Immune Thrombocytopenia (ITP)
Antibody-mediated platelet destruction. Diagnosis of exclusion. Most adults need treatment only if platelets < 30K or bleeding.
🔍 Overview
Overview
ITP is an autoimmune condition where IgG autoantibodies target platelet surface glycoproteins (GPIIb/IIIa, GPIb/IX), leading to splenic phagocytosis and accelerated platelet destruction. It is a diagnosis of exclusion -there is no confirmatory test. Incidence: ~3-4/100,000 adults/year. Primary ITP (80%) has no identifiable cause. Secondary ITP (20%) is associated with SLE, HIV, HCV, H. pylori, CLL, or medications (heparin → HIT, not ITP). Key principle: treat the patient, not the number. Many patients tolerate platelets of 20-30K without significant bleeding.
🧪 Workup
Workup
- CBC with peripheral smear -isolated thrombocytopenia with large platelets (young, reactive). All other cell lines normal. If pancytopenia → think MDS, aplastic anemia, infiltrative process.
- Peripheral smear -must review. Rules out pseudothrombocytopenia (platelet clumping from EDTA -redraw in citrate tube), schistocytes (TTP/HUS), blasts (leukemia), leukoerythroblastic picture (marrow infiltration).
- HIV, HCV -required in all new ITP (secondary causes that change management)
- H. pylori testing -stool antigen or breath test. Eradication can improve platelet count.
- Direct Coombs (DAT) -Evans syndrome = autoimmune hemolytic anemia + ITP. If DAT positive → treat as Evans.
- Immunoglobulins (quantitative Ig) -CVID can present with ITP
- ANA -if SLE suspected (young woman with ITP)
- Coags (PT/INR, aPTT) -should be normal. If abnormal → think DIC, liver disease, factor deficiency.
- Bone marrow biopsy -NOT routine for typical ITP. Indicated if: age > 60 (rule out MDS), atypical features (other cytopenias, splenomegaly, lymphadenopathy), or refractory to first-line therapy.
⚠️ Rule out pseudothrombocytopenia FIRST (before working up any isolated low platelet count). It is a lab artifact, not a real low count: EDTA in the lavender CBC tube chelates calcium, exposing a cryptic epitope on platelet GPIIb/IIIa that naturally occurring antibodies (usually IgG) bind, clumping the platelets in vitro. The analyzer counts each clump as one particle (or skips it), so it reports a falsely low number. The patient’s true count is normal and they are not bleeding, the tip-off is severe “thrombocytopenia” with no clinical correlate.
- Confirm on the peripheral smear (the diagnostic manual step), platelet clumps, classically at the feathered edge. Seeing clumps tells you the automated count is spurious.
- Can you just do a manual count? Only on a non-clumped specimen. A manual hemocytometer count run on the same clumped EDTA tube is also falsely low, because aggregated platelets cannot be counted as singles by any method, automated or manual. The clumps have to be prevented first.
- Get an accurate count by removing the clumping: redraw in sodium citrate (blue top) and multiply the result by 1.1 to correct for the citrate dilution; or use heparin (green top); and/or warm the sample to 37°C and run promptly (some cases are cold-dependent). Then either automated or manual counting is reliable.
- Why it matters: mistaking pseudothrombocytopenia for true thrombocytopenia leads to unnecessary platelet transfusions, steroids, marrow biopsies, and held anticoagulation. The fix is changing the tube, not treating the patient.
🚨 Management
Management
- Observation only if platelets ≥ 30K and no bleeding and no upcoming procedures -most patients don't need treatment. ASH Guidelines, 2019
- First-line -Corticosteroids:
- Dexamethasone 40 mg PO daily × 4 days -preferred by many experts. Faster response, shorter course. Can repeat q2-4 weeks × 3-4 cycles. Wei, 2016
- Prednisone 1 mg/kg daily × 2-4 weeks → taper. Classic approach. Response in 70-80% but relapse rate ~60-80% after taper.
- First-line adjunct -IVIG 1g/kg × 1-2 days: for active bleeding or platelets < 10K or pre-procedure. Fastest response (24-48h) but transient (2-4 weeks). Fc receptor blockade → reduced splenic phagocytosis.
- Anti-D (WinRho) 50-75 mcg/kg IV: only for Rh-positive, non-splenectomized patients. Causes mild extravascular hemolysis that "distracts" the spleen. FDA black box: rare fatal intravascular hemolysis.
- Second-line -TPO receptor agonists: Eltrombopag 50 mg PO daily or Romiplostim 1-10 mcg/kg SQ weekly. Stimulate megakaryopoiesis. ~80% response. Maintenance therapy -platelets drop when stopped. RAISE, 2011; EXTEND
- Second-line -Rituximab 375 mg/m² weekly × 4: ~60% initial response but only ~20-30% sustained at 5 years. Best in younger patients with short disease duration.
- Second-line -Fostamatinib (SYK inhibitor): 100-150 mg BID PO. For refractory ITP. FIT, 2018
- Third-line -Splenectomy: ~65% long-term remission. Defer at least 12-24 months (spontaneous remission possible). Requires pre-op vaccines (pneumococcal, meningococcal, Hib) ≥ 2 weeks before surgery.
- Emergency bleeding: Platelets + IVIG + methylprednisolone 1g IV + aminocaproic acid (antifibrinolytic). Consider emergent splenectomy if refractory.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Dexamethasone | 40 mg daily × 4 days | PO | Preferred first-line. Can repeat q2-4 wk. Wei, 2016 |
| Prednisone | 1 mg/kg × 2-4 wk → taper | PO | Alternative first-line. 70-80% response. High relapse on taper. |
| IVIG | 1 g/kg × 1-2 days | IV | Fastest response (24-48h). For bleeding or plt < 10K. Transient. Monitor for infusion reactions, aseptic meningitis. |
| Eltrombopag | 50 mg daily (titrate 25-75) | PO | TPO-RA. Response in 1-2 wk. Monitor LFTs. Take on empty stomach (no dairy/Ca). RAISE, 2011 |
| Romiplostim | 1-10 mcg/kg weekly | SQ | TPO-RA. Titrate by platelet response. Risk of marrow reticulin fibrosis (reversible). |
| Rituximab | 375 mg/m² weekly × 4 | IV | Anti-CD20. 60% initial response, ~25% durable at 5y. Check HBV before. Arnold, 2007 |
| Fostamatinib | 100-150 mg BID | PO | SYK inhibitor for refractory ITP. SE: diarrhea, HTN, LFT elevation. FIT, 2018 |
| Aminocaproic acid | 4-5g load → 1g/hr | IV/PO | Antifibrinolytic for emergency bleeding. Adjunct to platelets. |
🏥 Rounds
Sample Presentation
Mrs. Patel is a 34-year-old woman presenting with 3 days of spontaneous bruising and petechiae on bilateral lower extremities. No mucosal bleeding, no epistaxis, no hemoptysis, no melena. No recent illness or new medications. No joint pains or rash. VS stable. Exam: scattered petechiae on shins, no splenomegaly, no lymphadenopathy. Labs: platelets 8K (previously normal 6 months ago), Hgb 13.2, WBC 6.8, peripheral smear shows large platelets with no schistocytes/blasts. PT/INR normal. HIV negative, HCV negative, H. pylori stool antigen negative. DAT negative.
Key Points: Isolated thrombocytopenia with large platelets and otherwise normal CBC + smear = classic ITP. Plt < 10K with mucosal bleeding risk → start IVIG 1g/kg + dexamethasone 40 mg × 4 days. No need for bone marrow biopsy in a young patient with typical presentation.
Pimp Questions
❓ What is the platelet threshold for treatment in ITP?
Platelets < 30K or any clinically significant bleeding, regardless of count. Treat the patient, not the number. Many patients tolerate 20-30K without bleeding. ASH Guidelines, 2019
❓ What must you always check on the peripheral smear before diagnosing ITP?
Rule out pseudothrombocytopenia (EDTA-induced platelet clumping -redraw in citrate tube), schistocytes (TTP/HUS/DIC), blasts (leukemia), and leukoerythroblastic picture (marrow infiltration). ITP should show large platelets and nothing else abnormal.
❓ When do you give IVIG vs steroids alone in ITP?
IVIG 1 g/kg for: active bleeding, platelets < 10K, or pre-procedure urgent platelet rise needed. IVIG works in 24-48 hours (fastest). Steroids alone are adequate for stable patients with plt 10-30K and no active bleeding. IVIG effect is transient (2-4 weeks).
❓ What is Evans syndrome?
Evans syndrome = autoimmune hemolytic anemia (AIHA) + ITP. Positive direct Coombs test + thrombocytopenia. More aggressive course than ITP alone. Often associated with SLE or lymphoproliferative disorders. Treatment: steroids, rituximab. Check DAT in all ITP patients.
❓ What vaccines are required before splenectomy for ITP?
Pneumococcal (PCV20 or PCV15 + PPSV23), meningococcal (MenACWY + MenB), and Haemophilus influenzae type b (Hib). Give ≥ 2 weeks before surgery. Post-splenectomy: lifelong risk of overwhelming post-splenectomy infection (OPSI) from encapsulated organisms.
❓ What are TPO receptor agonists and when do you use them?
Eltrombopag (oral, daily) and romiplostim (SQ, weekly) stimulate megakaryopoiesis via the thrombopoietin receptor. Second-line for chronic ITP failing steroids. ~80% response rate. Maintenance therapy -platelets drop when stopped. Monitor LFTs (eltrombopag) and for reticulin fibrosis (both). RAISE, 2011
❓ When do you perform a bone marrow biopsy in ITP?
NOT routine. Indications: (1) age > 60 (rule out MDS), (2) atypical features (other cytopenias, splenomegaly, lymphadenopathy, abnormal smear), (3) refractory to first-line therapy, (4) before splenectomy (some centers). In typical young-adult ITP with isolated thrombocytopenia, diagnosis is clinical.
❓ What is "wet purpura" and why is it important?
Wet purpura = hemorrhagic bullae (blood blisters) in the oral mucosa. It indicates a higher risk of serious hemorrhage compared to dry purpura (skin-only petechiae/ecchymoses). Wet purpura with plt < 10K is an indication for urgent treatment with IVIG + high-dose steroids.
Clinical Examples
📋 Case 1, Newly Diagnosed ITP with Severe Thrombocytopenia
Patient: 28F with petechiae on legs, gum bleeding, and menorrhagia × 1 week. Platelets 8K. WBC and Hgb normal. Smear: large platelets, no schistocytes. No splenomegaly. No meds.
Key findings: Isolated thrombocytopenia in a young woman with no other cytopenias and normal smear = classic ITP. Large platelets = increased marrow production (compensatory). No schistocytes rules out TTP/HUS.
Management:
- Dexamethasone 40 mg daily × 4 days (preferred over prednisone taper, faster response, shorter course)
- IVIG 1 g/kg × 1-2 days if wet purpura or active mucosal bleeding (raises platelets within 24-48h)
- Avoid platelet transfusion unless life-threatening bleeding (transfused platelets destroyed immediately)
- Hold anticoagulants, avoid NSAIDs, IM injections, contact sports
- Check HIV, HCV, H. pylori (treatable causes of secondary ITP)
Teaching point: ITP is a diagnosis of exclusion, there is no confirmatory test. The goal is NOT a normal platelet count; it's a safe count (≥ 30K in most patients). Overtreating asymptomatic mild ITP causes more harm than the disease.
📋 Case 2, Chronic Refractory ITP
Patient: 52F with ITP × 3 years. Failed steroids (relapsed after taper × 3), failed rituximab. Currently on romiplostim 5 mcg/kg weekly, platelets fluctuate 15-40K. Now needs hip replacement. Surgeon wants platelets > 50K.
Key findings: Chronic refractory ITP requiring pre-surgical platelet optimization. Bone marrow biopsy showed megakaryocytic hyperplasia (appropriate for ITP). No MDS features.
Management:
- Increase romiplostim to 8-10 mcg/kg weekly (titrate to target > 50K for surgery)
- Add IVIG 1 g/kg 1-2 days pre-op for rapid temporary boost
- Platelet transfusion available in OR (transfuse only for active surgical bleeding)
- Consider eltrombopag 50-75 mg daily as add-on or alternative TPO-RA
- TXA 1g IV pre-op + 1g q8h × 3 days post-op (antifibrinolytic, reduces surgical bleeding)
Teaching point: TPO receptor agonists (romiplostim, eltrombopag) are the backbone of chronic ITP management. They work in ~80% of patients but require ongoing therapy, platelets drop when stopped. For surgery, combine TPO-RA dose escalation + IVIG for reliable platelet elevation.
📋 Case 3, ITP with Life-Threatening Intracranial Hemorrhage
Patient: 65M with known ITP (non-compliant with eltrombopag). Presents with sudden severe headache, vomiting, right hemiplegia. CT head: left basal ganglia hemorrhage with midline shift. Platelets 3K.
Key findings: ICH in the setting of severe thrombocytopenia, life-threatening emergency. Mortality of ICH with plt < 10K approaches 50%. This is one of the few situations where platelet transfusion is indicated in ITP.
Management:
- Platelet transfusion: 2-3 adult doses STAT (even though destroyed rapidly, provides temporary hemostasis)
- IVIG 1 g/kg IV STAT (raises endogenous platelets within 24-48h by blocking Fc receptors on splenic macrophages)
- Methylprednisolone 1g IV daily × 3 days
- TXA 1g IV (antifibrinolytic, stabilizes existing clot)
- Emergent neurosurgery consult for possible decompressive craniotomy
Teaching point: ICH is the most feared complication of ITP (< 1% but devastating). In this scenario, transfuse platelets despite ITP, the immediate hemostatic need outweighs the short platelet lifespan. Combine with IVIG and steroids for sustained response.
Monitoring
- Platelet count -q1-2 days during active treatment; weekly during titration; monthly once stable. Goal: ≥ 30K (not "normal").
- Bleeding assessment -skin (petechiae, purpura, ecchymoses), mucosal (oral blood blisters = "wet purpura" = higher bleed risk), menorrhagia, epistaxis, GI, intracranial
- Blood glucose -while on steroids (dexamethasone/prednisone)
- LFTs -q2-4 weeks on eltrombopag (hepatotoxicity risk)
- CBC with differential -monitor for new cytopenias (would suggest secondary cause or MDS)
- Reticulin fibrosis -consider bone marrow biopsy if on TPO-RA > 1 year (rare reversible marrow fibrosis)
- Infection screening -on immunosuppression (rituximab, chronic steroids). HBV reactivation monitoring with rituximab.
📋 Summary
Summary
Rule Out the Artifact First
Pseudothrombocytopenia before anything else. EDTA in the lavender CBC tube chelates calcium, exposing an epitope on platelet GPIIb/IIIa, and the platelets clump, so the analyzer counts them as one. Repeat in a citrate or heparin tube and look at the smear for clumps. Working up an artifact is the commonest wasted workup in hematology.
It Is a Diagnosis of Exclusion
Isolated thrombocytopenia with a normal white count, normal hemoglobin and an otherwise normal smear. Exclude the alternatives: drugs (heparin, quinine, sulfonamides, vancomycin, linezolid), infection (HIV, HCV, H. pylori, EBV, CMV), liver disease with splenic sequestration, lymphoproliferative disorders, lupus and antiphospholipid syndrome, TTP and DIC. An antiplatelet antibody test is not useful and should not be ordered.
Treat the Bleeding Risk, Not the Number
Most adults need treatment only for platelets below 30,000 or for bleeding. Above 30,000 without bleeding, observe: the risk of the treatment exceeds the risk of the count. Wet purpura, mucosal or GI bleeding, is far more concerning than petechiae and is what should escalate management.
First Line Is a Steroid
Dexamethasone 40 mg daily for 4 days is preferred, repeatable every 2 to 4 weeks, with faster responses and less cumulative toxicity than a long prednisone taper. Prednisone 1 mg/kg for 2 to 4 weeks then taper is the alternative, with 70 to 80% responding but a high relapse rate on the taper. Do not keep a patient on chronic steroids to hold a count: move to a second-line agent instead.
IVIG for Speed
1 g/kg for 1 to 2 days, giving a response in 24 to 48 h. Use it when there is bleeding, before an urgent procedure, or with a platelet count below 10,000, because steroids take days. The effect is transient, so it buys time rather than treating the disease, and it is given alongside a steroid rather than instead of one. Anti-D is an alternative in Rh-positive, non-splenectomized patients.
Second Line Has Genuinely Changed
Thrombopoietin receptor agonists (eltrombopag, romiplostim) and rituximab have largely displaced early splenectomy. TPO agonists work in most patients but usually need to be continued, and eltrombopag has to be separated from calcium and food. Splenectomy still gives the highest durable remission rate but is now deferred at least 12 months, and requires encapsulated-organism vaccination beforehand.
Transfuse Platelets Only for Serious Bleeding
Transfused platelets are destroyed by the same antibody within hours, so a routine transfusion for a low number achieves nothing. Reserve them for life-threatening bleeding, given with IVIG, where the goal is a brief hemostatic window rather than a corrected count.
Special Situations
Pregnancy: distinguish ITP from gestational thrombocytopenia (mild, third trimester, no fetal effect) and from preeclampsia or HELLP; steroids and IVIG are the safe options and the platelet count needed depends on the delivery mode and the anesthetic plan. Test for HIV and HCV in every adult, because both cause ITP and both are treatable at the cause. Secondary ITP from lupus or CLL is treated by treating the underlying disease.
📄 One Pager
Text version
One-Pager
ITP
Immune Thrombocytopenia
Diagnosis
Isolated thrombocytopenia + large platelets on smear. Normal WBC/Hgb. Rule out: pseudothrombocytopenia (EDTA clumping), TTP (schistocytes), DIC (fibrinogen), HIT (heparin exposure), drug-induced. Check HIV, HCV, H. pylori, DAT.
Treatment Algorithm
Plt ≥ 30K no bleeding → observe. Plt < 30K or bleeding → dexamethasone 40 mg × 4d ± IVIG if severe. Refractory → TPO-RA (eltrombopag/romiplostim) or rituximab. Last resort → splenectomy (vaccinate first).
Key Drugs
IVIG 1g/kg (fastest, 24-48h, transient). Dexamethasone 40 mg × 4d. Eltrombopag 50 mg PO daily. Romiplostim 1-10 mcg/kg SQ weekly. Rituximab 375 mg/m² × 4. Aminocaproic acid for emergency bleeding.
Related Topics
Acute Leukemia (AML / ALL)AmyloidosisAnemia WorkupAnemia WorkupAnticoagulation ManagementChemotherapy Toxicities