Development of chronic disease in newly diagnosed Idiopathic Thrombocytopenic Purpura of Childhood. A randomized controlled study on the influence of treatment with intravenous gammaglobulin on the course of the disease.

Acute idiopathic thrombocytopenic Purpura (ITP) in childhood is characterized
by auto-immune destruction of platelets and a typical history of acute
development of purpura and bruising in an otherwise healthy child. The
incidence is about 5 in 100,000 children per year.
Management of acute ITP consists of carefull observation. Only in case of
severe bleeding treatment with corticosteroids or intravenous immunoglobulin
has to be instituted. The advantage of IVIG over steroids is the lack of
influence on diagnostic procedures in case of a wrong diagnosis, especially if
malignancy is the cause of thrombocytopenia.
Most children with newly diagnosed ITP will not suffer from serious bleedings
and will recover within 6 months. Nevertheless, thrombocytopenia has a major
influence on daily life activities, because all activities which have a risk of
causing severe bleeding have to be avoided. A group of about 25% of the
patients will remain thrombocytopenic after 6 months and thus are diagnosed
with chronic ITP. Incidence of bleeding correlates well with the duration of
the thrombocytopenia and thus with chronic disease.
In a previous prospective observational study we found a significant reduction
of relative risk of developing chronic disease in children treated with IVIG in
the acute phase. These results are confirmed by data of the international ITP
registry, a recent meta-analysis and research in mice.

To test the hypothesis that IVIG treatment diminish the risk of development of
chronic disease, we designed a prospective clinical intervention study in
children with newly diagnosed ITP.

The study comprises a randomised intervention study in which patients with
newly diagnoses acute ITP will be randomised to receive standard treatment,
namely carefull observation without medication, or intervention with IVIG
treatment.

Patients in the intervention arm will receive IVIG 0.8 g/kg once, within three
days of diagnosis. In all patients clinical data and blood samples will be
collected at diagnosis, 1 and 4 weeks and 3, 6 and 12 months after diagnosis.
Questionnaires regarding quality of life will be obtained at the same
timepoints.

Patients in the intervention arm of the study will receive IVIG regardless of
bleeding tendency. They will need an intravenous canule. There is a small risk
of adverse reactions. The most important adverse reactions is an allergic
reaction. The involved pediatricians will get proper instructions to recognize
and treat these adverse reactions.
All parents and patients aged sveen years and older will be asked to fill out a
short questionaire regarding quality of life.
Frequention of taking history, physical examination and blood samples is not
different from regular management of acute ITP. The quantity of blood samples
is more than during regular treatment. However, this quantity is limited, so
adverse consequences for patients are not to be expected.
Because of the minimal risk of the research project and the limited burden for
patients and parents, we have judged that the benefits of the project outweigh
these risks. The benefits for patients in the intervention arm are: a temporary
increase of platelet counts and therefore a decreased risk of severe bleeding.
For patients in the control arm there will be extra attention for quality of
life aspects.
If patients do not develop chronic ITP, benefits are evident: no limits in
physical activities anymore and a strongly reduced risk of bleeding, which will
significantly improve quality of life in patients as well of parents.