📋 Key Information Summary
- ITP, TTP, HELLP, and DIC all cause thrombocytopenia but arise from fundamentally different pathophysiological mechanisms — immune-mediated destruction (ITP), thrombotic microangiopathy (TTP), placental-mediated endothelial injury (HELLP), and consumptive coagulopathy (DIC).
- Rapid differentiation is critical: TTP carries >90% mortality without urgent plasma exchange; ITP is rarely life-threatening acutely.
- Schistocytes on blood film are present in TTP, HELLP, and DIC but are absent in ITP — this is the single most important bedside differentiator.
- ADAMTS13 activity <10% confirms TTP and mandates emergency plasma exchange; coagulation studies (PT/INR, aPTT, fibrinogen) are typically normal in ITP and TTP but deranged in DIC.
- HELLP is a pregnancy-specific syndrome (typically >20 weeks' gestation) characterised by haemolysis, elevated liver enzymes, and low platelets — delivery is the definitive treatment.
- DIC is always secondary — identify and treat the underlying cause (sepsis, trauma, obstetric catastrophe, malignancy) while supporting coagulation.
- ITP diagnosis is one of exclusion: isolated thrombocytopenia with normal coagulation, no schistocytes, and no alternative explanation.
- TTP requires urgent plasma exchange (PLEX) initiated within 4–6 hours of clinical suspicion — do not wait for ADAMTS13 results.
- In obstetric thrombocytopenia, gestational thrombocytopenia (most common, 75%) must be distinguished from pre-eclampsia/HELLP, TTP, and ITP.
- DIC management centres on treating the precipitant; platelet transfusion threshold is <10 × 10⁹/L (or <50 × 10⁹/L with active bleeding).
- Aboriginal and Torres Strait Islander women experience higher rates of pre-eclampsia and HELLP syndrome — lower thresholds for specialist review are recommended.
- The PLASMIC score can risk-stratify for TTP at the bedside while awaiting ADAMTS13 results.
Introduction & Australian Epidemiology
Thrombocytopenic syndromes — immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP), haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and disseminated intravascular coagulation (DIC) — share the common feature of a reduced platelet count but diverge profoundly in pathophysiology, clinical urgency, and management. Misidentification delays life-saving therapy, particularly plasma exchange for TTP or delivery for HELLP.
In Australia, ITP affects approximately 3–4 per 100,000 adults annually, with a bimodal distribution in young adults and the elderly. TTP incidence is approximately 3–5 per million per year; acquired TTP due to anti-ADAMTS13 autoantibodies predominates in adults, while Upshaw–Schulman syndrome (congenital) accounts for <5% of cases. HELLP complicates 0.5–0.9% of all pregnancies and 10–20% of severe pre-eclampsia presentations. DIC is not a primary diagnosis but a complication of severe sepsis (the most common cause in Australian ICUs), major trauma, obstetric emergencies (placental abruption, amniotic fluid embolism), and advanced malignancy.
This guideline provides a structured comparison to enable rapid differentiation and evidence-based management in Australian emergency, obstetric, and haematology settings.
Pathophysiology Comparison
Understanding the distinct mechanism of thrombocytopenia in each syndrome is essential for rational investigation and treatment.
| Feature | ITP | TTP | HELLP | DIC |
|---|---|---|---|---|
| Primary mechanism | Autoimmune IgG anti-platelet antibodies (GPIIb/IIIa, GPIb/IX) → Fc-mediated splenic destruction | Severe ADAMTS13 deficiency → uncleaved ultra-large vWF multimers → platelet-rich microthrombi | Placental endothelial injury → microangiopathic haemolysis + hepatic sinusoidal fibrin deposition | Widespread activation of coagulation → consumption of platelets, fibrinogen, clotting factors → microthrombi + haemorrhage |
| Coagulation cascade | Normal (PT, aPTT, fibrinogen) | Normal (PT, aPTT, fibrinogen) | Usually normal or mildly deranged | Markedly deranged — ↑PT/INR, ↑aPTT, ↓fibrinogen, ↑D-dimer |
| Schistocytes | Absent | Present (hallmark) | Present | Present |
| Haptoglobin | Normal | Low (consumed) | Low | Low |
| Fibrin deposition | No | Platelet-vWF microthrombi (no fibrin) | Hepatic sinusoidal fibrin | Widespread fibrin microthrombi |
| Key driver | Immune dysregulation | ADAMTS13 deficiency (autoimmune or congenital) | Placental pathology / pre-eclampsia spectrum | Systemic inflammatory response (tissue factor release) |
Critical distinction: ITP and TTP have normal coagulation studies. DIC is defined by abnormal coagulation. This single set of bloods (PT/INR, aPTT, fibrinogen) rapidly narrows the differential.
Clinical Context — Obstetric, Sepsis, and Autoimmune Settings
Obstetric Thrombocytopenia
Thrombocytopenia occurs in approximately 7–10% of pregnancies. The differential narrows by gestational age:
Most Common
Gestational Thrombocytopenia
Mild (70–150 × 10⁹/L), third trimester, no maternal or neonatal consequences. Platelets recover post-partum. No treatment required.
Setting: Outpatient obstetric care
Moderate Concern
Pre-eclampsia / HELLP
Usually >20 weeks. Hypertension, proteinuria, RUQ pain, elevated LDH, elevated AST/ALT. Schistocytes present. Delivery is definitive treatment.
Setting: Tertiary obstetric unit with neonatal ICU access
Life-Threatening
TTP or AFLP in Pregnancy
TTP peak incidence 2nd–3rd trimester. Pentad (thrombocytopenia, MAHA, renal impairment, fever, neurological symptoms) often incomplete. Plasma exchange must not be delayed.
Setting: ICU + haematology + obstetric MDT
Sepsis-Associated DIC
DIC complicates 25–50% of sepsis admissions to Australian ICUs. Gram-negative bacteraemia (especially Escherichia coli, Neisseria meningitidis) and Staphylococcus aureus are common triggers. The ISTH DIC score (platelets, fibrinogen, D-dimer, PT prolongation) provides a rapid diagnostic framework.
Do not treat DIC in isolation. DIC is always secondary. Source control and empirical antibiotics (within 1 hour for septic shock) must precede or accompany blood product support.
Autoimmune / ITP Context
Primary ITP is a diagnosis of exclusion. Secondary ITP may occur in association with SLE, antiphospholipid syndrome (APS), CLL, H. pylori infection, hepatitis C, HIV, or post-vaccination. In APS, thrombocytopenia may paradoxically coexist with thrombosis — this mimics DIC but coagulation studies are normal. Drug-induced thrombocytopenia (heparin, quinine, valproate, vancomycin) must always be excluded.
Thrombotic Microangiopathy (TMA) Overlap
TTP, STEC-HUS, complement-mediated HUS, and HELLP all fall under the TMA umbrella. ADAMTS13 testing distinguishes TTP (ADAMTS13 <10%) from other TMAs. In pregnancy, the distinction between HELLP and TTP is critical because treatment differs fundamentally — delivery for HELLP versus plasma exchange for TTP.
Key Investigations to Differentiate
The following investigations, arranged by urgency, should be performed in all patients presenting with thrombocytopenia of uncertain aetiology.
Essential
Full Blood Count + Blood Film
Schistocytes (present in TTP, HELLP, DIC; absent in ITP). Assess platelet count trajectory (acute drop vs chronic). MBS item 65070.
Essential
Coagulation — PT/INR, aPTT, Fibrinogen, D-dimer
Normal in ITP and TTP. Prolonged PT/INR, prolonged aPTT, low fibrinogen, and markedly elevated D-dimer in DIC. MBS item 65120.
Essential
LDH, Haptoglobin, Indirect Bilirubin, Reticulocyte Count
Elevated LDH + low haptoglobin + elevated indirect bilirubin = haemolysis (present in TTP, HELLP, DIC; absent in ITP). MBS item 66500/66512.
Essential
Liver Function Tests (AST, ALT)
Markedly elevated in HELLP (≥2× ULN). Mildly elevated or normal in ITP, TTP, DIC unless hepatic involvement. MBS item 66510.
Essential
Creatinine, Urea, Electrolytes, Urinalysis
Renal impairment in TTP, HELLP, and DIC. Normal in isolated ITP. MBS item 66509.
Specialist
ADAMTS13 Activity + Inhibitor
Gold standard for TTP diagnosis. Activity <10% = TTP. Results typically 24–72 hours. Do not delay plasma exchange while awaiting result. Sent to reference laboratory (e.g., RCPA-accredited labs). MBS item 66826.
Available
PLASMIC Score (bedside)
Validated tool to risk-stratify for severe ADAMTS13 deficiency while awaiting results. Score ≥6 = high risk (positive predictive value ~90%). Parameters: platelet count, haemolysis, INR, MCV, active cancer, history of stem-cell transplant, creatinine.
Available
Peripheral Blood Flow Cytometry
Useful if CLL or lymphoproliferative disorder suspected as cause of secondary ITP.
Available
Anti-platelet Antibody Assays
Not routinely recommended for ITP diagnosis (poor sensitivity/sensitivity). Consider in refractory cases.
Specialist
Complement Studies (C3, C4, Factor H, Factor I)
Consider if complement-mediated HUS suspected (ADAMTS13 normal, no schistocytes but TMA features persist).
PLASMIC Score reference: Platelet count <30 (1 pt), haemolysis present (1 pt), INR <1.5 (1 pt), MCV <90 fL (1 pt), no active cancer (1 pt), no stem-cell/organ transplant (1 pt), creatinine <2 mg/dL (1 pt). Score ≥6: high risk for severe ADAMTS13 deficiency — proceed directly to plasma exchange.
Investigation Comparison Table
| Test | ITP | TTP | HELLP | DIC |
|---|---|---|---|---|
| Platelet count | ↓ (often <100) | ↓↓ (often <30) | ↓ (<100) | ↓ (variable) |
| Schistocytes | Absent | Present | Present | Present |
| PT/INR | Normal | Normal | Normal/mild ↑ | Prolonged |
| aPTT | Normal | Normal | Normal | Prolonged |
| Fibrinogen | Normal | Normal | Normal/elevated | Low |
| D-dimer | Normal | Mildly ↑ | ↑ | ↑↑↑ |
| LDH | Normal | ↑↑ | ↑↑ | ↑ |
| Haptoglobin | Normal | Low | Low | Low |
| AST/ALT | Normal | Normal/mild ↑ | ↑↑ (≥2× ULN) | Variable |
| ADAMTS13 | Normal | <10% | Normal/mild ↓ | Variable |
| Creatinine | Normal | Often ↑ | Often ↑ | Often ↑ |
Management Differences
Emergency Priorities by Syndrome
ITP
Treat if bleeding or platelets <20–30 × 10⁹/L
Not an emergency unless life-threatening haemorrhage. First-line: corticosteroids (prednisolone 1 mg/kg PO daily). Second-line: IV immunoglobulin (IVIg) for rapid rise. Platelet transfusion only for life-threatening bleed.
TTP
EMERGENCY — plasma exchange within 4–6 hours
Do not await ADAMTS13 confirmation. Daily plasma exchange until platelets >150 × 10⁹/L for ≥2 days. Add caplacizumab (if available) for faster platelet normalisation. Rituximab for refractory/relapsing cases. Platelet transfusion is contraindicated unless life-threatening haemorrhage.
HELLP
Definitive treatment = delivery
Corticosteroids (dexamethasone) to promote fetal lung maturity if <34 weeks. Magnesium sulphate for seizure prophylaxis. Antihypertensives (labetalol, nifedipine, hydralazine). Platelet transfusion if <50 × 10⁹/L and delivery/C-section anticipated.
DIC
Treat the underlying cause + supportive care
Source control (drainage, debridement). Empirical antibiotics for sepsis. Cryoprecipitate if fibrinogen <1.0 g/L. Platelet transfusion if <10 × 10⁹/L (or <50 × 10⁹/L with bleeding). FFP if prolonged PT/INR with active bleeding. Heparin in specific contexts (e.g., acute promyelocytic leukaemia).
Pharmacotherapy Comparison
Prednisolone
Solone® · Panafcortelone® · Corticosteroid
Adult dose
ITP: 1 mg/kg PO daily (max 80 mg), taper after 2–3 weeks. HELLP: dexamethasone 10 mg IV 12-hourly preferred.
Paediatric dose
ITP: 2–4 mg/kg/day PO (max 60 mg), taper over 2–3 weeks.
Indication
First-line ITP. Adjunctive in HELLP (dexamethasone).
PBS status
✔ PBS General Benefit
IV Immunoglobulin (IVIg)
Intragam® P / Privigen® · Immunomodulator
Adult dose
ITP: 1 g/kg IV over 1–2 days. TTP: 0.4 g/kg/day IV for 5 days (if PLEX unavailable).
Paediatric dose
ITP: 0.8–1 g/kg IV over 1–2 days.
Indication
Second-line ITP (rapid platelet rise needed). Bridging for TTP if PLEX delayed. Neonatal alloimmune thrombocytopenia.
PBS status
⚠ PBS Authority Required
Caplacizumab
Cablivi® · Anti-vWF nanobody
Adult dose
11 mg IV (first dose, pre-PLEX), then 11 mg SC daily until 30 days after PLEX cessation.
Indication
Acquired TTP — adjunct to plasma exchange and immunosuppression. Reduces time to platelet normalisation and recurrence.
PBS status
✘ Not PBS listed
Rituximab
Mabthera® / Riximyo® · Anti-CD20 monoclonal antibody
Adult dose
375 mg/m² IV weekly × 4 weeks (TTP or refractory ITP).
Indication
Refractory/relapsing TTP (added to PLEX). Refractory ITP (second/third-line). Reduces relapse risk in TTP.
PBS status
⚠ PBS Authority Required (indication-dependent)
Cryoprecipitate
Blood product · Fibrinogen replacement
Adult dose
10 units (pooled) IV; target fibrinogen >1.5 g/L in DIC, >1.0 g/L in obstetric haemorrhage.
Indication
DIC with hypofibrinogenemia (<1.0 g/L). Massive obstetric haemorrhage. Not indicated in ITP or TTP.
PBS status
✔ Blood product (no PBS charge)
Platelet Transfusion Thresholds
Contraindication alert: Platelet transfusion in TTP may worsen thrombosis and is contraindicated except in life-threatening haemorrhage or immediately prior to urgent surgery. This is a critical patient-safety distinction from ITP, HELLP, and DIC.
| Syndrome | Transfusion Threshold | Rationale |
|---|---|---|
| ITP | Only for life-threatening haemorrhage (any count) | Rapid immune-mediated destruction; platelets may be consumed in <1 hour. Use IVIg to extend survival. |
| TTP | Contraindicated unless life-threatening bleeding or urgent surgery | May fuel microvascular thrombosis and worsen organ damage. |
| HELLP | <50 × 10⁹/L if delivery/C-section planned | Procedural safety for neuraxial anaesthesia and surgery. |
| DIC | <10 × 10⁹/L prophylactic; <50 × 10⁹/L with active bleeding | Consumptive loss; transfusion is supportive alongside cause-directed therapy. |
Special Populations
Pregnancy
Gestational thrombocytopenia — most common cause (75%); observe only.
HELLP — delivery is definitive; corticosteroids if <34 weeks; magnesium sulphate; monitor for subcapsular hepatic haematoma.
TTP in pregnancy — plasma exchange same as non-pregnant; caplacizumab safety in pregnancy not established; rituximab avoid if possible.
ITP in pregnancy — prednisolone or IVIg safe; target platelets >30 × 10⁹/L antenatally, >50 × 10⁹/L for delivery. Neonatal platelet count should be checked at birth.
Neuraxial anaesthesia generally safe if platelets >80 × 10⁹/L; discuss with anaesthetist.
Paediatrics
Childhood ITP — 80% resolve spontaneously within 6 months. Observe if no bleeding and platelets >20 × 10⁹/L. IVIg or corticosteroids if mucosal bleeding or pre-procedure.
Paediatric TTP — consider congenital (Upshaw–Schulman syndrome) if onset <18 years; ADAMTS13 gene mutation testing; regular fresh frozen plasma infusions.
STEC-HUS — important paediatric TMA mimic; bloody diarrhoea prodrome, ADAMTS13 normal. Supportive care; avoid antibiotics in confirmed STEC. Contact public health.
Platelet transfusion threshold in paediatric DIC: <10 × 10⁹/L or <50 × 10⁹/L with bleeding.
Elderly
ITP in elderly — secondary causes more common (CLL, myelodysplasia, H. pylori). Treatment threshold may be higher (30–40 × 10⁹/L) due to fall risk and anticoagulant use.
TTP in elderly — acquired TTP median age ~40 but can present at any age. Higher mortality in elderly due to comorbidities.
DIC in elderly — sepsis is the most common trigger; frailty assessment and goals-of-care discussion essential before invasive interventions.
Renal Impairment
TTP — renal impairment common; plasma exchange dose adjustments not required. Monitor potassium in cryoprecipitate-poor plasma use.
HELLP — acute kidney injury may complicate; monitor urine output and creatinine daily.
ITP — eltrombopag (TPO agonist) dose adjustment for hepatic, not renal. Avoid NSAIDs for bleeding risk.
Hepatic Impairment
Chronic liver disease — thrombocytopenia due to portal hypertension + splenic sequestration (distinct from ITP). TPO agonists (avatrombopag, lusutrombopag) available for pre-procedural use — PBS listed for chronic liver disease.
HELLP — hepatic rupture (subcapsular haematoma) is a rare but life-threatening complication; CT abdomen if persistent RUQ pain post-delivery.
Immunocompromised
HIV-associated ITP — treat with ART first; antiretroviral response alone may resolve thrombocytopenia. IVIg and corticosteroids are effective short-term.
SLE-related ITP — may overlap with APS (thrombotic risk); assess lupus anticoagulant and anticardiolipin antibodies. Hydroxychloroquine + corticosteroids.
Post-transplant TMA — calcineurin inhibitor toxicity; distinct from TTP; ADAMTS13 usually normal. Reduce immunosuppression; eculizumab if complement-mediated.
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
Aboriginal and Torres Strait Islander Australians experience disproportionate burden from conditions that cause thrombocytopenic syndromes, particularly hypertensive disorders of pregnancy and sepsis.
📚 References
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