Immune Thrombocytopenic Purpura

Immune Thrombocytopenic Purpura (ITP)

Definition

Immune Thrombocytopenic Purpura (ITP) — also known as Immune Thrombocytopenia — is an acquired autoimmune disorder characterized by isolated thrombocytopenia (platelet count <100,000/µL) 

• It is a diagnosis of exclusion — no other cause of thrombocytopenia should be present.
• Hematologist Referral is must

Classification

 Epidemiology

• Children: 2–4 yrs; post-viral; often acute and self-limiting.
• Adults: 20–50 yrs; more common in women (2–3:1); Associated with chronic disease.

Pathophysiology

1. Autoantibody formation:
• IgG autoantibodies(Produced by autoreactive B cells) target platelet membrane glycoproteins — usually GPIIb/IIIa or GPIb/IX.
• Antibody-coated platelets are recognized by:splenic macrophages,hepatic macrophages,reticuloendothelial system through: Fcγ receptors.This produces accelerated platelet clearance.

3. Impaired megakaryocyte function:

• Antibodies also suppress megakaryocyte maturation → ↓ platelet production.

 Clinical Features

1. Bleeding manifestations(The relationship between platelet count and bleeding is not linear)

• Mucocutaneous bleeding:
• Petechiae, purpura, ecchymoses.
• Gum bleeding, epistaxis, menorrhagia,Hematuria
• Severe bleeding (rare): GI bleed , GU bleed, intracranial, wet Purpura(Blood blisters in mouth),retinal Hemmorhage.

2. Systemic symptoms

• Usually absent (unlike leukemia or SLE).
• No fever, lymphadenopathy, or hepatosplenomegaly (their presence suggests secondary causes).

3. Children

• Often post-viral (URI, varicella), sudden onset, self-limited within weeks.

4.Evans syndrome:ITP + autoimmune hemolytic anemia(perform combs test)

Investigations

1. Basic Tests

• Bone marrow examination is not routinely needed, only if atypical features (e.g., pancytopenia, lymph node enlargement, splenomegaly, neutropenia, leukocytosis, atypical lymphocytosis, or anemia in the presence of bone pain, fevers, or unintentional weight loss. , or poor response to therapy).

Antiplatelet antibody testing is NOT routinely recommended.

• sensitivity is limited
• specificity is imperfect
• negative test does not exclude ITP

2. Additional Tests to rule out secondary causes

• HIV, HCV serology (must be done in all adults).
• ANA if SLE suspected.
• TSH, antiphospholipid antibodies, or direct Coombs test in selected cases.
• Individuals with recurrent epigastric pain suggestive of peptic ulcer must be tested for Helicobacter pylori infection, which is a possible cause of ITP.
• No specific diagnostic test for ITP — it’s a diagnosis of exclusion.

Diagnostic Criteria (ASH 2019)

1. Isolated thrombocytopenia (<100,000/µL).
2. Normal RBC and WBC morphology.
3. No other cause of thrombocytopenia identified(Always exclude pseudothrombocytopenia before diagnosing ITP)

 Differential Diagnosis

Treatment  ITP (Adult) – ASH

The goal is NOT to normalize the platelet count so dont transfuse platelets Because transfused platelets are rapidly destroyed by circulating autoantibodies.

When should platelets be given?

• intracranial hemorrhage
• uncontrolled GI bleeding
• major surgical bleeding
• platelet count <10,000u/L

The objective is not to maintain a long-term platelet count but to provide an immediate hemostatic bridge.

1. Treatment Decision (Steroids vs Observation)

Override factors (favor steroids even if ≥30k)

• Age > 60 years
• Anticoagulant / antiplatelet use
• Planned surgery/procedure
• Significant comorbidities
• Platelets trending down

2. Admission vs Outpatient Management

3. When to Consider Admission (Even if ≥20k)

First-line Therapy

 Second-line Therapy (for steroid failure or relapse)

ASH recommendations emphasize individualized choice among TPO-RA, rituximab and splenectomy.There is no single universally “best” second-line therapy.

Refractory ITP Options

• Immunosuppressants: Azathioprine, cyclosporine, mycophenolate mofetil(500 mg orally twice daily ), cyclophosphamide.
• Fostamatinib: SYK inhibitor, approved for chronic ITP refractory to ≥2 lines of therapy.

Emergency Management

If life-threatening bleeding (e.g., intracranial, GI, severe epistaxis):

• IV methylprednisolone 1 g/day × 3 days
• IVIg 1 g/kg/day which may be repeated the next day if the platelet count remains below 50,000/μL.
• Platelet transfusion ( apheresis unit or 4 to 6 pooled platelet units.)
• Tranexamic acid

 ITP in Pregnancy

• Similar pathogenesis.
• Treat if platelet <30,000 or bleeding.
• Preferred: Prednisolone ± IVIg.
• Avoid: Rituximab, TPO agonists, splenectomy (except 2nd trimester).
• Delivery: Aim platelet >50,000/µL for vaginal; >80,000/µL for C-section.
• Maternal ITP antibodies can cross the placenta.Neonatal thrombocytopenia can occur even when the maternal platelet count is relatively good.

ITP and DVT prophylaxis

In severe thrombocytopenia:

• mechanical prophylaxis may be preferred
• pharmacologic prophylaxis depends on platelet count and bleeding status

There is no universal platelet threshold applicable to every patient.

• A practical ICU approach often considers pharmacologic prophylaxis when:platelet count is sufficiently stable, commonly ≥50 ×10⁹/L, and there is no active bleeding.But individualized assessment is essential.

 Prognosis

• Children: 80–90% recover spontaneously within 6 months.
• Adults: 20–30% have chronic disease.
• Mortality from bleeding <1%, but chronic relapsing course common.

REFERENCE

1. Pietras NM, Gupta N, Justiz Vaillant AA, et al. Immune Thrombocytopenia. [Updated 2024 May 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562282/
2. American Society of Hematology 2019 guidelines for immune thrombocytopenia
3. Mititelu A, Onisâi MC, Roșca A, Vlădăreanu AM. Current Understanding of Immune Thrombocytopenia: A Review of Pathogenesis and Treatment Options. Int J Mol Sci. 2024 Feb 10;25(4):2163. doi: 10.3390/ijms25042163. PMID: 38396839; PMCID: PMC10889445.