What is the recommended diagnostic workup and management for immune thrombocytopenia (idiopathic thrombocytopenic purpura)?

Immune Thrombocytopenia (ITP): Diagnostic Workup and Management

Diagnosis

ITP is diagnosed by confirming isolated thrombocytopenia (platelet count <100 × 10⁹/L) on peripheral blood smear reviewed by a hematopathologist, together with mandatory HIV and hepatitis C testing in all adults, while bone marrow examination is unnecessary in patients with typical features. 1, 2

Essential Diagnostic Steps

Confirm true thrombocytopenia by repeating the platelet count in a citrate or heparin tube if pseudothrombocytopenia is suspected, as EDTA-dependent platelet clumping occurs in approximately 0.1% of samples and falsely lowers automated counts. 2

Obtain a complete blood count with differential to verify isolated thrombocytopenia; any unexplained anemia or leukopenia excludes primary ITP and mandates bone marrow evaluation. 1, 2

Peripheral blood smear review by a hematopathologist is mandatory because automated counters miss critical findings. 2 Expected findings in ITP include:

• Platelets of normal size or only mildly enlarged (giant platelets suggest inherited thrombocytopenias like MYH9-related disease or Bernard-Soulier syndrome) 2
• Normal red cell morphology without schistocytes (schistocytes indicate thrombotic microangiopathy with >90% mortality if untreated) 2
• Normal white cell morphology without immature cells, blasts, or inclusion bodies (abnormalities suggest leukemia or myelodysplastic syndrome) 2

Mandatory Testing to Exclude Secondary Causes

All adults must be tested for:

• HIV antibody – HIV-associated thrombocytopenia is clinically indistinguishable from primary ITP and may precede other HIV manifestations by years 1, 2
• Hepatitis C virus serology – chronic HCV can cause thrombocytopenia that resolves after successful antiviral therapy 1, 2
• Helicobacter pylori (urea-breath test or stool antigen, not serology) – eradication therapy normalizes platelet counts in a subset of adult ITP patients, especially in endemic regions 2

Additional context-specific testing:

• Pregnancy test in individuals of childbearing potential to differentiate gestational thrombocytopenia, pre-eclampsia, or HELLP syndrome 2
• Quantitative immunoglobulin levels to identify common variable immune deficiency, which can present initially as ITP 2
• Direct antiglobulin test (DAT) to exclude Evans syndrome (combined autoimmune hemolytic anemia and ITP) 2

Physical Examination Red Flags

The examination should be normal except for bleeding manifestations (petechiae, purpura, mucosal bleeding). 1, 2 The presence of any splenomegaly, hepatomegaly, or lymphadenopathy excludes primary ITP and mandates investigation for HIV, systemic lupus erythematosus, lymphoproliferative disorders, or chronic liver disease. 1, 2

When Bone Marrow Examination IS Required

Bone marrow aspiration and core biopsy with flow cytometry and cytogenetic studies are mandatory when any of the following are present: 1, 2

• Age ≥60 years (to exclude myelodysplastic syndrome, leukemia, or other malignancies)
• Systemic symptoms (fever, unexplained weight loss, night sweats, bone pain)
• Abnormal CBC parameters beyond isolated thrombocytopenia (unexplained anemia, leukopenia, or leukocytosis)
• Atypical peripheral smear findings (schistocytes, immature cells, giant platelets, leukocyte inclusion bodies)
• Organomegaly or lymphadenopathy on physical examination
• Minimal or no response to first-line ITP therapies (IVIg, corticosteroids, anti-D)
• Prior to splenectomy in chronic or persistent ITP

Bone marrow examination is NOT necessary in children and adolescents with typical ITP features, in children who fail IVIg therapy, or before initiating corticosteroids. 1

Tests That Should NOT Be Ordered

Do not routinely order: platelet-associated IgG, glycoprotein-specific antiplatelet antibodies, thrombopoietin levels, reticulated platelet counts, bleeding time, antiphospholipid antibodies (unless antiphospholipid syndrome is clinically suspected), or antinuclear antibodies (unless systemic lupus erythematosus is suspected). 2 These assays lack diagnostic specificity or proven clinical utility in ITP.

---

Management

Pediatric ITP: Initial Management

Children with no bleeding or mild bleeding (skin manifestations only such as bruising and petechiae) should be managed with observation alone regardless of platelet count. 1, 2 This is the most critical management principle because:

• Severe bleeding occurs in only 3% of children with ITP 2
• Intracranial hemorrhage risk is approximately 0.1-0.5%, with most occurring within the first 5 weeks of diagnosis 2
• The majority of children experience spontaneous remission within 6 months; approximately two-thirds recover without any therapeutic intervention 2

Treatment should be initiated only if clinically significant bleeding is present (moderate bleeding such as persistent epistaxis requiring intervention, oral bleeding, gastrointestinal bleeding, or blood in urine), not based on platelet number alone. 1, 2

Pediatric ITP: First-Line Pharmacologic Treatment

For pediatric patients requiring treatment, choose one of the following: 1

• Single dose of IVIg (0.8-1 g/kg) – preferred when rapid platelet increase is needed; side effects include headache and fever 1
• Short course of corticosteroids – avoid prolonged therapy due to significant toxicities including growth suppression, immunosuppression, and metabolic effects 1, 2
• Single dose of anti-D immunoglobulin (50-75 μg/kg) – only in Rh-positive, nonsplenectomized children; contraindicated in children with decreased hemoglobin due to bleeding or evidence of autoimmune hemolysis 1

Pediatric ITP: Second-Line Treatment

For children or adolescents with significant ongoing bleeding despite first-line treatment, consider: 1

• Rituximab – may be used as an alternative to splenectomy in chronic ITP or in patients who do not respond favorably to splenectomy
• High-dose dexamethasone – may also be considered as an alternative to splenectomy

Pediatric ITP: Splenectomy

Splenectomy is recommended for children and adolescents with chronic or persistent ITP who have significant or persistent bleeding and lack of responsiveness or intolerance to other therapies (corticosteroids, IVIg, anti-D) and/or who have a need for improved quality of life. 1 However, splenectomy should be delayed for at least 12 months unless accompanied by severe, life-threatening bleeding. 1

Adult ITP: Management Strategy

For adults with chronic thrombocytopenia who are asymptomatic, observation without treatment is appropriate. 2 Treatment thresholds are:

• Platelet count ≥30 × 10⁹/L with no or minor mucocutaneous bleeding: observation is recommended 2
• Platelet count <30 × 10⁹/L with no or minor mucocutaneous bleeding: corticosteroids may be considered, though observation remains acceptable depending on individual risk factors 2
• Platelet count 20,000-50,000/μL: associated with mild skin bleeding; patients should avoid contact sports and antiplatelet agents 2
• Platelet count <10,000/μL: high risk of serious hemorrhage; typically requires hospitalization and active treatment 2

For adults requiring treatment: 2

• Longer courses of corticosteroids as first-line treatment
• Intravenous immunoglobulin (IVIg) for patients who need a rapid platelet increase
• Splenectomy for patients who have failed corticosteroid therapy and have persistent bleeding risk

Secondary ITP: Specific Etiologies

When secondary causes are identified, treat the underlying condition: 2

• HCV-associated ITP: antiviral therapy should be considered in the absence of contraindications
• HIV-associated ITP: treatment of HIV infection with antiviral therapy should be considered before other treatment options
• H. pylori-associated ITP: eradication therapy should be administered

---

Critical Pitfalls to Avoid

Never diagnose ITP without personal review of the peripheral blood smear, as automated counters can miss pseudothrombocytopenia, giant platelets, or schistocytes. 2

Never omit HIV and HCV testing in adults, because these infections can masquerade as primary ITP and may precede other symptoms by years. 1, 2

Do not use medications that impair platelet function (aspirin, NSAIDs), as these increase bleeding risk even with moderate thrombocytopenia. 2

Avoid prolonged corticosteroid therapy in children due to significant toxicities including growth suppression, immunosuppression, and metabolic effects. 2

Missing thrombotic microangiopathy (TTP, HUS) or heparin-induced thrombocytopenia (HIT) carries high mortality risk (untreated TTP >90% mortality; HIT thrombosis risk 30-50%); prompt exclusion of these entities is essential. 2

---

Patient Education and Follow-Up

Provide parents and patients with emergency contact information and education about warning signs of serious bleeding: persistent epistaxis, oral bleeding, blood in stool or urine, severe headache, or altered mental status. 2

For young females of childbearing age, pregnancy management should include monitoring platelet counts throughout pregnancy, with treatment reserved for platelet counts <30 × 10⁹/L or if bleeding occurs. 2

Adolescents with ITP should avoid competitive contact sports with high risk of head trauma, and menstruation in adolescent girls should be managed with antifibrinolytic agents and hormonal contraceptives. 2