Idiopathic Thrombocytopenic Purpura (ITP)

Idiopathic Thrombocytopenic Purpura (ITP) is the most common bleeding disorder of children where platelets are coated by a circulating antibody, developed against platelet glycoprotein antigens and eventually destroyed in the spleen.

Types

• Acute Idiopathic Thrombocytopenic Purpura (ITP)
• Chronic Idiopathic Thrombocytopenic Purpura (ITP) (persistent thrombocytopenia >12 months)

Aetio-Pathogenesis

The aetiopathogenesis of Idiopathic Thrombocytopenic Purpura is unknown. However, in about 50-60% cases, this platelet destruction may follow an episode of viral upper respiratory tract infection about 2-3 weeks prior to the bleeding episodes. The viruses commonly involved are Epstein Barr virus (EBV), Rubella, Varicella, Measles, Parvovirus B19 and Influenza. The viruses produce antiplatelet antibodies and these coats the circulating platelets and the coated platelets are finally destroyed and removed by the spleen.

Clinical manifestations

Sudden onset of mucocutaneous bleeding (distinguishable from coagulopathy) in a previously healthy child

• Skin: Petechiae, purpura, ecchymoses and easy bruising
• Mucosa: Bleeding from gum, nose, conjunctiva, menorrhagia
• Internal bleeding e.g. haematuria, haematemesis & melaena, haemoptysis and intracranial bleeding are uncommon but can occur in severe thrombocytopenia and may be fatal

Physical Examination

• Evidence of bleeding in
  • Skin e.g. petechiae purpura or ecchymosis
  • Mucosa e.g. nose. gum, oral cavity, conjunctiva

However, patients neither have significant pallor, hepatosplenomegaly, lymphadenopathy nor bony tenderness.

Differential Diagnosis

• Henoch Schonlein purpura
• Dengue haemorrhagic fever (DHF)
• Leukaemia
• Aplastic anaemia
• Meningococcal septicaemia

1. Skin rash of Henoch-Schonlein purpura

These rashes are characterized as palpable purpura that evolves from red to purple and then to rusty brown before they eventually fade. These are non-tender, do not blanch on pressure. Lesions usually involve buttock, lower extremities and the hands (waist down distribution).

{image source: Infokid}

2. Skin lesions of acute meningococcaemia

Lesions consist of tender pink macules. petechiae and purpura. These are most prominent on the extremities and may form areas of frank necrosis.

3. Skin lesions of Dengue fever

Transient macular rash in first 1-2 days, maculopapular. scarlet morbilliform, from day 3-5.

Acute Idiopathic Thrombocytopenic Purpura (ITP): Clinical severity

• Mild: Bruising and petechiae, occasional minor epistaxis, very little interference with daily living
• Moderate: More severe skin and mucosal lesions. more troublesome epistaxis and menorrhagia
• Severe: Bleeding episodes e.g. menorrhagia, epistaxis, melaena, requiring transfusion or hospitalization, Symptoms interfere seriously with the quality of life

Diagnosis

ITP is diagnosed by-

• Excluding other causes of thrombocytopenia.g.­ acute leukaemia, aplastic anaemia
• Analysing the clinical & laboratory data of the case

Investigations

• CBC&PBF
  • Haemoglobin: Usually normal unless massive haemorrhage
  • TC and DC of WBC: Usually normal
  • Platelet count: Low
  • PBF: RBC (normal), WBC (mature). No blast cells. Larger platelets may be seen
• Coagulation profile (usually not required):
  • Bleeding time (BT): Prolonged
  • Prothrombin time (PT): Normal
  • aPTT: Normal
• Bone marrow study: Generally, not required for patients with isolated thrombocytopenia, who fit the diagnostic criteria above, but indicated, when-
  • Patients fail to respond to the recommended therapy for ITP
  • Cell lines, other than platelets are affected
  • The steroid is planned to treat the case
  • Bone marrow study findings: Megakaryocytes an increased. Erythroid and myeloid cellularity, as well as myeloid erythroid ratio, are normal

Differences between acute ITP leukaemia and aplastic anaemia

A. Clinical

B. Laboratory

Treatment

Acute ITP is a self-limiting disease and > 80% of children require no therapy. Only-

• Counselling to parents & patients about the disease
• Close observation of the patients
• Avoidance of aspirin, NSAID and
• Restriction from physical contact activities is recommended.

However, when the platelet count falls <20,000/cmm, treatment is required to induce a rapid rise of platelets to the safe level. The following drugs are recommended in this situation-

• IVIG: The treatment of choice for severe, acute bleeding. Dose: 0.8-1.0 g/kg/day for 1-2 days. It induces a rapid rise of platelet count (>20 x 10⁹/L) in 95% of patients within 48 hours. IVIG blocks the Fe-receptors in macrophages and thereby prevent phagocytosis of antibody-coated platelets
• Prednisolone: Patients with clinically significant but non-life-threatening­ bleeding may benefit from this
  Dose: 1-4 mg/kg/day, continued for 2-3 weeks until platelet count is > 20 x 10⁹/L
• IV anti-D to Rh-positive patients: Single dose: 50-75 μg/kg, induces a rapid rise of platelet count >20 x 10⁹/L within 48-72 hours in 80-90% of patients. This
  the antibody binds to the D antigen on RBCs which then interferes with the removal of antibody-coated platelets in spleen, resulting in improvement in thrombocytopenia
• Other options-
  • Splenectomy: Reserved for refractory
    thrombocytopenia with life-threatening haemorrhage
  • Platelet transfusion: Usually not indicated in acute ITP, as the transfused platelets will be liable to be coated by the antiplatelet-antibo­dies and destroyed If it is life-saving, transfuse along with IVIG or steroid

Prognosis

About 80% of children with acute ITP will achieve remission and 20% may turn into chronic ITP. The predictors of chronicity are-

• Female gender
• Age > 10 years at presentation
• Insidious onset of bruising
• Presence of other autoantibodies