Immune thrombocytopenia

Immune thrombocytopenia, previously known as Idiopathic thrombocytopenic purpura (ITP), is an autoantibody-mediated disease characterised by isolated thrombocytopenia with normal bone marrow.

Introduction

Immune thrombocytopenic purpura or ITP is an autoimmune condition in which the body produces antibodies against its own thrombocytes or platelets, which are destroyed. And this result in purpura, or small bleeding spots beneath the skin.

• M/C bleeding disorder presenting in children

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Types

• Acute ITP (Children, 60-75%)
  • < 6 months
• Chronic ITP (Adults)
  • > 6 months 

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Etiology

Primary cause:

• Idiopathic thrombocytopenic purpura (ITP)

Secondary causes:

• Autoimmune diseases
• Viral infection
• Malignancy
• Drug reaction

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Pathophysiology

Th1-dominant pro-inflammatory cytokine state
↓
Anti GpIIb/IIIa antibodies
(On platelet surface)
↓
Platelets trapped in the spleen
↓
Removed by splenic macrophages

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Clinical features

Symptoms and signs depend on the platelet count

• Afebrile presentation
• Sudden appearance of:
  • Bruises and mucosal bleeding
  • Epistaxis
  • Oral oozing
  • Prolonged bleeds with superficial trauma
• Examination:
  • Petechiae
  • Ecchymoses

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Diagnosis

• ↑ Bleeding time (BT)
• Rule out hepatitis, occult malignancy, hemolysis and hemolytic uremic syndrome:
  • Liver & renal function tests
  • Lactate dehydrogenase levels
• ↓ Platelet count

Peripheral blood smear:

• Abnormal cells (such as blasts) or malarial parasites
• Platelets:
  • Larger in size, indicating increased production
  • Exclude spurious thrombocytopenia

Screening tests (if sepsis is suspected):

• Disseminated intravascular coagulopathy (DIC)

Bone marrow biopsy:

In patients > 60 and refractory cases, or doubtful diagnosis

• ↑ Megakaryocytes
  • Hallmark of immune-mediated platelet destruction
• Rules out marrow infiltration, leukemia or bone marrow failure

Differential diagnosis:

Parameters	TTP-HUS	ITP	DIC
Platelets	↓	↓↓	↓
Haemoglobin	↓	Normal	↓
MAHA	Yes	No	Yes
Haemolysis	Abnormal	Normal	Abnormal
Peripheral smear	Schistocytes	Large platelets	Schistocytes
Creatinine	Normal/↑	Normal	Normal/↑
PT/INR/PTT	Normal	Normal	↑
Fibrinogen	Normal	Normal	↓
D-Dimer	Normal/↑	Normal	↑

*Microangiopathic hemolytic anemia (MAHA)

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Management

• Mild cases:
  • Close observation
• Haematological malignancy has been ruled out on bone marrow examination:
  • Corticosteroids:
    • Prednisone (1-4 mg/kg/ day for 2-4 weeks and then tapered)
    • Dexamethasone (20 mg/m²  over 4 days every 3 weeks for 4-6 courses)
• Serious haemorrhage:
  • Platelet transfusions + steroids
• Active bleeding:
  • Intravenous immunoglobulin (IVIg) (1 g/kg/day for 1-2 days)
• Rh-positive individuals:
  • Anti-D immunoglobulin (50-75 mg/kg)
• Rituximab

Refractory ITP:

• Combinations of the following:
  • Splenectomy
  • Danazol
  • Vincristine
  • Cyclosporine
  • Azathioprine
  • Rituximab (anti-CD20 monoclonal antibody)
  • Thrombopoietin receptor-binding agents