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Immune Thrombocytopenic Purpura (ITP)

Immune Thrombocytopenic Purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is an autoimmune disorder characterised by a low platelet count in the absence of other causes. The condition often leads to an increased risk of bleeding from mucosal surfaces such as the nose or gums, or from the skin, resulting in purpura and bruises.

There are two primary forms: an acute form generally observed in children, often following a viral infection and typically resolving within two months, and a chronic form seen in adults, persisting for longer than six months without a specific identified cause.

Petechiae on the lower extremities
Petechiae on the lower extremities

Signs and Symptoms

ITP is marked by the spontaneous formation of bruises (purpura) and petechiae (tiny bruises), predominantly on the extremities. Bleeding from the nostrils and gums, as well as menorrhagia (excessive menstrual bleeding), can occur when the platelet count falls below 20,000 per μL. A platelet count below 10,000 per μL can lead to the spontaneous formation of haematomas in the mouth or on other mucous membranes.

In severe cases, platelet counts dropping to extremely low levels (<5,000 per μL) can result in serious complications such as subarachnoid or intracerebral haemorrhage, lower gastrointestinal bleeding, or other internal bleeding.

Oral petechiae/purpura - lower lip
Oral petechiae/purpura - lower lip
Petechia on the tongue in a person with platelets of 3 due to ITP
Petechia on the tongue in a person with platelets of 3 due to ITP

Pathogenesis

In around 60% of cases, antibodies against platelet surface antigens, primarily glycoproteins IIb-IIIa or Ib-IX, and of the immunoglobulin G (IgG) type, can be detected. These antibodies make platelets susceptible to opsonisation and phagocytosis by splenic macrophages and Kupffer cells in the liver. The immune mechanism involves the destruction of platelets and damage to megakaryocytes, the precursor cells to platelets.

Recent research indicates that impaired production of thrombopoietin, the hormone stimulating platelet production, may also contribute to the reduction in circulating platelets.

Diagnosis

The diagnosis of ITP is predominantly one of exclusion, requiring the elimination of other potential causes of thrombocytopenia. Initial tests include a complete blood count and examination of the blood film. Additional tests such as bone marrow biopsy may be necessary, especially in patients over 60 or those not responding to initial treatment. Tests for HIV and hepatitis C are also recommended as these infections can cause thrombocytopenia.

Blood film showing giant platelets in a person with ITP (Giemsa stain)
Blood film showing giant platelets in a person with ITP (Giemsa stain)

Treatment

Steroids

Initial treatment often involves corticosteroids to suppress the immune system. Doses and administration methods vary depending on platelet count and bleeding severity. Oral prednisone or prednisolone is commonly used, with intravenous options like dexamethasone or methylprednisolone reserved for urgent cases.

Anti-D

For Rh-positive patients with functional spleens, intravenous administration of Rho(D) immune globulin (Anti-D) may be used, though its exact mechanism is not fully understood.

Steroid-Sparing Agents

Immunosuppressants like mycophenolate mofetil and azathioprine are increasingly used for their effectiveness. In chronic refractory cases, vincristine may be attempted, though it comes with significant side effects.

Intravenous Immunoglobulin

Intravenous immunoglobulin (IVIg) can be effective in decreasing the rate of platelet destruction but is typically a short-term solution due to its high cost and transient effects.

Thrombopoietin Receptor Agonists

Agents like romiplostim and eltrombopag stimulate platelet production in the bone marrow and have shown success in treating refractory ITP. They come with side effects such as headache, joint pain, and an increased risk of blood clots.

Surgery

Splenectomy may be considered for patients unresponsive to steroid treatment or those with frequent relapses. The procedure reduces platelet destruction but carries risks, especially during surgery.

Platelet Transfusion

Platelet transfusions are generally reserved for emergencies as they do not provide a long-term solution.

H. pylori Eradication

In adults, particularly in areas with high prevalence of Helicobacter pylori, treating the infection can improve platelet counts in a third of patients.

Prognosis

Children often achieve remission, with most cases resolving within six months. In adults, ITP tends to be chronic, with a 20-40% chance of durable remission. The condition carries a higher mortality rate, particularly among the middle-aged and elderly.

Pregnancy

ITP can occur during any trimester of pregnancy and is the most common cause of significant thrombocytopenia in the second trimester. Pregnant women with ITP require careful management to mitigate risks to both the mother and the foetus, with treatments tailored to maintain safe platelet levels for delivery.

History

ITP was first reported in 1735 by the German physician Paul Gottlieb Werlhof. The condition was linked to platelet abnormalities in the 1880s, and the first successful therapy, splenectomy, was reported in 1916. The introduction of steroid therapy in the 1950s marked a significant advancement in treatment options.


Self-assessment MCQs (single best answer)

What is the primary characteristic of Immune Thrombocytopenic Purpura (ITP)?



What is a common initial symptom of ITP?



Which type of antibodies are typically involved in the pathogenesis of ITP?



What diagnostic test is primarily used to exclude other causes of thrombocytopenia in ITP?



Which treatment is often the first line of therapy for ITP?



What is the typical duration of the acute form of ITP in children?



Which hormone is involved in stimulating platelet production, potentially impaired in ITP?



What is the main complication of extremely low platelet counts (<5,000 per μL) in ITP?



Which surgical procedure may be considered for ITP patients unresponsive to other treatments?



In which trimester of pregnancy is ITP most commonly the cause of significant thrombocytopenia?



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