Towards a more effective and efficient use of intravenous immunoglobulin in children with immune thrombocytopenia LSBR 1546
Project leader: Prof. Dr. Masja de Haas (Sanquin Research and Leiden University Medical Center)
PhD student: David Schmidt (August 2016 – August 2020)
PhD student: Anne Tess Jolink (August 2021 – November 2022)
In children, skin bleeding may be the first indication that the patient suffers from immune thrombocytopenia (ITP). In this autoimmune disease, the own immune system attacks proteins which are located on platelets. Subsequently, the platelets get damaged, resulting in a shortage of platelets in the blood; so called thrombocytopenia. This can cause an increased bleeding tendency with frequent skin bleeding, which ranges from small point hemorrhages to large bruises. Sometimes severe bleeding can occur, with mucosal hemorrhages, but there is also a danger of a brain hemorrhage. In childhood ITP, there is often an episode with an infection or vaccination prior to the occurrence of ITP, but not always. There is no diagnostic test for ITP, and it is not clear whether all children diagnosed with ITP exhibit the same underlying mechanism of platelet destruction. In childhood, ITP is often a temporary problem that the body solves itself (transient ITP). However, in some children there is long-term or even permanent thrombocytopenia (persistent and chronic ITP). Treatment of ITP by immunomodulatory drugs such as corticosteroids or intravenous immunoglobulins (IVIg) may advance the recovery from thrombocytopenia and thus prevent bleeding symptoms. Unfortunately, this treatment only works in some of the patients
The aim of this research project was to better understand and predict whether spontaneous recovery or a positive treatment effect of IVIg can be expected in a child with ITP.
For this purpose, molecular disease mechanisms have been mapped and linked to clinical data. As the age of children increases, there is a higher risk of persistent/chronic ITP. At the same time, most children with persistent/chronic ITP are of a young age (under 5 years), because ITP is relatively more common in this group. This makes it difficult for the attending physician to use the age of a child for prediction of the course of the disease. We therefore investigated the diagnostic and prognostic value of detection of platelet antibodies. We found that the presence of platelet antibodies is specific to ITP and highly correlated with a transient course of disease.
As part of our research we have developed a new clinical prediction score; the Childhood ITP Recovery Score. We have shown that this score can be improved by the addition of biomarkers. If ITP is presumed, such scores can be used in communication with the child and parents about the expected prognosis and for treatment decisions and use of intravenous immunoglobulin. The scores can also be used to decide on early comprehensive diagnosis of other causes of thrombocytopenia and bleeding (such as genetic testing).
In summary, we have taken the first steps to achieve personalized care for children with the rare disease ITP.