Immunothrombocytopenia (ITP, Werlhof disease)

In immunothrombocytopenia, the body mistakenly attacks its own platelets so that they break down more quickly. The possible consequence is bleeding. More about symptoms, diagnosis and therapy

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Immunothrombocytopenia (ITP) - a brief explanation

In immunothrombocytopenia (also called ITP or Werlhof disease), the body mistakenly attacks its own blood platelets (thrombocytes) with autoantibodies. In about 80 percent of the cases, there is no triggering cause, one then speaks of a primary form. In around 20 percent of cases, there is a trigger, such as a viral infection or medication, which is then referred to as a secondary form. Both forms of ITP lead to a lack of platelets, which leads to an increased tendency to bleed. Punctiform skin hemorrhages (petechiae) are typical. If there is a severe shortage of platelets, there is a risk of severe bleeding. The course of an ITP is different. It can appear acutely and stop by itself, or it can change into a chronic form. The therapy depends on the severity of the course and ranges from "waiting", the administration of medication (cortisone, stimulation of platelet formation by so-called thrombopoietin agonists) to removal of the spleen and must always be decided individually.

What is immunothrombocytopenia (Werlhof disease)?

Werlhof's disease (Werlhof's disease) - also known as immunothrombocytopenia or ITP for short - is an autoimmune disease in which those affected form antibodies against the body's own blood platelets (thrombocytes). The platelets loaded with antibodies are broken down very quickly in the spleen. As the platelet concentration in the blood decreases, the bleeding tendency increases. Those affected belong in the hands of specialists in the field of hematology.

ITP is a rare disease and can occur in both adulthood and childhood. In childhood ITP, boys are more often affected than girls, and it also seems to be more frequently associated with previous infections. The course of ITP in children is less often chronic (20 to 30 percent), in the affected adults the ITP is chronic in about 60 percent of the cases.

The mean age of onset of adult ITP is 50 to 55 years, but there seems to be a trend towards a higher age.

Background information - thrombocytes (blood platelets)

The platelets are made in the bone marrow and from there enter the bloodstream as soon as they are ripe. Their lifespan is eight to twelve days, after which they are broken down in the spleen. One of the main functions of platelets is to stop bleeding. In the event of vascular damage, the platelets attach to the vascular wall, seal it and set "repair mechanisms" in motion so that the bleeding stops and the vessel heals again.

In ITP, our immune system considers the surface structures of our own platelets to be "foreign", usually for no reason, so that they are broken down prematurely. Therefore, there is a shortage of platelets with the consequence of an increased tendency to bleed.

Cause: what causes immunothrombocytopenia (ITP)?

ITP is caused by a dysregulation of the immune system. Usually the trigger for this dysregulation remains unknown (80 percent of the cases), one then speaks of primary ITP. In so-called secondary ITP (20 percent of cases), a trigger can be found, for example after an infection or medication.

In childhood, ITP is more likely to occur after an infection and heals up after a few weeks. Even adults can heal spontaneously in the first year. After the 12th month of the disease, immune thrombocytopenia is considered chronic.

Causes of ITP

A reduction in platelets occurs in ITP due to an increased breakdown of blood platelets, for example through

  • Autoimmune diseases - this is where your own immune system is directed against the platelets
  • drug-induced, ultimately misdirected immune reaction
  • Viral infections such as HIV (human immunodeficiency virus) or hepatitis
  • after vaccinations

There are also many other diseases that lead to a reduced number of platelets in the blood. These fall under the term thrombocytopenia. Often, the blood formation is suppressed by chemotherapy or metastases in the bone marrow. ITP is, so to speak, a "subgroup" of thrombocytopenias.

Pathways of the immune response:

Platelet antibodies

The cause of thrombocytopenia (lack of blood platelets) is the formation of defense substances (antibodies) by the own immune system. These antibodies bind to their own platelets and thus lead to an increased breakdown of blood platelets in the spleen and liver. These autoantibodies (antibodies directed against the body's own components) not only lead to a faster breakdown of the platelets, but can also destroy the platelets themselves.

Dysregulation of the T cells

In ITP patients there is an imbalance between so-called regulatory and activating white blood cells. The T-lymphocytes seem to attack the blood platelets themselves and contribute to their destruction.

One speaks of ITP when the platelet count is repeatedly below 100 x 109 / L and other causes are excluded. The usual lower normal range limit for the platelet count in most laboratories is around 150 x109 / L.

Symptoms: what symptoms does immunothrombocytopenia cause?

When the number of blood platelets drops sharply, small injuries to the blood vessels can no longer be closed. Blood leaks from the blood vessels. The symptoms are correspondingly diverse. In the initial phase, small punctiform "flea-like" bleeding (petechiae) are typical, mostly on the skin and mucous membranes. The bleeding is the size of the head of a pin and is mainly found on the legs, less often on the trunk or arms. Bleeding can also occur in the area of ​​the mucous membranes of the mouth and nose. Due to the increased tendency to bleed, those affected develop bruises even with minor trauma. Urogenital bleeding (blood in the urine), increased menstrual bleeding or blood in the stool may also occur.

Very heavy bleeding can lead to acutely life-threatening shock symptoms and damage the affected organs (spleen, liver, kidneys and lungs, brain). This so-called "internal bleeding" rarely occurs in ITP.

In addition to the increased tendency to bleed, those affected can also experience exhaustion, tiredness and depressive moods.

Diagnosis: how is immunothrombocytopenia diagnosed?

ITP is a diagnosis of exclusion. This means that if the doctor suspects thrombocytopenia (reduction in the number of platelets in the blood), all other diseases that could also cause thrombocytopenia must first be ruled out. There is no laboratory test or investigation that an ITP can "prove".

Medical history and physical examination

First, attention is paid to typical symptoms, such as an increased tendency to bleed. In the conversation it is clarified whether other causes, for example the use of anti-coagulant medication, can explain the bleeding tendency.

Laboratory tests

The number of platelets in the blood count is markedly reduced. It must be ensured that the reduced platelet count did not first develop in the blood collection tube (so-called pseudothrombopenia). A blood smear will be examined by an experienced haematologist to rule out other blood disorders. The coagulation parameters are also determined.

Detection of platelet antibodies

The detection of platelet antibodies is not part of the standard diagnosis and is currently only recommended in a special laboratory in the case of chronic or atypical disease. False positive results are often found, which means that even in healthy people, antibodies bind to the platelet surface, but do not destroy them.

Bone marrow examination

If there are abnormal findings or if you are over 60 years of age, an examination of the bone marrow using a bone marrow aspiration is recommended in order to rule out other diseases (e.g. stem cell disease of the bone marrow).

Further possible investigations

Additional examinations can be useful. If bleeding in the lower bowel is suspected, the stool can be tested for blood (occult blood test). If bleeding in the stomach or esophagus is suspected, a gastroscopy can be performed. If internal bleeding is suspected, an ultrasound examination (sonography), computed tomography (CT) or magnetic resonance tomography (MRI) examination may be necessary.

Therapy: how is immunothrombocytopenia treated?

The therapy depends strongly on the individual case and the time of diagnosis. In addition, special point systems (scores) are used to recommend therapy. The decisive factors here are the severity of the bleeding tendency and the general condition of the person affected. Most children and adolescents with ITP only bleed lightly and the number of platelets usually normalizes on its own within six months, so that no therapy is necessary.

Treatment of acute ITP

In the acute form, the focus is on preventing or stopping bleeding. In so-called first-line therapy, if there is only a slight tendency to bleed and depending on the number of platelets, you can watch-and-wait or the doctor prescribes corticosteroids for at least three weeks should be taken (in adults). Certain protocols are available for the doctor for this purpose. First-line therapy is usually over after about three months. With cortisone therapy, there is an increase in platelets in 90 percent of those treated, which, however, decrease again in the majority of those affected after discontinuing therapy. This indicates that corticosterioids can lessen the severity of the course, but not speed healing.

Many patients undergoing cortisone therapy also experience side effects such as weight gain, acne or osteoporosis, so that the administration of cortisone should be limited in time. Especially in children, cortisone therapy can be dispensed with in mild forms. If the focus is on severe or life-threatening bleeding, this is a clear indication for treatment. Steroids, immunoglobulins via the vein (IV) or special oncological / immunological drugs used in cancer therapy are used. It may be necessary to administer platelet concentrates, TRAs (thrombopoietin receptor agonists) or even to remove the spleen (splenectomy).

Treatment of Chronic ITP

For chronic ITP with persistent or recurrent heavy bleeding, treatment with TRAs (thrombopoietin receptor agonists) or removal of the spleen (spenectomy) may be considered. However, since the TRAs were approved (see below), removal of the spleen is much less necessary. The attending physician, together with the patient and their relatives, will carefully weigh the possible benefits against the risks of the operation before the operation. The possible "cure" with the prospect of a life without the side effects of drug therapies and without the risk of dying from the consequences of severe bleeding are offset by possible complications from the operation. In about every third patient, at least one relapse requiring treatment occurs despite the removal of the spleen. The risk of death from the operation is one percent.

What are TRAs (Thrombopoietin Receptor Agonists)?

So-called TRAs (Eltrombopag and Romiplostim) are used to treat chronic ITP. By binding to the throbopoeitin receptor, the drugs cause an increase and further development of megakaryocytes, which develop into platelets. This leads to an increase in the platelet count.

Eltrombopag is taken orally as a tablet once a day.

Romiplostim is injected into the subcutaneous fat tissue (subcutaneously) once a week.

TRAs are usually well tolerated, possible side effects can be headache, tiredness, nosebleeds, joint and limb pain, diarrhea and increased infections of the upper respiratory tract. If the response to one of the drugs is too low, you can switch to the other.

ITP in adulthood often differs in its course and prognosis compared to ITP in children. Children and adolescents should be cared for by a specialized treatment team (Clinic for Pediatric Hematology).

Prof. Dr. Michael Spannagl

© Thomas Corner / Berlin

Our advisory expert:

Professor Dr. Michael Spannagl works as a hemostaseologist at the Ludwig Maximilian University (LMU) in Munich and is very well known in specialist circles for his work in the field of hemostasis, intensive therapy and laboratory medicine. He is responsible for experimental and clinical studies on anticoagulation, therapy of hemophilia and management of blood components. He is a member of several committees (DIN, ISO, CEN) for the development of standards for medical laboratory diagnostics and for quality management. He was guideline coordinator and deputy chairman of the Society for Thrombosis and Haemostasis Research (GTH) and is chairman of the board of the Society for the Promotion of Quality Assurance in Medical Laboratories (INSTAND e.V.) and a member of the Blood Working Group of the Federal Ministry of Health (BMG). He is the author and co-author of over 250 publications (articles and book chapters). As a member of the commission of the German Medical Association, he co-authored the guidelines on "Therapy with blood components and plasma derivatives" and the guidelines on "Prophylaxis and therapy of venous thromboembolism (VTE)". In addition, Prof. Spannagl is an active member of numerous national and international scientific societies for hemostasis, transplant and laboratory medicine as well as for standardization and quality management in medical laboratories.

Swell:

  • Onkopedia, Immunothrombocytopenia (ITP). Online: https://www.onkopedia.com/de/onkopedia/guidelines/immunthrombozytopenie-itp/@@guideline/html/index.html (accessed on February 27, 2020)
  • Children's blood diseases, immunothrombocytopenia (ITP). Online: https://www.kinderblutkrankheiten.de/content/ Krankungen/blutplaettchen/immunthrombozytopenie_itp/ (accessed on February 28, 2020)
  • Priv.-Doz. Dr. med. Oliver Meyer, Charité - Universitätsmedizin Berlin, Institute for Transfusion Medicine. Diagnosis and therapy of immune thrombocytopenia (ITP). Online: https://cme.medlearning.de/novartisoncology/itp_diagnostik_therapie/pdf/cme.pdf (accessed April 20, 2020)

Important NOTE:
This article contains general information only and should not be used for self-diagnosis or self-treatment. He can not substitute a visit at the doctor. Unfortunately, our experts cannot answer individual questions.

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