Autologous 111 Indium-Oxinate-Labelled Platelet Sequestration Study in Patients with Immune Thrombocytopenia Treated By Thrombopoietic Receptor-Agonists
Authors: Mahevas Matthieu , Van Eeckhoudt Sandrine , Moulis Guillaume , Dosquet Christine , Michel Marc , Limal Nicolas , Languille Laetitia , Alkaeir Sawsaneh , Bierling Philippe , Dossier Antoine , Duriez Frédéric , Galicier Lionel , Morin Anne-Sophie , Tamburini Jérôme , Chaoui Driss , Bouscary Didier , AL Jijakli Ahmad , Khellaf Mehdi , Vaida Ioana , Godeau Bertrand , Chomienne Christine 
Published: October 2019

Abstract
Introduction
In immune thrombocytopenia (ITP), isotopic assessment of the site of platelet destruction using autologous111Indium-oxinate-labelled platelet sequestration study could be an helpful parameter to determine whether or not to perform splenectomy. Two independent studies have suggested that a purely splenic sequestration could be a significant predictive factor of long-term complete response after splenectomy. An increasing number of patients receives thrombopoietic receptor-agonists (TPO-RAs) but such treatments are not curative and therefore do not necessarily prevent from considering splenectomy in the course of ITP. TPO-RAs increase platelet production by inducing proliferation and differentiation of the megakaryocyte lineage. We have only very few data evaluating the impact of TPO-RAs, on mean platelet life span (MPLS), platelet production and platelet site of destruction. The aim of this study was to assess these parameters and clinical outcome of patients treated with TPO-RAs who underwent kinetic study of autologous111Indium-oxinate-labelled platelet.
Patients and Methods
We carried out a retrospective study in the Ile de France region, between 2008 and 2016. Patients were retrospectively selected from a prospective clinical database at the Cellular Biology Department of Saint Louis Hospital. We selected adult patients with definite ITP according to the international criteria. The isotopic method used to study platelet lifespan was previously described. Analyses were based on the radioactivity accumulation slopes in the hepatic or splenic area. We excluded patients who had received less than 3Mbeq of 111In. Data from patients' medical charts were collected using the standardized form of the Referral Center for Adult ITP. Complete response (CR) and Response (R) were defined according to standardized international criteria: platelet count > 30x 109/L with at least a doubling of the baseline value or >100 x 109/L. Results of platelet kinetic study from patients treated with TPO-RAs were compared with those from patients receiving no treatments.
Results
Two hundred and fifty three adults ITP patients were included. At the time of platelet kinetic study, 24 patients (10 men/14 women) with a median age of 63 years [range: 22-83] were treated with TPO-RAs (romiplostim n= 10, eltrombopag n = 14) and 229 (81 men/148 women) had no treatment. Among the TPO-RAs treated patients, some also received low dose steroids (n=6), dapsone (n=1) or intravenous immunoglobulins (n=2) at least two weeks before the kinetic study. Three were newly diagnosed, 9 had persistent ITP and 12 chronic ITP. The median platelet count was 62 x109/L [range: 22-175], and 7 patients had a platelet count > 100 x109/L. The median Mean Platelet Life Span (MPLS) was reduced in both groups (1.44 day [range: 0.4-7.5] (normal: 7-10) in patients treated with TPO-RAs), but was significantly higher in untreated patients (2.3 day [0.4-11], p = 0.004). The median turnover platelets ratio was increased in both groups (48% per day [range: 11-173] in patients treated with TPO-RAs), but was significantly lower in untreated patients (30% per day [range: 0.8-247]). Ratio of platelet production was significantly increased in patients treated with TPO-RAs (median: 2, [range: 0.1-5.0]) compared with untreated patients (median: 0.84, [range: 0.1-85.0]). Repartition of the site of platelet sequestration was similar in the two groups, 12 (50%) patients treated with TPO-RAs had a splenic uptake, versus 112 (49.1%) in untreated patients, and 2 (20%) patients treated with TPO-RAs had an hepatic uptake versus 9 (3.9%) in untreated patients. A splenectomy was performed in 9 out of the 12 patients with a purely splenic sequestration. After a median follow-up of 26 months [range 0-53], 8 (88%) had achieved CR and 1 had relapsed 5 months after splenectomy.
Conclusion
Our study shows that despite an increase production and turnover of platelets due to the stimulation of the megakaryopoiesis by TPO-RAs, the MPLS was clearly reduced and the repartition of platelet sequestration was not modified in patients receiving these drugs. Moreover, it would seem that a purely splenic sequestration is also predictive of CR after splenectomy in this group of patients. More importantly platelet kinetic study can be used in patients treated with TPO-RAs to position the splenectomy in the therapeutic management.

Disclosures
No relevant conflicts of interest to declare.