Thrombotic thrombocytopenic purpura (TTP) and immune thrombocytopenic purpura (ITP): how are they treated?

Thrombotic thrombocytopenic purpura (TTP) and immune thrombocytopenic purpura (ITP) are two bleeding disorders characterized by abnormally low platelet counts. 

TTP is a serious disease leading to the formation of small clots that can obstruct the blood vessels, impairing oxygenation of the body's vital organs. TTP is characterized by purpura, anemia and possible renal failure. There are two forms of TTP: the acquired form, which is acquired during life as a result of an infection, an autoimmune disease or immunosuppression, for example, and the inherited form, which is due to the transmission of a genetic defect in the ADAMTS13 protein. In both cases, the symptoms are the same but the circumstances and age of onset vary.

ITP is a blood disorder in which there is an outbreak of platelet-destroying autoantibodies leading mainly to purpura, petechie, bleeding symptoms, anemia and fatigue. Many patients have few or no symptoms, but severe and life-threatening bleeding may occur. The reason for the formation of antibodies is unknown. However, in children, ITP often occurs after a viral infection. In children, the disease is cured in 60-70% of cases within a few weeks or months. On the other hand, in adults, it becomes chronic, i.e. lasting beyond 12 months, in 2/3 of all cases.

In the face of the symptoms, when either TTP or ITP is suspected, treatment is started immediately to ensure the patient's safety.

What are the possible treatments?

In both TTP and ITP, the first goal of any treatment is to raise the platelet count to a normal level (150,000 and 300,000/mm3). Platelets are vital components of the blood and very low levels can be fatal. Secondly, the treatment aims to improve the symptoms of the disease. 

What medications are recommended for treating immune thrombocytopenic purpura (ITP)? 

According to recommendations, ITP should be treated with corticosteroids such as prednisolone, in order to increase the platelet count. Once the platelet count has returned to a normal level, they can be discontinued gradually, under the supervision of a doctor. Steroids are not recommended for long-term use because of their serious side effects such as hyperglycemia and osteoporosis. Then, immunoglobulins can be prescribed as a second-line treatment. As their effect is immediate, they are prescribed in case of hemorrhage or when there is a need to rapidly increase platelet levels, for example before surgery. Drugs that stimulate platelet production, such as romiplostim and eltrombopag are commonly prescribed. These are analogues of thrombopoietin, a hormone produced by the liver and kidneys that regulates platelet production by the bone marrow.

Immunosuppressants, such as rituximab, are also recommended. Rituximab works by an immune suppression mechanism, inhibiting the antibodies that attack the platelets. However, due to immunosuppressive mechanism of action of this medication, the patient may become prone to infections. More rarely, removal of the spleen may also be an option. The spleen is the main organ where the antibodies that destroy platelets are produced, and it is also the main organ where a certain type of cells, called macrophages, that destroy platelets, are located.

What medications are recommended for treating thrombotic thrombocytopenic purpura (TTP)?

For TTP, the first-line treatment is: plasma infusions for hereditary TTP, and plasmapheresis (plasma exchange) for acquired TTP. The latter is used to remove antibodies that inhibit the ADAMTS13 enzyme responsible for regulating platelet aggregation and reintroduce plasma containing a functional enzyme. In many cases, plasmapheresis, or plasma exchange, is used to remove antibodies that inhibit the ADAMTS13 protease and to reintroduce a functional ADAMTS13 protein. There is also a routine prescription of corticosteroids for these patients in order to increase platelet levels and inhibit antibody formation. Rituximab is also prescribed for acquired TTP to inhibit the production of antibodies to the ADAMTS13 protease. Caplacizumab, recently approved for the treatment of TTP, acts by inhibiting platelet aggregation. More rarely, splenectomy can also considered an option for treating acquired TTP. Other symptomatic and supportive treatments may be considered as well.

With current standard treatments and rapid diagnosis, prognosis for patients is excellent. However, in many cases, patients may experience relapses and complications, especially in the case of TTP. They may also experience neurological disorders affecting their quality of life. Work is currently underway at international level to better understand the mechanisms and causes for resistance to the various treatments currently available, in order to develop new molecules and therapies.