Key Facts

ITP is an acquired autoimmune disorder characterised by isolated low platelet count resulting from immune-mediated platelet destruction and impaired platelet production. It is a diagnosis of exclusion.

Epidemiology

• Adult incidence: 3-4 per 100,000/year in the UK
• Childhood ITP: typically post-viral, acute, self-limiting (80% resolve within 6 months)
• Adult ITP: more likely chronic (lasting >12 months)
• Female predominance in adults (F:M 2:1)
• Prevalence increases with age

Aetiology

• Primary ITP: idiopathic (no identifiable trigger)
• Secondary ITP: associated with SLE, antiphospholipid syndrome, CLL, HIV, hepatitis C, H. pylori, drugs (heparin excluded – separate entity)
• Post-viral ITP common in children (follows URTI)

Pathophysiology

• Autoantibodies (usually IgG) target platelet surface glycoproteins (GPIIb/IIIa, GPIb/IX)
• Antibody-coated platelets phagocytosed by splenic macrophages (Fc receptor-mediated)
• Reduced platelet production: autoantibodies also inhibit megakaryocyte function
• T-cell-mediated platelet destruction also contributes
• Relative thrombopoietin deficiency (inadequate compensatory production)

Mild Thrombocytopenia (50-100 × 10⁹/L)

• Often asymptomatic
• Mild bruising

Moderate (20-50 × 10⁹/L)

• Petechiae (non-blanching pinpoint lesions)
• Purpura and easy bruising
• Mucosal bleeding: epistaxis, gingival bleeding, menorrhagia

Severe (<20 × 10⁹/L)

• Spontaneous bleeding
• Haemorrhagic bullae in the mouth
• Haematuria, gastrointestinal bleeding
• Intracranial haemorrhage (rare, <1%, but potentially fatal)

Red Flags

• Platelets <10 × 10⁹/L → highest risk of life-threatening bleeding
• Wet purpura (oral haemorrhagic bullae) → predictor of severe bleeding
• Headache or neurological symptoms → intracranial haemorrhage until proven otherwise
• Splenomegaly → unusual in ITP, consider alternative diagnosis

Bedside

• Examination: petechiae, purpura, mucosal bleeding; no splenomegaly expected

Bloods

• FBC: isolated thrombocytopenia – other cell lines normal
• Blood film: large platelets, no fragments (rules out TTP), no blast cells
• Reticulocyte count: normal (helps exclude marrow failure)
• Coagulation screen: normal (PT, APTT) – differentiates from DIC
• LDH, haptoglobin, bilirubin: to exclude haemolysis/TTP
• HIV, Hepatitis B and C serology: exclude secondary causes
• H. pylori testing: treat if positive (may improve platelet count)
• ANA, antiphospholipid antibodies: if SLE suspected
• Immunoglobulins: exclude CVID or CLL
• Thyroid function: associated autoimmune thyroid disease

Imaging

• Not routinely required
• CT if lymphoproliferative disorder suspected

Special Tests

• Bone marrow biopsy: not routinely required in typical ITP; indicated if age >60 (exclude MDS), atypical features, or pre-splenectomy
• Antiplatelet antibodies: poor sensitivity and specificity – NOT recommended routinely

Non-pharmacological

• Avoid contact sports and activities with high bleeding risk
• Avoid antiplatelet agents and anticoagulants
• No treatment if platelets >30 × 10⁹/L and asymptomatic (watch and wait)

Pharmacological

First-line (platelets <30 or significant bleeding):

• Prednisolone 1mg/kg/day PO for 2 weeks, then taper over 4-8 weeks; OR
• Dexamethasone 40mg OD for 4 days (may be repeated q14-28 days × 1-4 cycles)
• Response rate: 60-80%, but relapse common on taper

Emergency (life-threatening bleeding or <10 with wet purpura):

• IV immunoglobulin (IVIg) 1g/kg (single dose or 2 consecutive days) – rapid rise within 24-48h
• Platelet transfusion: only in life-threatening haemorrhage (short-lived effect)
• Tranexamic acid 1g TDS PO/IV – adjunct for mucosal bleeding
• Methylprednisolone 1g IV for 3 days

Second-line (relapsed/refractory):

• Eltrombopag 50mg OD (TPO receptor agonist, oral)
• Romiplostim 1-10mcg/kg SC weekly (TPO receptor agonist)
• Rituximab 375mg/m² IV weekly × 4 (response rate ~60%, durable in ~30%)
• Splenectomy: considered after 12 months if refractory; cure rate ~60-70%
• Fostamatinib 100-150mg BD (SYK inhibitor)

Referral Criteria

• All new cases of confirmed ITP → haematology
• Life-threatening bleeding → emergency haematology and critical care

• Childhood ITP: 80% resolve spontaneously within 6 months
• Adult ITP: chronic course in ~60-70%
• Mortality from bleeding: <1-2% overall (intracranial haemorrhage is main concern)
• Splenectomy achieves long-term remission in 60-70%
• TPO receptor agonists maintain response in 70-80% while on treatment
• Spontaneous remission can occur even years after diagnosis

ASH Guidelines Treatment Algorithm

Key Drug Summary