What are the differences in diagnosis and treatment between Immune Thrombocytopenic Purpura (ITP) and Thrombotic Thrombocytopenic Purpura (TTP)?

ITP vs TTP: Critical Diagnostic and Treatment Distinctions

Immediate Diagnostic Differentiation

The most critical distinction is that TTP is a medical emergency requiring immediate plasma exchange, while ITP is managed based on bleeding symptoms rather than platelet count alone. 1

Key Diagnostic Features

TTP (Thrombotic Thrombocytopenic Purpura):

• Presents with microangiopathic hemolytic anemia (MAHA) plus thrombocytopenia - the peripheral smear shows schistocytes, elevated LDH, decreased hemoglobin and haptoglobin 1, 2
• Caused by severe ADAMTS13 deficiency (<10% activity) due to autoantibodies that prevent cleavage of von Willebrand factor, leading to microvascular thrombosis 1, 2
• Neurologic symptoms are common (headache, confusion, seizures in 39-80% of patients) and abdominal pain occurs in 35-39% 1
• Clinical prediction score helps guide empirical treatment: platelet count <30 × 10⁹/L AND creatinine <2.0 mg/dL strongly suggests TTP 1
• Without treatment, mortality approaches 100%; with treatment, 30-day survival exceeds 90% 1

ITP (Immune Thrombocytopenic Purpura):

• Isolated thrombocytopenia (<100 × 10⁹/L) without anemia or leukopenia - peripheral smear shows normal or slightly larger platelets with normal RBC and WBC morphology 3, 4
• No schistocytes on peripheral smear - this is the key differentiating feature from TTP 4
• Physical examination is normal except for bleeding manifestations - presence of splenomegaly, hepatomegaly, or lymphadenopathy suggests secondary causes 5
• Diagnosis of exclusion requiring history, physical exam, CBC, and peripheral smear to rule out other causes 6, 3

Treatment Approaches

TTP - Immediate Life-Saving Therapy

Initiate treatment immediately when TTP is suspected, before ADAMTS13 results return:

• Therapeutic plasma exchange (TPE) is the cornerstone - removes autoantibodies and ultra-large vWF multimers while replenishing ADAMTS13 1, 7
• Corticosteroids plus rituximab should be started concurrently with TPE 1
• Caplacizumab (nanobody blocking platelet-vWF binding) reduces time to platelet normalization and decreases early recurrence risk by 29% (95% CI: 14-42%), but increases bleeding risk by 17% (95% CI: 4-30%) 1
• Continue caplacizumab until ADAMTS13 recovery to prevent early relapse 1
• Monitor ADAMTS13 activity in remission - administer rituximab when activity drops below 20% to reduce relapse risk (OR 0.09,95% CI: 0.04-0.24) 1

ITP - Symptom-Based Management

Treatment decisions are based on bleeding severity, not platelet count alone:

For adults with platelet counts <30 × 10⁹/L:

• Corticosteroids are standard initial treatment, with longer courses preferred over shorter courses 3
• IVIg (1 g/kg as single dose) when rapid platelet increase is required, repeatable if necessary 3
• Anti-D immunoglobulin is an alternative if corticosteroids are contraindicated 3

For children with platelet counts >30 × 10⁹/L:

• No treatment required if asymptomatic or only minor purpura 6
• Do not give glucocorticoids, IVIg, or anti-Rh(D) as routine initial treatment 6

For children with platelet counts <20 × 10⁹/L and significant mucous membrane bleeding OR <10 × 10⁹/L with minor purpura:

• Treat with IVIg or glucocorticoids 6

For life-threatening bleeding (ITP or TTP):

• Hospitalize immediately 6
• High-dose parenteral glucocorticoids, IVIg, AND platelet transfusions 6
• Platelet transfusions are otherwise contraindicated in ITP unless severe, life-threatening bleeding 3

Second-line ITP treatment:

• Splenectomy for patients who failed corticosteroid therapy - produces long-lasting response in majority 3
• Rituximab for patients at bleeding risk who failed first-line therapy or splenectomy 3
• Thrombopoietin receptor agonists (TPO-RAs) for patients who relapse after splenectomy or have contraindications 3

Critical Diagnostic Workup Differences

For suspected TTP:

• Send ADAMTS13 activity and inhibitor levels immediately - but do NOT wait for results before starting TPE 1, 2
• CBC with peripheral smear showing schistocytes 1, 2
• Elevated LDH, decreased haptoglobin, elevated indirect bilirubin 1
• Coagulation studies (PT, aPTT, fibrinogen, D-dimer) to exclude DIC 5

For suspected ITP:

• CBC with peripheral smear - must exclude pseudothrombocytopenia (EDTA-dependent platelet agglutination) 5, 3
• HIV, HCV, and H. pylori testing should be performed in adults 5, 3
• Bone marrow examination is NOT necessary in patients with typical ITP features 5, 3
• Bone marrow IS indicated in patients >60 years, those with systemic symptoms, abnormal signs, persistent thrombocytopenia (>6-12 months), or unresponsive to IVIg 6, 5

Common Pitfalls to Avoid

Missing TTP diagnosis:

• Failing to recognize that normal or only moderately reduced ADAMTS13 activity (>10%) excludes TTP and suggests alternative diagnoses like atypical HUS or other TMA 2
• Delaying plasma exchange while waiting for ADAMTS13 results - empirical treatment must begin immediately based on clinical prediction scores 1

Misdiagnosing ITP:

• Mistaking pseudothrombocytopenia for true ITP - always review peripheral smear 5
• Missing secondary causes - constitutional symptoms (fever, weight loss) suggest underlying disorders rather than primary ITP 5
• Overlooking drug-induced thrombocytopenia - obtain detailed medication history 5
• Not considering inherited thrombocytopenias - family history and platelet size provide critical clues 5

Treatment errors:

• Giving platelet transfusions in ITP without life-threatening bleeding - contraindicated 3
• Treating ITP based on platelet count alone rather than bleeding symptoms 6
• Performing routine bone marrow examination before initiating IVIg in typical ITP - unnecessary 6