Immune thrombocytopenia (ITP) describes an autoimmune disorder in which the number of circulating platelets is reduced. This is due to their increased destruction, and sometimes also due to reduced production. ITP was previously known as idiopathic thrombocytopenic purpura but this is outdated, now that it is known to have an autoimmune cause.

Primary vs secondary ITP

Primary immune thrombocytopenia (ITP) is a haematological disorder characterised by isolated thrombocytopenia (platelet count <100 × 10⁹/L) in the absence of an identifiable cause. The thrombocytopenia is secondary to an autoimmune phenomenon and involves antibody destruction of peripheral platelets. Risk factors are women of childbearing age, and males and females <10 or >65 years old.

Secondary ITP includes all forms of ITP where associated medical conditions or precipitants can be identified. The distinction between primary and secondary ITP is clinically relevant because of their different natural histories and distinct treatments, including the need to treat the underlying condition in secondary ITP.

Causes of secondary ITP include:

• HIV
• Hepatitis C
• Helicobacter pylori
• Immunodeficiencies
• Immunological/autoimmune disorders (e.g. systemic lupus erythematosus, Evans' syndrome, antiphospholipid syndrome, and autoimmune thyroid disease)
• Lymphoproliferative disorders
• Drug-induced
• Vaccine exposure (very rare)

Clinical features

ITP is a diagnosis of exclusion, so the history, examination, and tests are directed at ruling out other potential causes of a low platelet count.

Patients may present with bleeding (e.g. bruising, petechiae, haemorrhagic bullae, bleeding gums). Fatigue is also commonly reported, and there may be a preceding viral illness (particularly in children), but otherwise the patient usually feels well. Some patients present with no signs or symptoms. In about half of adult cases, thrombocytopenia is an incidental finding on routine full blood count (FBC) or during investigation for another illness.

Physical examination is often normal except for possible bruising, petechiae, or bleeding related to thrombocytopenia. Specifically, there should be no lymphadenopathy or hepatosplenomegaly.

Investigations

• Full blood count and peripheral blood smear
  • Reveals isolated thrombocytopenia (platelet count <100 × 10⁹/L) without other abnormalities.
• Bone marrow biopsy and/or aspirate
  • Only considered if atypical blood film features are present.
  • Can also be considered in patients who are unresponsive to medical therapy, or prior to splenectomy
• Investigations to exclude secondary causes e.g. HIV, hepatitis and Helicobacter testing, thyroid function tests, immunoglobulins, pregnancy test

Management

Different treatment modalities and goals should be considered for the different phases of ITP.

• Treatment in newly diagnosed patients
  • The treatment goal is to rapidly obtain a safe platelet count to prevent or stop haemorrhages, and to ensure an acceptable quality of life with minimal treatment-related toxicities.
  • Generally asymptomatic patients do not require immediate treatment; observation is advised.
  • A platelet count of 20-30 × 10⁹/L is generally chosen as a threshold for treatment due to the increased risk of bleeding once platelet count reaches this level. A corticosteroid, IVIG, and anti-D immunoglobulin are considered first-line treatments.
  • Ultimately, the decision to treat should be individualised, taking into account factors such as severity of bleeding symptoms, risk of bleeding, risk of side effects from treatment, lifestyle (e.g. being employed in a high-injury risk profession or participating in high-injury risk activities), and patient preference.
• Emergency treatment
  • All patients (children or adult) with life- or organ-threatening bleeding, regardless of platelet count, require emergency treatment comprising a combined therapeutic approach with platelet transfusion, a corticosteroid (e.g. prednisolone, methylprednisolone, or dexamethasone), and intravenous immunoglobulin (IVIG). Emergency treatment may take 1-5 days to have an effect, and usually lasts for 2-4 weeks, whether or not the patient has had a prior splenectomy.
  • Although platelets are likely to be rapidly destroyed during transfusion, there is evidence to suggest that patients with active bleeding respond transiently to transfusion. IVIG can prolong platelet survival; therefore, platelet transfusion may be more effective if given after IVIG infusion.
  • The antifibrinolytic agents aminocaproic acid and tranexamic acid can help stabilise clots that have already formed. These agents can be used as adjunctive treatment as they do not affect platelet count. However, they are contraindicated in patients with haematuria as clots in the collecting system of the kidneys can lead to outlet obstruction.
• Treatment in patients with persistent or chronic disease
  • Patients who continue to have ITP during the 3-12 month period after diagnosis (e.g. due to lack of spontaneous remission, or intolerance or failure of first-line treatments) are defined as having persistent disease; if ITP continues beyond 12 months, patients are defined as having chronic disease.
  • Some patients with persistent or chronic disease respond to first-line treatments, but require continuous treatment to achieve a platelet count that is safe. Patients with persistent or chronic disease who are intolerant of, or have failed, first-line treatments may require second-line treatment to control bleeding or to reduce the risk of bleeding.
  • Second-line treatments include mycophenolate, thrombopoietin receptor agonists, rituximab or fostamatinib. In cases of treatment failure or intolerance with one second-line drug, switching to another second-line drug or splenectomy may be considered.