Immune Thrombocytopenic Purpura (ITP)

Content of This Page

1- Introduction

2- Pathophysiology

3- Genetics & Inheritance

4- Clinical Features

5- Investigations

6- Treatment

7- Prognosis & Follow-up

Introduction

Immune Thrombocytopenic Purpura (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia (low platelet count) due to immune-mediated destruction of platelets. It may present as either an acute, self-limiting illness (especially in children) or a chronic, relapsing condition in adults.

The hallmark feature of ITP is mucocutaneous bleeding (e.g. petechiae, purpura, easy bruising), though many patients are asymptomatic. Diagnosis is one of exclusion, meaning other causes of thrombocytopenia must be ruled out.

Pathophysiology

1. Autoantibody Formation

Autoantibodies (mainly IgG) are produced against glycoproteins on the platelet surface, particularly:
- GpIIb/IIIa
- GpIb/IX
- These antibodies are usually generated by autoreactive B cells and may be triggered by infections, vaccines, or autoimmune diseases.

2. Platelet Destruction

Antibody-coated platelets are cleared by macrophages in the reticuloendothelial system, especially in the spleen.
This leads to shortened platelet lifespan, often reduced to a few hours (normal = ~7–10 days).

3. Impaired Platelet Production

In addition to peripheral destruction, autoantibodies may also target megakaryocytes in the bone marrow.
This impairs platelet production, compounding the thrombocytopenia.

4. T-Cell Dysregulation

Emerging evidence suggests a role for cytotoxic T cells, which may directly damage platelets or megakaryocytes.
There is also reduced regulatory T cell activity, contributing to immune dysregulation.

Genetics & Inheritance

1. Is ITP Inherited?

No, ITP is not directly inherited.
Most cases are sporadic and occur without a family history.
However, familial clustering has been reported, suggesting a genetic predisposition in some individuals.

2. Genetic Susceptibility Factors

Certain genetic factors may increase susceptibility to ITP or influence disease course:

Genetic Feature	Role
HLA Class II alleles	Associated with increased risk of autoantibody production (e.g. HLA-DRB1 variants)
Polymorphisms in immune genes	Affect T-cell regulation and B-cell activity (e.g. CTLA-4, TNF-α)
Fc receptor gene variants	Influence how antibody-coated platelets are cleared

3. Familial ITP (Rare)

Extremely rare familial forms of ITP exist, especially in paediatric cases.
May overlap with inherited thrombocytopenic syndromes, but these are usually non-immune in mechanism and require careful diagnostic distinction.

4. Related Autoimmune Background

ITP may occur more frequently in individuals with a personal or family history of autoimmune diseases, such as:
- Systemic lupus erythematosus (SLE)
- Autoimmune thyroid disease
- Type 1 diabetes mellitus
- This suggests a shared genetic susceptibility to autoimmunity, not specific inheritance of ITP itself.

Clinical Features

System Affected	Clinical Features
Skin	Petechiae, purpura, ecchymoses
Mucosa	Epistaxis, gum bleeding, menorrhagia
GI/Urinary	Melaena, haematuria
CNS	Rare: headache, neurological signs (due to ICH)
Systemic exam	Usually normal; no splenomegaly or lymphadenopathy

Investigations

Purpose	Tests
Confirm isolated thrombocytopenia	FBC, blood film
Exclude secondary causes	HIV, HCV, ANA, H. pylori
Rule out mimics	Coagulation tests, bone marrow (if needed)
Detect associated conditions	Direct Coombs, flow cytometry (selected cases)

Treatment

Stage	Treatment Options
First-line	Corticosteroids, IVIG
Second-line	Rituximab, splenectomy, TPO agonists
Emergency / bleeding	IVIG + steroids ± platelets
Paediatric cases	Observation or IVIG/steroids if bleeding

Prognosis & Follow-up

Aspect	Details
Prognosis – Children	Excellent; most resolve spontaneously
Prognosis – Adults	Chronic course common but manageable
Follow-up needed	Platelets, bleeding symptoms, treatment side effects
Post-splenectomy	Vaccines, sepsis prevention