Immune Thrombocytopenia (ITP)

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder in which antibodies directed against platelet surface glycoproteins cause both accelerated platelet destruction and, in many patients, an inappropriately blunted marrow production response. It is a diagnosis of exclusion: isolated thrombocytopenia (platelet count under 100 ×10⁹/L) in an otherwise well patient, with no other explanation identified. ITP is classified as primary (no underlying cause) or secondary (associated with another condition — systemic lupus erythematosus, chronic lymphocytic leukemia, HIV, hepatitis C, H. pylori infection, common variable immunodeficiency, or certain drugs), and by phase from diagnosis: newly diagnosed (0-3 months), persistent (3-12 months), and chronic (over 12 months).^[1] The single most important management principle is that bleeding risk does not track tightly with the platelet count — a stable patient with a very low count and only minor bruising may need no pharmacologic treatment at all, while treatment decisions are driven by the platelet count together with the pattern and severity of bleeding.

Presentation ranges from an incidental low platelet count on routine bloodwork to overt mucocutaneous bleeding. "Wet" purpura — mucosal bleeding such as oral blood blisters, gum bleeding, or epistaxis — signals a materially higher near-term bleeding risk than "dry" purpura confined to the skin (petechiae, ecchymoses), and this distinction matters more for urgency than the platelet count alone.

• Petechiae (pinpoint, non-blanching) and ecchymoses (bruising), often out of proportion to any trauma.
• Epistaxis, gingival bleeding, and menorrhagia.
• Oral mucosal blood blisters (wet purpura) — an important bleeding-risk marker.
• Fatigue is common but nonspecific.
• Splenomegaly and lymphadenopathy are not typical of primary ITP — their presence should prompt a search for a secondary cause instead.

• Recent viral infection, particularly in children — often precedes an acute, self-limited episode.
• Underlying autoimmune disease — systemic lupus erythematosus, autoimmune thyroid disease, antiphospholipid syndrome.
• Lymphoproliferative disorders — chronic lymphocytic leukemia, lymphoma.
• Chronic infection — HIV, hepatitis C, and H. pylori (eradication can improve the platelet count in infected patients with ITP).
• Common variable immunodeficiency.
• Certain drugs associated with immune-mediated thrombocytopenia (a distinct entity from primary ITP) — quinine, vancomycin, sulfonamides, and some anticonvulsants.
• Pregnancy — ITP can first present or worsen during pregnancy; gestational thrombocytopenia is a distinct, more common, and generally benign cause of mild thrombocytopenia in pregnancy that must be distinguished from it.
• Recent vaccination — rare, usually mild and self-limited.

Differentiating the causes of new thrombocytopenia

History

• Bleeding history — site, severity, and whether it is new or longstanding.
• Full medication review, looking specifically for a new drug that could cause immune-mediated thrombocytopenia.
• Recent infection, autoimmune symptoms, family history of thrombocytopenia, pregnancy status, recent vaccination, and alcohol intake.

Examination

Characterize the bleeding pattern (dry versus wet purpura). Splenomegaly or lymphadenopathy is atypical for primary ITP and should prompt evaluation for a secondary cause instead.

Laboratory evaluation

• CBC with differential and a peripheral blood smear are mandatory — this both confirms isolated thrombocytopenia (other cell lines normal) and excludes pseudothrombocytopenia (repeat the count in a citrate tube if platelet clumping is seen) and other causes such as TTP (schistocytes) or leukemia (blasts).
• ITP is a diagnosis of exclusion — no single test confirms it. Platelet antibody testing is not recommended given poor sensitivity and specificity.^[2]
• Test for HIV, hepatitis C, and H. pylori — treating an identified infection can resolve secondary ITP.^[1]
• Direct antiglobulin (Coombs) test if hemolysis is suspected (Evans syndrome — combined ITP and autoimmune hemolytic anemia).
• Quantitative immunoglobulins, particularly in children, if common variable immunodeficiency is a consideration.
• ANA if lupus is clinically suspected.
• Bone marrow examination is not routinely required — reserve it for atypical features: involvement of other cell lines, abnormal cells on the smear, poor response to treatment, or an older patient being considered for splenectomy.^[2]

• Achieve a hemostatically safe platelet count — generally over 20-30 ×10⁹/L, or higher before a procedure — rather than a normal count.
• Stop active bleeding.
• Avoid unnecessary treatment of asymptomatic patients with a safe platelet count.
• Minimize treatment-related toxicity, particularly from prolonged corticosteroid use.
• Where possible, achieve durable remission off treatment with second-line therapy rather than indefinite maintenance.

• Avoid antiplatelet agents, NSAIDs, and anticoagulants unless clearly necessary and the bleeding risk has been specifically weighed.
• Avoid contact sports and other high bleeding-risk activities while significantly thrombocytopenic.
• Complete pneumococcal, meningococcal, and H. influenzae type b vaccination at least 2 weeks before an elective splenectomy.
• Patient education on bleeding precautions and when to seek urgent care (wet purpura, severe headache, or heavy bleeding of any kind).
• Treat an identified underlying cause (e.g., H. pylori eradication, stopping a causative drug) alongside — or sometimes instead of — ITP-specific pharmacotherapy.

Pregnancy

Breastfeeding

Corticosteroids and IVIG are compatible with breastfeeding. Data for TPO receptor agonists and rituximab are limited — specialist-directed decision.

Pediatrics

Most childhood ITP is self-limited, often following a viral illness, and resolves within 12 months without treatment. Favor observation over pharmacologic treatment even at low platelet counts if bleeding is minimal. When treatment is needed, a short corticosteroid course or IVIG is first-line. Avoid splenectomy under age 5 given infection risk, and defer it where possible until the chronic phase is clearly established. Romiplostim and eltrombopag are approved for refractory pediatric ITP down to 1 year of age.

Older adults

Bleeding risk at a given platelet count is higher than in younger patients, and corticosteroid toxicity (osteoporosis, hyperglycemia, psychiatric effects) is more consequential — favor shorter courses and earlier transition to a steroid-sparing second-line agent.

Hepatic impairment

Eltrombopag requires dose reduction in hepatic impairment (start at 12.5 mg/day) given hepatotoxicity risk and altered metabolism — monitor LFTs closely.

Check platelet count frequently (often weekly) during active treatment, spacing out once stable. Use a structured assessment of bleeding symptoms at every visit, not the platelet count in isolation. Monitor corticosteroid-related toxicity — glucose, bone density with prolonged or repeated courses, mood/sleep effects. Check LFTs regularly with eltrombopag or fostamatinib. Screen for thrombosis-related symptoms with any TPO receptor agonist. Confirm vaccination status well before any planned splenectomy. Reassess for a secondary cause if the clinical course is atypical or the response to standard therapy is unexpectedly poor.

1. Confirm the diagnosis is still correct — repeat the smear, exclude pseudothrombocytopenia, and reconsider TTP or a secondary cause if not already excluded.
2. Confirm adherence to the corticosteroid regimen and appropriate dose/duration before labeling it a steroid failure.
3. For relapse after a steroid taper, or steroid-dependence: move to a TPO receptor agonist, rituximab, or fostamatinib rather than repeating or prolonging corticosteroids.
4. For failure of one second-line agent: switch class (for example, a TPO receptor agonist to rituximab, or vice versa) rather than assuming every second-line option will fail.
5. For multi-refractory ITP: refer for splenectomy evaluation or combination therapy under specialist direction, and reconsider a secondary-ITP workup (bone marrow examination, expanded serologies) if not already done.
6. For emergency bleeding unresponsive to IVIG and corticosteroids: give a platelet transfusion (effective despite ongoing destruction), consider an antifibrinolytic (tranexamic acid), and obtain urgent hematology consultation.

• Treating an asymptomatic adult with a platelet count of at least 30 ×10⁹/L with corticosteroids instead of observing.
• Continuing corticosteroids beyond about 6 weeks as maintenance therapy instead of tapering and moving to a steroid-sparing second-line agent.
• Giving anti-D to an Rh-negative or previously splenectomized patient.
• Missing a hepatitis B screen before starting rituximab.
• Not counselling on the empty-stomach and mineral-separation requirement for eltrombopag, leading to reduced absorption and apparent treatment failure.
• Basing the decision to treat on the platelet count alone without considering actual bleeding symptoms and disease phase.
• Missing a drug cause of thrombocytopenia (for example, vancomycin or quinine) and treating it as primary ITP instead of stopping the causative agent.
• Confusing ITP with heparin-induced thrombocytopenia in a patient with recent heparin exposure — a different mechanism requiring different treatment.
• Missing TTP (schistocytes, neurologic or renal findings) and managing it as ITP — a delay in plasma exchange is life-threatening.

How to use this table: doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.

Corticosteroids

First-line for symptomatic ITP or a platelet count under 30 ×10⁹/L; use a short course, not chronic maintenance.

Immune globulin products

Reserved for emergency bleeding or when a rapid platelet rise is needed (for example, before an urgent procedure or in pregnancy).

Thrombopoietin receptor agonists (TPO-RAs)

Preferred 2nd-line option for relapsed, steroid-dependent, or steroid-refractory disease.

B-cell-depleting and other second-line immunomodulating agents

Alternatives to a TPO-RA, or used sequentially after TPO-RA failure.

Spleen tyrosine kinase (SYK) inhibitor

A later-line oral option after other second-line therapies.

Evidence note: drug inventory, dosing, adverse effects, and comments reflect standard Canadian practice, cross-checked against current ASH guidance.^[1]