23 Immune Thrombocytopenia
- ITP: Plt <150K, dx of exclusion, diagnosis largely clinical
- Initial eval: CBC, smear, serologies (HCV, HP, ANA, RPR), DAT
- Tx threshold: Plt <30K, active bleeding, or planned surgery
- 1st-line: Prednisone 0.5–1 mg/kg ×4–6 wk → taper; IVIg 1–2 g/kg; TPO-RAs
- 2nd-line: Splenectomy (60–70% remission), rituximab, BTK inhibitors
- Pregnancy: Passive IgG transfer risk; vaginal delivery ok if plt ≥50K
23.1 Diagnosis
ITP definition - Plt <150K w/o splenomegaly, lymphadenopathy, other cytopenias - Dx of exclusion; platelet-bound IgG in most but not all - Prevalence 1:300–400 (adults), 1:1000–3000 (children) - Acute (post-viral, children) vs. chronic (adults); rare severe bleed at dx
Classification | Course | Duration | Features | |——–|———-|———-| | Newly diagnosed | <3 mo | Early presentation | | Persistent | 3–12 mo | Ongoing tx required | | Chronic | >12 mo | Long-term management | | Remission | Any | Plt ≥150K × ≥30d off tx | | Response | Any | Plt ≥30K & ≥2× baseline | : ITP Classification {.striped}
Rule out secondary causes - Drugs: NSAIDs, TMP-SMX, quinine, heparin - Infection: HCV, H. pylori, HIV, CMV, EBV, parvovirus - Autoimmune: SLE, APS, Evans (AIHA + ITP) - Heme: TTP, HUS, DIC, MAHA - Lymphoproliferative: CLL, lymphoma - Other: Splenomegaly (cirrhosis), pregnancy
23.2 Clinical Presentation
Symptoms - Often asymptomatic on routine CBC - Petechiae, purpura, mucous membrane bleeding, epistaxis - GI/GU bleeding, heavy menses - Intracranial hemorrhage rare (~1%), risk ↑ w/ plt <10K & active bleed
Exam - Usually normal; no splenomegaly or lymphadenopathy - No correlation between plt count & bleeding risk - Baseline hemostatic capacity varies widely
23.3 Evaluation
Lab workup - CBC w/ differential & smear: Confirm plt reduction, assess RBC/WBC, r/o pseudothrombocytopenia - Serologies: HCV ab/RNA, HP serology, ANA, RPR, DAT - Optional: HSV/CMV/EBV/parvovirus PCR if indicated - Coagulation: PT/INR, aPTT if bleeding present - BM biopsy: NOT routine; consider if age >60, atypical presentation, concern for MDS/lymphoproliferation, pre-splenectomy
HCV & H. pylori - HCV: 5–10% ITP; SVR w/ DAAs may improve plt - H. pylori: Eradication improves plt in 15–30%; test endemic areas
23.4 Treatment Overview
Tx thresholds & initiation - Plt <30K, active bleeding, or elective surgery = treat - Asymptomatic plt 30–50K = usually observe - Plt ≥50K = no tx needed (unless other indication) - Corticosteroid-sparing: IVIg + low-dose CS together; transition TPO-RA early
- Pregnancy: Passive IgG transfer; fetal/neonatal plt <1% severe bleed; vaginal delivery ok if maternal plt ≥50K
- Splenectomy: 60–70% durable remission; steroid-dep or -ref candidates; 10–15% partial response; ~25% fail; ~50% relapse ≥5y
- Corticosteroid dependence: Most develop steroid dep or resistance; transition early to TPO-RA or splenectomy
23.5 First-Line Treatment
Prednisone/Methylprednisolone - Mechanism: ↓ Anti-plt ab, block Fc-mediated destruction, ↑ Treg - Dosing: Prednisone 0.5–1 mg/kg/d ×4–6 wk → taper 5–10 mg/wk - Methylpred: 1–2 mg/kg/d; similar duration - Response: 80–90% achieve plt >50K; onset 1–2 wk - Monitor: CBC baseline, 1 wk, then weekly; taper slow (relapse risk) - AE (chronic): HTN, hyperglycemia, infection, bone loss, avascular necrosis
IVIg - Mechanism: FcγRIIB saturation on splenic macrophages - Dosing: 1–2 g/kg IV ×1–5d (divided), repeat as needed - Onset: 24–72h; peak 3–7d; duration 2–4 wk - Use: Urgent increment (bleed, surgery, pregnancy); concurrent CS; CS intolerant - Limits: Cost, tachyphylaxis, thromboembolism risk, TRALI, hypernatremia, headache
Anti-D Ig (Rho(D) Immune Globulin) - Dosing: 50–75 μg/kg IV (typical 500 IU/kg) - Mechanism: Coat RBCs; splenic macrophages spare platelets - Onset: 3–5d (similar to IVIg) - Limits: Rh D+ & intact spleen only; hemolysis risk; less efficacy than IVIg; cheaper
23.6 Second-Line Treatment
Splenectomy - Success: 60–70% durable remission (plt >50K ≥6 mo off tx) - Candidates: CS-dependent or -refractory (plt <50K despite 1–2 mg/kg ×4 wk) - Predictors: Female, age >40, <30y disease, acute onset, good initial CS response - Procedure: Lap preferred; vaccinate (PCV, MCV, Hib) pre-op - Outcomes: 10–15% partial; ~25% fail; ~50% relapse ≥5y
Rituximab - Mechanism: Anti-CD20; deplete B cells → ↓ anti-plt ab - Dosing: 375 mg/m² IV weekly ×4 weeks - Response: 50–60% initial; median duration 3–6 mo; ~20–30% long-term remission - Indication: CS-dep or -ref; combine w/ other agents - Monitor: CBC, Ig (baseline, periodic); PML rare (~1:25K non-malig); HBV reactivation
TPO-Receptor Agonists (TPO-RAs) - Mechanism: Bind c-MPL; ↑ megakaryopoiesis & plt production (immune-independent)
| Agent | Route | Starting | Typical | Notes |
|---|---|---|---|---|
| Romiplostim | SC weekly | 1 μg/kg | 1–10 μg/kg | Increase 1 μg/kg q1–2 wk; plt ceiling ~300K |
| Eltrombopag | PO daily | 50 mg | 25–150 mg | Monitor LFTs; hepatotoxicity ⚠ |
| Avatrombopag | PO daily | 20 mg | 20 mg | Short half-life; rapid on/off |
| Lusutrombopag | PO daily | 3 mg | 3 mg | Pre-procedural & chronic ITP |
- Response: 80–90% achieve plt >50K; onset 4–7d; off → nadir 5–7d
- Advantages: Effective CS-dep/-ref; taper/d/c CS; oral improves adherence
- Limits: Cost, thromboembolism risk (esp. high baseline plt), BM reticulin (reversible), hepatotox (eltrom), drug interactions
23.7 Third-Line & Emerging
Azathioprine & Mycophenolate - Azathioprine: 1–2 mg/kg/d; response weeks–months; CS-sparing effect - Mycophenolate: 1–1.5 g BID; limited data; fewer drug interactions - Both slower than CS; combine w/ low-dose steroids
Belimumab - Anti-BAFF ab; inhibit B cell survival & maturation - Limited data; case reports suggest benefit in ref ITP - Cost & availability limit routine use
ATG & Cyclosporine - ATG: 3–5 mg/kg ×3–5d; ~50% ref ITP response; immunosup & serum sickness concerns - Cyclosporine: 5 mg/kg/d (divided); variable response; TDM required
Emerging (Clinical Trials) - BTK inhibitor (fostamatinib): Syk inhib; ↑ plt production, ↓ ab-mediated destruction - FcγRIIB antagonists: Block inhibitory Fc receptor signaling - Syk inhibitors: ↓ Plt destruction via multiple mechanisms
23.8 Severe Bleeding & Urgent Situations
Acute severe bleed - Plt transfusion: 1 unit/10 kg (typical 4–6 units); give immediately w/ medical tx - High-dose CS: Methylpred 1–2 g IV ×1–3d → oral prednisone - IVIg: 1–2 g/kg IV ×1–5d (slower onset than transfusion) - Anti-D: If Rh D+ w/ intact spleen - FFP: Concurrent coagulopathy/DIC; reserve for plt <10K w/ bleed - Tranexamic acid: 0.5–1 g IV q6–8h or 1 g PO TID (mucosal/GI bleed) - Upper endoscopy: GI bleed refractory to medical tx; laser/cautery if no lesion
Pregnancy - Maternal tx: Standard ITP tx; goal plt ≥50K at delivery - Fetal/neonatal: Passive IgG transfer; fetal plt <1%; severe neonatal bleed <1% - Delivery: Vaginal ok if maternal plt ≥50K; C/S if <50K - Neonatal: CBC at birth; treat plt <50K w/ IVIg or observe
23.9 Monitoring & Follow-Up
Baseline - CBC, smear, serologies, DAT, ±HSV/CMV/EBV/parvovirus
On therapy - CBC weekly during induction; less frequent during maintenance - TPO-RA: Monthly CBC initially, then q3–6 mo; annual LFTs (eltrom); annual BM fibrosis assessment - Pre-splenectomy: Vaccinate encapsulated organisms (PCV, MCV, Hib) ≥2 wk pre-op
Patient education - Bleed symptom recognition, medication adherence - Avoid NSAIDs & antiplatelet agents - Safe sexual/contact practices
23.10 Response & Resistance
Definitions - Response: Plt >50K sustained ≥1 mo on tx - Remission: Plt >50K sustained ≥6 mo off tx - Refractory: Plt <50K despite adequate tx (CS, IVIg, ±splenectomy)
IVIg/Anti-D resistance → ↑ IgG requirement, rapid clearance, altered Fc saturation; consider T cell dysfunction
Refractory ITP management 1. Confirm dx (r/o secondary, pseudothrombocytopenia) 2. Assess hemostasis (bleed risk) 3. Combine tx (low-dose prednisone + TPO-RA + rituximab) 4. Splenectomy if not done 5. Clinical trials (BTK, Syk, FcγRIIB inhibitors)