What is chronic idiopathic thrombocytopenic purpura (ITP)?
Chronic idiopathic thrombocytopenic purpura (ITP) is a condition in which the body’s immune system destroys platelets (autoimmune), the cells responsible for blood clotting. This can lead to a low platelet count, also known as thrombocytopenia and bleeding.
The word “chronic” means that the condition lasts for more than six months. The word “idiopathic” means that the cause of the condition is unknown.
Is chronic idiopathic thrombocytopenic purpura (ITP) common?
Chronic idiopathic thrombocytopenic purpura is a relatively common disorder. In general, the incidence rate of chronic ITP is estimated to be around 2-3 new cases per 100,000 people per year. The highest incidence is found in women aged 15 – 50 years old. It is the most common cause of thrombocytopenia without anemia or neutropenia.
What are the clinical features of chronic idiopathic thrombocytopenic purpura (ITP)?
The clinical features of chronic idiopathic thrombocytopenic purpura (ITP) can vary depending on the severity of the condition and with a gradual onset.. Some people with chronic ITP may have no symptoms at all, while others may experience bleeding, bruising, or fatigue.
The most common symptom of chronic ITP is bleeding. This can include:
- Easy bruising
- Petechiae (small, red spots on the skin caused by bleeding)
- Purpura (larger areas of bleeding under the skin)
- Nosebleeds
- Gum bleeding
- Heavy menstrual bleeding
- Bleeding in the stool or urine
- Bleeding in the brain (rare)
Mucosal bleeding occurs in severe cases. Chronic ITP tends to relapse and remit spontaneously thus difficult to predict.
Other symptoms of chronic ITP may include:
- Fatigue
- Shortness of breath
- Pale skin
- Dizziness
- Headache
Chronic ITP can also cause complications, such as:
- Anemia (low red blood cell count)
- Splenomegaly (enlarged spleen)
- Infection
- Autoimmune disorders
How is chronic idiopathic thrombocytopenic purpura (ITP) an autoimmune disorder?
The mechanism of how ITP occurs is not well understood. However, it is believed to be an autoimmune disorder.
The thrombocytopenia is due to premature removal of platelets that are coated by allo/autoantibodies. These are detected by macrophage as foreign material. Hence there is removal of the platelet-Ab complex in the spleen.
The primary public antigen targeted for immune attack in ITP is GPIIb/IIIa which undergoes a conformational change during platelet activation and is the site of fibrogen cross-linking. This cross-linking event is the crucial step in platelet aggregation and the propagation of the primary platelet plug. Once the antibody-coated platelet is recognized and engulfed by the macrophage, GPIIb/IIIa as well as other platelet membrane proteins are degraded.
These peptide antigens are then coupled with HLA class 2 molecules and displayed on the macrophage cell surface. This antigen-presenting complex interacts with the T-cell receptor on CD4 helper lymphocytes, inducing proliferation and recruitment of antigen-specific B-cell clones which also proliferate and produce high levels of antibody against not only GPIIb/IIIa, but also GPIb/IX and other platelet antigens.
The rapid destruction of platelets by resident macrophages results in Tpo-mediated stimulation of megakaryocyte production in the bone marrow. Thus the marrow can have normal or increased megakaryocyte numbers. The normal lifespan of a platelet is 7 -10 days but in ITP this is reduced to a few hours.
What are the laboratory tests involved in diagnosing chronic idiopathic thrombocytopenic purpura (ITP)?
The laboratory investigations of chronic idiopathic thrombocytopenic purpura (ITP) are aimed at assessing the platelet count and other factors that may be contributing to the condition.
The most important laboratory investigation for chronic ITP is a complete blood count (CBC). A CBC measures the number of platelets and other types of blood cells in the blood. A low platelet count is the hallmark of chronic ITP (10 – 50 x 109/L).
Other laboratory investigations that may be ordered for chronic ITP include:
- Peripheral blood smear: A peripheral blood smear is a microscopic examination of blood cells. There will be thrombocytopenia with large platelets.
- Bone marrow biopsy: A bone marrow biopsy is a procedure in which a small sample of bone marrow is removed and examined under a microscope. This test can be used to assess the production of platelets and other blood cells.
- Direct antiglobulin test (DAT): The DAT is a test that is used to detect antibodies on the surface of red blood cells. A positive DAT may be seen in chronic ITP if the autoantibodies are also targeting red blood cells.
- Other autoimmune tests: Other autoimmune tests, such as an antinuclear antibody (ANA) test or a rheumatoid factor (RF) test, may be ordered to rule out other autoimmune disorders that may be associated with chronic ITP.
- Specific antiglycoprotein GPIIb/IIIa or GPIb antibodies on the platelet surface or in the serum of most chronic patients.
How are chronic idiopathic thrombocytopenic purpura (ITP) treated and managed?
The treatment and management of chronic idiopathic thrombocytopenic purpura (ITP) are aimed at preventing bleeding and improving the quality of life. The specific treatment approach will vary depending on the severity of the condition and the individual’s needs.
Observation
In some cases, chronic ITP may improve on its own without treatment. If platelet count is over 30 x 109/L no treatment is necessary unless the bleeding is severe, which involves regular monitoring of platelet count and symptoms. If the platelet count is stable and there are no bleeding symptoms, the doctor may recommend continuing observation. The treatment of chronic ITP aims to maintain a platelet count above 50 x 109/L to prevent spontaneous bruising or bleeding.
Medications
If the platelet count is low or experiencing bleeding symptoms, there are a number of medications that can be used to treat chronic ITP, including:
- Corticosteroids: Corticosteroids are medications that suppress the immune system. They are often the first line of treatment for chronic ITP.
- High-dose intravenous immunoglobulin therapy to produce a rapid rise in platelet count especially in patients with life-threatening haemorrhage or during pregnancy or prior to surgery
- Immunosuppressants: Immunosuppressants are medications that suppress the immune system. They are often used in combination with corticosteroids or other medications to treat chronic ITP.
- Thrombopoietin receptor agonists (TPO-RAs): TPO-RAs are medications that stimulate the production of platelets. They are often used to treat chronic ITP in adults.
Platelet transfusions
If the platelet count is very low or there is severe bleeding, the patient may need platelet transfusions. Platelet transfusions can help to increase the platelet count and reduce the risk of bleeding although their benefit will only last a few hours.
Splenectomy
The spleen is an organ that plays a role in the destruction of platelets. In some cases, removal of the spleen (splenectomy) may be recommended to treat chronic ITP. Splenectomy is often considered a last resort, as it is associated with some risks, such as an increased risk of infection.
Below is a synopsis of chronic ITP.
Definition
Thrombocytopenia due to immunologically-mediated increased destruction of platelets.
Predisposing factors
- Idiopathic (most common)
- Associated with SLE, HIV, CLL, Hodgkin disease or AIHA
Incidence rate
- Most common in adults (20 – 50 years old)
- Male: female = 1:3
Clinical features
- Gradual onset
- Mucocutaneous bleeding
- Menorrhagia
- Recurrent epistaxis
- Easy bruising (ecchymoses)
Pathophysiology
At the heart of ITP lies an autoimmune attack, where the body’s immune system mistakenly targets its own platelets. Antibodies, the body’s defense against foreign invaders, are produced and attach to the surface of platelets, marking them for destruction.
Laboratory investigations
Treatment and management
- If platelet count > 30,000/µl: no treatment
- Severe: prednisolone and/or IVIG or anti-D immunoglobulin
- Splenectomy
