Introduction
Platelets are small cells derived from bone marrow cells called megakaryocytes. The main function of platelets is to stop bleeding after cuts or trauma such as injury, surgery, or dentistry. Thrombocytopenia is the term used when platelets are below normal numbers (150–400 × 109/l). Immune thrombocytopenia (ITP) is one type of thrombocytopenia where the patient's immune system removes platelets or interferes with their production in the bone marrow.
Causes
There are many causes of thrombocytopenia including vitamin deficiencies, infection, drugs, bone marrow infiltration, and autoimmune disease such as ITP. ITP used to be called idiopathic thrombocytopenic purpura because the underlying cause of the low platelet count is unknown. The disease has been renamed immune thrombocytopenia because the underlying process is driven by the immune system and purpura is often absent.
Research has shown that in most cases the ITP is due to a self-reacting autoantibody (i.e. self-reacting antibody) which is binding to the patient's platelets causing them to be removed by the spleen. Recent research has shown that the underlying mechanism in ITP is much more complex than previously believed and include: autoantibody binding to megakaryocytes preventing platelet release, or causing premature death of the megakaryocytes. In addition, T cells appear to play a role in some types of ITP. The different underlying mechanisms for ITP probably explain why patients behave differently to the treatments used.
Symptoms and signs
Most patients with ITP have few major problems. In fact, for most people, ITP is a minor disorder. If the platelet count is in the range 50–100 × 109/l there is usually no bleeding or bruising. If the platelet count drops to less than 50 × 109/l there may be bruising, and when the platelet count drops to less than 20 ×109/l, purpura and petechiae may develop (these are pinpoint blood spots under the skin). Sometimes patients have bleeding from mucous membranes such as the nose, the gums, and female patients may suffer with heavy periods ().
Figure 1. Severe elbow bruising following minor trauma in a 22-year-old female patient who has platelets <10 × 109/l.
The most serious bleeding tends to occur in patients whose platelet count is less than 10 × 109/l. However, most patients with platelets less than 10 × 109/l have no major bleeding problems. So the chances of you suffering serious hemorrhage are very low.
Tests
Investigation focuses on detecting underlying causes for the thrombocytopenia and for this reason the diagnosis of ITP is one of exclusion. In the majority of cases no cause is found. Investigations used are mainly blood tests but in some cases (e.g. an older patient, or one in whom there are atypical features) a bone marrow examination may be carried out.
| •. | Full blood count/complete blood count | ||||
| •. | Kidney and liver function | ||||
| •. | Autoantibody screen | ||||
| •. | Tests for hepatitis viruses A, B, C and HIV | ||||
| •. | Vitamin levels e.g. vitamin B12 and folate | ||||
| •. | Immunoglobulin levels | ||||
| •. | Blood group | ||||
| •. | Helicobacter pylori test. | ||||
Treatment options
The aim of treatment is to maximize patient safety. Our management of ITP today is less aggressive than previously and we prefer not to treat patients with drugs. If we feel the platelet count is reasonable without any medication then we would prefer to leave patients off treatment. We only treat patients who are at high risk of bleeding or who face some kind of challenge such as surgery or dentistry.
Drug treatments
Generally, if the platelet count is less than 10 or 20 ×109/l first-line treatment will be started. Corticosteroids or intravenous immunoglobulin (IVIg) will be used. If the platelets drop we tend to use a second-line drug such as an immunosuppressant to reduce the level of autoantibody. If the second-line treatment fails rituximab or possibly one of the new thrombopoietic agents romiplostim or eltrombopag are introduced.
Surgical treatment
Splenectomy has been used as a treatment for ITP. Two-thirds of patients respond to this treatment after which they require no ITP medications. However, the popularity of splenectomy is declining partly because it is an invasive procedure and also because of the realization that patients can manage quite adequately with much lower platelet counts than previously thought.
Short-term treatment
Many patients have platelet counts that are safe for day-to-day living, e.g. ∼30 × 109/l but there may be occasions where a higher count is required, e.g. prior to surgery, dentistry, or other challenge likely to cause bleeding. In these cases the patient will be given a short-term treatment which will bring the platelets up for two or more weeks making it safe for the patient to have surgery, and also prevent bleeding in the post-operative period after which time the treatment may be tapered off.
ITP in pregnancy
ITP may present in pregnancy and, because ITP is often caused by an antibody against the patient's own platelets, the antibody can cross the placenta and affect the baby's platelets. Managing a woman with ITP who is pregnant involves patients having to attend the hospital more often than a ‘standard’ pregnant patient, to check the full blood count and monitor the pregnancy. Quite often we have to use IVIg or steroids during the pregnancy to bring the platelet count up to 20 × 109/l or more through pregnancy (this is considered a safe count in pregnancy). At the time of delivery the platelets need to be 50 ×109/l or greater, and if epidural anesthesia is planned, the platelet count should be at least 75–80 × 109/l. The baby's platelets are checked at birth and for a few days after birth to make sure the platelet count is adequate.
Outlook
For most patients, ITP is a minor disorder which simply requires periodic complete blood counts. If platelets drop dramatically, or there is bleeding, we will intervene with some treatment. In general, we use treatments with as few side effects as possible since our aim is to keep patients safe, while enjoying a good quality of life:
| •. | For most patients ITP is a minor disorder | ||||
| •. | The cause is unknown but we do know that the patient's immune system removes platelets or prevents them from being produced in adequate numbers | ||||
| •. | Many patients can be managed by watching and waiting | ||||
| •. | If there is bleeding or the patient requires surgery then treatment may be offered. | ||||
Resources
There are many resources online but those that are most worth a visit are: the Platelet Disorder Support Association (http://www.pdsa.org), UK ITP Support Association (http://www.itpsupport.org.uk), and the UK Adult ITP Registry (http://www.ukitpregistry.com). The latest consensus on diagnosis and treatment can be found in the journal Blood, volume 14, pages 168–186 (2010).