly during titration; monthly when stable; blood film every 6–12 months |
| Eltrombopag | LFTs, FBC, ophthalmological exam (cataracts), iron studies | LFTs fortnightly × 3 months then monthly; eye exam every 6 months |
| Rituximab | Immunoglobulin levels (IgG, IgA, IgM), HBV DNA, CD19 B-cell count | IgG at 3-monthly; HBV DNA if carrier; CD19 at 3–6 months post-treatment |
| Post-splenectomy | FBC (for target Howell–Jolly bodies), infection surveillance, vaccination status | FBC annually; lifelong fever monitoring (<38°C = immediate medical review) |
Special Populations
Pregnancy
Platelet threshold for treatment: <30 × 10⁹/L in first/second trimester; <50 × 10⁹/L in third trimester; <80 × 10⁹/L for epidural anaesthesia and <50 × 10⁹/L for caesarean section.
First-line: IVIg 1 g/kg is preferred (does not cross placenta at therapeutic doses). Prednisolone is second-line — prednisolone is largely inactivated by placental 11β-HSD2 (only ~10% reaches fetus) and is preferred over dexamethasone.
Avoid: Dexamethasone (crosses placenta — risk of fetal adrenal suppression). TPO-RAs are contraindicated (Category B3; romiplostim embryotoxic in animal studies). Rituximab is Category C — may cause fetal B-cell depletion; avoid if possible.
Neonatal: Maternal anti-platelet antibodies cross the placenta. 10–25% of neonates develop transient thrombocytopenia. Cord blood platelet count at delivery; if <50 × 10⁹/L, cranial ultrasound and neonatal IVIg.
Multidisciplinary team: obstetrician, haematologist, anaesthetist, neonatologist. RANZCOG guidelines apply.
Paediatrics
Watchful waiting: 75–80% of childhood ITP resolves spontaneously within 6–12 months. Observation alone is appropriate if platelets >20 × 10⁹/L and no significant bleeding.
When to treat: Platelets <10 × 10⁹/L, or <20 × 10⁹/L with mucosal bleeding, or preceding high-risk activities. First-line: prednisolone 1–2 mg/kg/day × 1–2 weeks or IVIg 0.8–1 g/kg.
Avoid aspirin and NSAIDs — increased bleeding risk. Paracetamol for analgesia.
Activity restriction: Recommend avoidance of contact sports (rugby, martial arts) while platelets <50 × 10⁹/L. Cycling with helmet is generally permitted if platelets >30 × 10⁹/L.
TPO-RAs: Eltrombopag (TGA-approved ≥1 year) and romiplostim (TGA-approved ≥1 year) for chronic ITP in children failing first-line therapy. PETIT-2 trial supported eltrombopag; IMPACT trial supported romiplostim.
Splenectomy: Generally deferred until age ≥5 years (overwhelming post-splenectomy infection risk). Presplenectomy vaccination as per ATAGI schedule.
Refer to Australian and New Zealand Children's Haematology/Oncology Group (ANZCHOG) guidelines. Avoid unnecessary testing — no bone marrow biopsy required for typical paediatric ITP.
Elderly (≥65 years)
Increased bleeding risk: Concurrent anticoagulants (warfarin, DOACs), antiplatelets (aspirin, clopidogrel), and falls risk substantially increase haemorrhage risk even at higher platelet counts.
Treatment threshold: Consider treating at platelet count <50 × 10⁹/L if on anticoagulation or dual antiplatelet therapy.
Steroid toxicity: Higher risk of steroid-induced diabetes, osteoporosis, proximal myopathy, psychiatric effects, and GI bleeding. Limit corticosteroid duration; early introduction of second-line agents (TPO-RAs) preferred.
Bone marrow: Mandatory bone marrow biopsy before ITP diagnosis in patients ≥60 years to exclude myelodysplastic syndrome (MDS), which commonly presents with isolated thrombocytopenia.
Splenectomy carries higher perioperative morbidity in elderly. TPO-RAs are increasingly preferred over splenectomy for second-line therapy in this population.
Renal Impairment
Exclude uraemic thrombocytopathy: Chronic kidney disease causes qualitative platelet dysfunction independent of count. Desmopressin (DDAVP) 0.3 mcg/kg IV over 30 min or cryoprecipitate may improve platelet function.
IVIg: Use glycine-stabilised preparations (Intragam P®). Avoid sucrose-stabilised IVIg in eGFR <30 — osmotic nephrosis risk. Monitor renal function post-infusion.
TPO-RAs: Romiplostim: no dose adjustment, no significant renal clearance. Eltrombopag: minimal renal excretion, no adjustment required.
Hepatitis C-associated ITP may coexist with HCV-related glomerulonephritis. Multidisciplinary nephrology/haematology input recommended.
Hepatic Impairment
Exclude portal hypertension: Cirrhosis causes thrombocytopenia via splenic sequestration (hypersplenism) and reduced TPO production by hepatocytes. Distinguish from concurrent ITP.
Eltrombopag: Start at 25 mg/day if bilirubin >1.5 × ULN. Avoid if Child–Pugh C. Monthly LFT monitoring essential. Note: eltrombopag is PBS-listed for thrombocytopenia in chronic liver disease (CLD) separate from ITP indication.
Rituximab: Risk of HBV reactivation — screen HBsAg and anti-HBc. If HBsAg positive, commence entecavir 0.5 mg PO daily prior to rituximab and continue for ≥12 months after last rituximab dose. If anti-HBc positive/HBsAg negative, monitor HBV DNA monthly during and for 12 months after rituximab.
HCV-associated ITP should be treated with antiviral therapy (direct-acting antivirals, PBS-listed) as first-line — this may resolve thrombocytopenia without immunosuppression.
Immunocompromised
HIV-associated ITP: Responds to antiretroviral therapy (ART) — platelets often improve within 4–8 weeks of ART initiation. IVIg and corticosteroids are effective for acute bleeding. Splenectomy is effective but avoided due to immunosuppression risk.
Rituximab in immunocompromised: Risk of prolonged hypogammaglobulinaemia and opportunistic infections. Pre-treatment: check quantitative immunoglobulins. If IgG <4 g/L, consider subcutaneous immunoglobulin (SCIG) supplementation before rituximab.
CLL-associated ITP: May respond to CLL-directed therapy (ibrutinib, venetoclax) in addition to ITP-specific treatment. Often refractory to standard ITP therapies.
SOT and post-HSCT ITP require specialist haematology management. Distinguish from post-transplant thrombotic microangiopathy (TMA).
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
Quick Reference: ITP Treatment Algorithm
Newly diagnosed ITP — platelets <30 × 10⁹/L or bleeding
Prednisolone 1 mg/kg/day × 1–2 wk then taper; OR dexamethasone 40 mg/day × 4 days
4–6 weeks (prednisolone) or 1–3 cycles (dexamethasone)
Add IVIg 1 g/kg if urgent platelet rise needed (<24 h)
Refractory / persistent ITP >3–6 months
Romiplostim 1 mcg/kg SC/week; OR eltrombopag 50 mg PO daily
Ongoing with monthly monitoring
PBS Authority Required. Taper after 6–12 months to test for sustained remission.
TPO-RA refractory or intolerant
Rituximab 375 mg/m² IV weekly × 4 (or 100 mg × 4 reduced dose)
4 doses over 4 weeks
Off-PBS for ITP. Screen HBV. Check IgG before treatment.
All medical therapy failed — chronic refractory
Laparoscopic splenectomy
One-off procedure; assess response at 3–6 months
Pre-vaccination mandatory. Lifelong penicillin prophylaxis. Sustained remission 60–70%.
Emergency life-threatening bleeding
IVIg 1 g/kg + methylprednisolone 1 g IV + platelet transfusion + tranexamic acid 1 g IV
Immediate, ongoing until haemostasis achieved
ICU admission. Neurosurgical consultation for ICH. Emergency haematology review.
📚 References
- 1. Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780–3817. doi:10.1182/bloodadvances.2019000812
- 2. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829–3866. doi:10.1182/bloodadvances.2019000966
- 3. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386–2393. doi:10.1182/blood-2008-07-162503
- 4. Mithoowani S, Gregory-Miller K, Goy J, et al. High-dose dexamethasone compared with standard-dose prednisone for initial treatment of primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol. 2016;3(10):e489–e496. doi:10.1016/S2352-3026(16)30103-3
- 5. Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011;377(9763):393–402. doi:10.1016/S0140-6736(10)60959-2
- 6. Tarantino MD, Bussel JB, Blanchette VS, et al. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016;388(10039):45–54. doi:10.1016/S0140-6736(16)00279-8
- 7. Arnold DM, Heddle NM, Cook RJ, et al. Reduced-dose rituximab in adults with immune thrombocytopenia: a randomised controlled trial (GODEFRIDUS). Blood. 2023;142(Supplement 1):67. doi:10.1182/blood-2023-181748
- 8. Frederiksen H, Maegbaek ML, Norgaard M. Twenty-year mortality of adult patients with primary immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol. 2014;166(2):260–267. doi:10.1111/bjh.12869
- 9. Grace RF, Despotovic JM, Bennett CM, et al. Eltrombopag in children with immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2018;391(10115):30–38. doi:10.1016/S0140-6736(17)32859-4
- 10. Australian Government Department of Health. National Blood Authority. National Guidelines for the Use of Immunoglobulin in Australia. 2023. Available at: www.blood.gov.au
- 11. RANZCOG (Royal Australian and New Zealand College of Obstetricians and Gynaecologists). Management of Thrombocytopenia in Pregnancy. College Statement C-Obs 67. 2022.
- 12. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander Health Performance Framework 2023. Canberra: AIHW; 2023.
- 13. Australasian Society for Clinical Immunology and Allergy (ASCIA), RACGP. Australian Immunisation Handbook: Post-Splenectomy Vaccination and Prophylaxis. Australian Government Department of Health; 2023.
- 14. Ghanima W, Godeau B, Cines DB, Bussel JB. How I treat immune thrombocytopenia: the choice between splenectomy or a medical therapy as a second-line treatment. Blood. 2012;120(5):960–969. doi:10.1182/blood-2011-12-309153