Introduction Immune thrombocytopenia (ITP) is characterized by low platelet counts due to high clearance and low production. Better insight in the pathophysiology of ITP is needed to personalize management regimes, especially in patients with persisting and chronic ITP. In the Haga Teaching Hospital, we reproduced and validated the ITP liver/spleen scan from St Bartholomew's Hospital in London. With this scan the in vivo sequestration patterns of platelets in either spleen, liver or a combination of both (mixed sequestration) can be assessed, by using Indium-111 labelled autologous platelets . The ITP liver/spleen scan may provide better insights in autoantibody-mediated platelet destruction in ITP patients. Autoantibodies directed against glycoprotein (GP) IIb/IIIa, Ib/IX and V namely are found in a majority of ITP patients and can be detected using specific assays, like platelet immunofluorescence test (PIFT) and Monoclonal Antibody Immobilization of Platelet Antigen (MAIPA). To the best of our knowledge no studies have investigated the possible association between sequestration patterns and glycoproteins. In this study we investigated associations between the sequestration patterns from the ITP liver/spleen scan and the presence of different anti-GP platelet antibodies.
Methods All ITP patients receiving an ITP liver/spleen scan between 2014 and 2016 in the Haga Teaching Hospital, a large tertiary referral centre in the Netherlands, are collected from our electronic patient files. We retrospectively collected demographic and clinical characteristics, including duration of ITP, previous management of ITP (corticosteroids, rituximab, thrombopoietin receptor agonists (TPO-RA)), antibody assays (PIFT, direct and indirect MAIPA) and the results from the ITP liver/spleen scan. MAIPA is used as a continuous variable. To investigate the association between anti-GP antibodies and the sequestration pattern from the ITP liver/spleen scan we used linear regression models for the continuous variables and logistic regression models for the binary data. Observational data and scatter plots aid in the interpretation of the possible associations. Both univariate and multivariate regression models including age and sex will be performed.
Results 55 ITP patients with a median age of 41 years (IQR 29-57) and 67% females underwent an liver/spleen scan in the study period. The median age of the cohort at diagnosis of ITP was 32 (IQR 22-54) years. Treatment history consisted of corticosteroid therapy in 96% of cases, 44% IVIG, 48% TPO-RA and 21% rituximab. 10% of patients received only 1 treatment line, 23% received 2 lines, 33% received 3 lines, 21% 4 lines, 10% 5 lines and 1 patient received 7 lines (2%). Clinical significant bleedings (WHO bleeding grade ≥2) were reported by 53%, and 8% of the patients received a transfusion in the past. Sequestration pattern of the ITP liver/spleen was in 51% of cases a splenic pattern vs. 49% a mixed/hepatic pattern. A significantly higher prevalence of a splenic pattern was present in patients under 30 years at diagnosis while patients older than 30 years showed a more mixed/hepatic pattern. Anti-glycoprotein antibodies were found in 54% of the patients. Interestingly, linear regression models showed no association between either anti-GPIIb/IIIa or anti-GPIb/IX antibody detection and sequestration pattern. However a significant association was observed between the presence of anti-GPV antibodies and sequestration pattern. A higher anti-GPV antibody level and/or affinity was associated with a higher level of splenic sequestration.
Conclusions This study has shown that the presence of anti-GPV antibodies is associated with a splenic sequestration pattern in the ITP liver/spleen scan in patients suffering from persistent and chronic ITP. GPV is usually found as a complex with GPIb/IX in several other bleeding disorders. Surprisingly no association was found in our data between a splenic sequestration pattern and the presence of anti-GPIIb/IIIa and especially anti-GPIb/IX. Further studies are needed to clarify the possible role of anti-GPV antibodies in thrombocyte clearance by the spleen in ITP patients.
Amini: AMGEN: Research Funding. Schutgens: Baxalta/Shire: Research Funding; Novo Nordisk: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding; Pfizer: Research Funding; Uniqure BV: Research Funding. Schipperus: AMGEN: Research Funding; Novartis: Research Funding.
Asterisk with author names denotes non-ASH members.