Idiopathic Thrombocytopenic Purpura: Comprehensive Management
Definition and Diagnosis
ITP is a diagnosis of exclusion characterized by isolated thrombocytopenia (platelet count <100,000/μL) without other hematologic abnormalities, splenomegaly, or identifiable secondary causes. 1, 2
Key Diagnostic Elements
History must specifically assess:
- Bleeding type, severity, and duration (mucocutaneous bleeding suggests platelet disorder) 1
- Medication exposure to quinidine, heparin, sulfonamides, sulfonylureas, dipyridamole, or salicylates 2
- HIV risk factors and symptoms of autoimmune disorders (arthralgias, rash, alopecia) 1
- Prior hemostasis with surgeries or pregnancies 1
- Family history of thrombocytopenia or autoimmune conditions 1
Physical examination must identify:
- Bleeding signs including retinal hemorrhages 1
- Absence of splenomegaly (present in <3% of true ITP cases; its presence suggests alternative diagnosis) 2
- Signs of infection (bacteremia, HIV), liver disease, or autoimmune disorders 1
- Neurologic abnormalities that might suggest thrombotic thrombocytopenic purpura 1
Essential laboratory workup:
- Complete blood count with peripheral smear examination to confirm true thrombocytopenia and exclude pseudothrombocytopenia from EDTA-induced platelet clumping 2
- HIV and hepatitis C testing for at-risk patients 1, 3
- Helicobacter pylori screening (urea breath test, stool antigen, or endoscopic biopsy) as eradication therapy improves platelet counts 1
Bone marrow examination is NOT routinely indicated but consider for:
- Atypical features or failure to respond to initial therapy 3
- Persistent thrombocytopenia >6-12 months 2
- Age >60 years or concern for myelodysplastic syndrome 1
Clinical Course and Prognosis
Adults vs. Children
ITP in adults is typically chronic with an estimated 5% fatal hemorrhage rate (primarily intracranial), though modern supportive care has likely reduced this mortality. 1 In contrast, children frequently experience spontaneous remission. 1
- Spontaneous complete remission occurs in only ~5% of adults after failing glucocorticoids and splenectomy 1
- Hemorrhagic complications increase with age at equivalent platelet counts 1
- Children with typical ITP presentation have high rates of spontaneous remission, particularly within the first 6 months 1, 3
Treatment Algorithm
Initial Management Decision
Observation alone is recommended for patients with no bleeding or only mild bleeding (skin manifestations like petechiae/purpura), regardless of platelet count. 2 This applies to both adults and children with platelet counts >30,000/μL who are asymptomatic. 4, 3
Treatment is indicated for:
- Platelet count <10,000/μL with minor purpura 4
- Platelet count <20,000/μL with significant mucous membrane bleeding 4
- Any platelet count with active severe bleeding 2
- Patients requiring procedures or at high risk for trauma 1
First-Line Treatment Options
For patients requiring treatment, choose from three equally effective first-line options: 1, 2
Intravenous immunoglobulin (IVIg): Single dose 0.8-1 g/kg 1, 2
- Rapid platelet increase (within 24-48 hours)
- Preferred for urgent situations or active bleeding
- Expensive; effects are temporary (2-4 weeks)
Corticosteroids: Short course 1, 2
- Prednisone 1 mg/kg/day or equivalent
- Response typically within 3-7 days
- Taper after platelet response achieved
- Avoid prolonged use due to cumulative toxicity
Anti-D immunoglobulin: Single dose in Rh-positive, non-splenectomized patients 1, 2
- Less expensive than IVIg
- Only effective in Rh-positive patients with intact spleen
- Monitor for hemolysis
Critical pitfall: Avoid platelet transfusions for isolated thrombocytopenia without active bleeding, as transfused platelets are rapidly destroyed and may worsen autoimmune response. 4
Second-Line and Chronic ITP Management
When First-Line Therapy Fails
For patients at risk of bleeding who have failed one line of therapy (corticosteroids or IVIg) and have not had splenectomy, consider: 1
Rituximab (anti-CD20 monoclonal antibody): 375 mg/m² weekly × 4 doses 1
- Response rate ~60% but often temporary
- May delay or avoid splenectomy
High-dose dexamethasone: 40 mg daily × 4 days, repeated monthly 1
- Higher response rates than conventional steroids
- Shorter exposure to steroid side effects
Splenectomy
Splenectomy should be considered for patients with persistent symptomatic thrombocytopenia after failing medical therapy, but delay for at least 12 months after diagnosis in children to allow for spontaneous remission. 1, 3
- Laparoscopic and open splenectomy offer similar efficacy 1
- Response rate: 61% durable response in non-splenectomized adults, 38% in previously splenectomized patients 5
- Vaccinate against encapsulated organisms (pneumococcus, meningococcus, Haemophilus influenzae) at least 2 weeks before splenectomy 1
Post-splenectomy management:
- No further treatment needed if platelet count >30,000/μL and asymptomatic 1
- For persistent thrombocytopenia, consider thrombopoietin receptor agonists
Thrombopoietin Receptor Agonists
For chronic refractory ITP after splenectomy or in patients who are not surgical candidates, thrombopoietin receptor agonists are highly effective: 5
Romiplostim (Nplate): Weekly subcutaneous injection starting at 1 mcg/kg, titrated to maintain platelets 50,000-200,000/μL 5
- Overall platelet response: 88% in non-splenectomized, 79% in splenectomized patients 5
- Median dose: 2-3 mcg/kg weekly 5
- Warning: Risk of thrombosis if platelet count becomes excessively elevated; requires weekly platelet monitoring initially, then monthly once stable 5
- Contraindicated in myelodysplastic syndrome 5
Eltrombopag: Oral alternative with similar efficacy 6
These agents stimulate platelet production rather than suppress immune destruction, representing a paradigm shift in ITP management. 7, 6
Special Populations
Pregnancy
Pregnant women with ITP require treatment only for: 1, 2
- Platelet count <10,000/μL at any time
- Platelet count 10,000-30,000/μL with bleeding in second/third trimester
- Platelet count <50,000/μL approaching delivery
First-line treatment options: 1
- Corticosteroids (prednisone preferred over dexamethasone due to placental metabolism)
- IVIg
Mode of delivery should be based on obstetric indications, not maternal platelet count. 1 Cesarean section does not reduce neonatal bleeding risk.
Neonatal management:
- Check cord blood platelet count at delivery 4
- Perform brain ultrasound if neonatal platelet count <20,000/μL or 20,000-50,000/μL even without neurologic symptoms 4
Secondary ITP
HIV-associated ITP:
- Treat underlying HIV infection with antiretroviral therapy first, unless clinically significant bleeding complications are present 1
- If ITP treatment needed: corticosteroids, IVIg, or anti-D as first-line 1
- Splenectomy preferred over other agents for refractory cases 1
Hepatitis C-associated ITP:
- Consider antiviral therapy in absence of contraindications 1
- Monitor platelet count closely as interferon may worsen thrombocytopenia 1
- If ITP treatment required: IVIg preferred as first-line 1
H. pylori-associated ITP:
- Administer eradication therapy (triple or quadruple therapy) to all ITP patients testing positive for H. pylori 1
- Platelet response occurs in 50-60% of infected patients after eradication
- Screen all ITP patients in regions with high H. pylori prevalence 1
Medications and Activities to Avoid
Strictly avoid:
- Aspirin and NSAIDs (exacerbate bleeding) 1, 3
- Contact sports and high-risk activities for trauma 3
- Intramuscular injections when platelet count <50,000/μL
For adolescent females with ITP:
- Educate on menstrual management 3
- Consider antifibrinolytic agents (tranexamic acid) and hormonal contraceptives to reduce menstrual bleeding 3
Monitoring Requirements
During active treatment:
After discontinuing treatment:
- Platelet counts at least twice weekly for 2 weeks to detect rebound thrombocytopenia 5
Long-term surveillance: