The sequestration pattern of thrombocytes in healthy adults: results of the ITP liver and spleen scan.

Splenectomy is a commonly used second line therapy for Immune Thrombocytopenia
(ITP). Several studies have shown that outcome of spleen-liver scans are
associated with treatment success after splenectomy. These spleen-liver scans
analyze the sequestration pattern of labeled thrombocytes. The limited evidence
available shows that a splenic sequestration pattern is associated with a high
rate of treatment success (88%), a mixed splenic/hepatic pattern with an
intermediate rate of treatment success (55%) and a hepatic pattern with a low
(16%) rate of treatment success after a splenectomy. The pathophysiology is
still unknown. Furthermore, these studies only investigated sequestration
patterns in patients with ITP. To the best of our knowledge, no studies on
platelet sequestration pattern has been conducted in healthy adults. To gain
insight in the mechanisms of platelet destruction and the pathophysiology of
treatment success it is important to compare healthy adults with ITP patients.
Until now, no studies have been performed concerning the pattern of platelet
destruction in healthy subjects and the role of the spleen and liver in this
process. Gaining insight into the platelet sequestration patterns in healthy
adults allows us to compare these results with those of ITP patients and be
able to classify the pattern as *normal* or *deviant*, which might give more
insight into platelet destruction characteristics of ITP patients. Moreover,
there are currently insufficient data available to evaluate whether these
platelet sequestration patterns could change over time spontaneously. This
information could shine a new light on the physiology of the lifespan of
platelets as well as the use of the ITP liver/ spleen scan as a diagnostic tool
in management of ITP.

The main objective of this study is to describe the sequestration pattern of
platelets in healthy adult volunteers. The secondary objective is to make a
comparison between the sequestration patterns in healthy volunteers, and the
patterns in ITP patients (as found in previous studies). Moreover, we aim to
compare the sequestration pattern of platelets in healthy adults between two
different time points.

This is a prospective cohort study. Ten healthy volunteers will be included in
this study. The Participants will undergo an ITP liver/spleen scan.
Participants have a follow-up of two months.A screening assessment will be
performed to asses the eligibilty of each volunteer for this study. Potential
study participants will be interviewed about their clinical history and a blood
sample will be taken. If a volunteer is included in the study, they will
undergo the ITP liver and spleen scan. The 111-indium scan will be performed at
the Haga Teaching Hospital in the Netherlands. Sixty-two ml whole blood will be
derived from the study participants (t= 0). In the lab of GE-Health the
platelets within this blood sample will be labelled with 111-indium tropolone.
Moreover, platelet counts will be determined. Three to four hours after the
blood samples are taken the platelets will be reinfused in the patient (t=1).
During the first 30 minutes after infusion, dynamic series (both anterior and
posterior) and static series will be made (t=2). At 3 hours (t=3), 24 hours
(t=4) and 48 hours (t=5) a static study will be made and blood samples of 10 ml
will be taken at each time point. Platelet counts (PC) are determined from
these blood samples. After two months, all study participants will be called
and asked some follow-up questions.

The procedure for the 2nd ITP liver spleen scan will be largely the same,
except for the following:
1) Four additional scans at t= 72 hr, t = 96 hr, t= 120 hr and t = 144 hr will
be performed. The scan at t =120 hr and t = 144 hr will take 5 minutes longer
than the other scans.
2) A total body scan will be made instead of a scan of only the abdomen.

Patients will again be screened for their eligibility (t=6). During the first
day of the ITP liver/ spleen scan blood samples will be taken, platelets will
be labelled with 111-indium tropolone, platelets will be reinfused in the study
participant and during the first 30 minutes dynamic and static series will be
made (t =7,8). At 3 hours (t=9), 24 hours (t=10), 48 hours (t=11), 72 hours
(t=12), 96 hours (t=13), 120 hours (t=14) and 144 hours (t=15) a static study
will be made and blood samples of 10 ml will be taken at each time point. After
2 months, the study participants will be called and asked some follow-up
questions (t=16).

This study investigates the platelet sequestration pattern in healthy subjects.
In this study the subjects will be exposed to a radiation of 1.56 mSV during
the ITP liver/ spleen scan. However, we do not expect that this dose of
radiation will cause any immediate or long term risks. The radiation dose is
safe and relatively low compared to the dose of a CT-scan of the abdomen and
pelvis is 10 mSv. Furthermore, the background radiation in the Netherlands is
about 2.5 mSv per year. No (severe) adverse events have been seen in ITP
patients who underwent the scan for diagnostic purposes. Besides the extra
radiation, blood samples will be taken from the study participants. The
required vena punction is commonly performed in general practice and almost no
adverse events are seen in healthy subjects. Hence, to our best knowledge, we
expect patients not to be exposed to any (serious) hazard in this protocol.

For the 2nd phase of the study the exposure to radioactive isotopes will be the
same as the first indium-111 scan, as the same dose of indium-111 labelled
platelets will be administered. Hence, there is no additional radiation
exposure compared to the standard scan protocol (1st ITP Liver/ Spleen scan).
Even though the study participants will undergo the ITP liver/spleen scan for
the 2nd time after 2 years, the total doses will be relatively low (1.56 mSv)
compared the standard CT thorax/ abdomen (10 mSv). Hence, we do not expect the
2nd dose of radiation will cause immediate or long-term risk for the study
participants.

Except gathering knowledge about their own sequestration pattern, there is no
direct benefit for the healthy subjects participating in this trial. However,
this study will be of great value to extend the knowledge about the normal
platelet sequestration pattern in healthy subjects. This information can be of
importance for the research to ITP and its pathogenesis. Moreover, this study
can potentially contribute in the development and improvement of diagnostics
and clinical decision making for patients with ITP.