Adults with primary immune thrombocytopenia (ITP) may be susceptible to thromboembolism (TE). The objective of this systematic review was to evaluate studies that reported the prevalence and risk of developing TE in the ITP population from ITP diagnosis and splenectomy. We searched several bibliographic databases and included 29 studies. Using meta-analytical techniques, the pooled prevalence of TE before ITP diagnosis was 7.84% (arterial 6.25%; venous 1.95%). The pooled 'annualised' cumulative incidence (without prior TE) and cumulative risk (irrespective of prior TE) were 1.29%/yr and 3.00%/yr, respectively. Splenectomised patients had pooled cumulative risk of arterial TE (ATE) and venous TE (VTE) of 0.19%/yr and 1.10%/yr, respectively. In cohorts, regardless of a history of TE, the pooled relative risk (RR) of any TE was 1.60 (1.34, 1.86) for ITP vs. ITP-free individuals [arterial: 1.52 (1.25, 1.80); venous: 1.70 (0.96, 2.43)]. Splenectomised patients were at higher risk of venous events, pooled RR 2.39 (1.61, 3.17). To conclude, we found an increased risk of TE (mainly ATE) among ITP individuals and a higher risk of VTEs after splenectomy. How intrinsic (ITP pathophysiology, age, gender) and extrinsic factors (treatment) contribute to this risk could not be investigated here but is a task for future studies. Primary immune thrombocytopenia (ITP) in adults is a rare heterogeneous blood disorder which is characterised by a reduced peripheral blood platelet count below 100 9 10 9 /L (1). Its underlying mechanisms are increasingly explained within an 'autoimmune' paradigm in which platelets are destroyed through antibody-mediated destruction and thrombocytopoiesis is reduced through immune-mediated megakaryocytic downregulation (2).Although bleeding is a prominent feature of the disease, patients often present with other comorbid conditions at ITP diagnosis or throughout the course of the disease (3, 4). Notably, there are studies that showed that the risk of thromboembolic events (TE) could be elevated among patients with ITP (4, 5) and also among patients who had ITP-related splenectomies (6). How such a paradoxical 'prothrombotic and thrombocytopenic' state coexists is not completely understood. One likely explanation for this heightened risk for TE is that the ITP pathophysiology promotes a prothrombotic state but the evidence is unclear and weak (7-9). On the other hand, the distribution and influence of typical prothrombotic risk factors, including obesity, smoking, family history of TE, and the impact of ITP-related treatments, such as long-term corticosteroid use or splenectomy, on the risk of TE in ITP have been not completely described and explained. Before engaging into investigative studies on the contributory factors of TE in ITP, it is important to review the published evidence to date to establish whether there is a heightened risk of TE in the ITP population.

Summary Fibrosis has been reported in some patients with immune thrombocytopenia (ITP) treated with thrombopoietin receptor agonists (TPO‐RA). However, fibrosis has also been reported in patients with various stages of ITP, who were TPO‐RA treatment‐naïve. In our study, we looked for fibrosis in bone marrow trephine biopsies taken at initial diagnosis from 32 adult patients with ITP. Ten of the 32 evaluated samples (31·25%) showed increased reticulin (Grade 1–2 on Bauermeister scale and Grade 0–1 on the European Consensus scale), which showed a positive correlation with ethnicity (0·3%) but did not correlate with disease severity, any clinical features or co‐morbidities.

BackgroundRomiplostim is a thrombopoietin‐mimetic peptibody for adult refractory chronic immune thrombocytopenia (ITP). We aimed to describe ITP patients receiving romiplostim, platelet counts and romiplostim usage in UK clinical practice.MethodsThis was a retrospective cohort study of patients in the UKITP Registry who received romiplostim between October 2009 and January 2015, including data up to 6 months before romiplostim initiation through follow‐up.ResultsOf 1440 patients in the UKITP Registry, 118 adults with primary ITP were eligible. Before romiplostim, 22% had splenectomy, 12% received platelet transfusion, 97% received ≥ 1 different ITP medication and 77% received ≥ 3. Most patients (73%) initiated romiplostim ≥ 1 year after ITP diagnosis (chronic phase). The mean duration of romiplostim treatment was 5.7 (SE 0.9) months, and the median was 1.4 months (IQR: 0.2, 6.5). Mean platelet count before romiplostim was 38 × 109/L, rising to 103 × 109/L within 1 month, and remaining 50‐150 × 109/L through up to 3 years of follow‐up. After romiplostim, 4% of patients had splenectomy, 6% received platelet transfusion, and 57% received just one ITP medication other than romiplostim.ConclusionThe study provides valuable insights into the real‐world use of romiplostim in primary ITP in routine practice and highlighted the timing of romiplostim initiation at different ITP disease phases.

P rimary immune thrombocytopenia is an autoimmune disorder in which platelet destruction is a consequence of both B-and T-cell dysregulation. Flow cytometry was used to further characterize the B-and T-cell compartments in a cross-sectional cohort of 26 immune thrombocytopenia patients including antiplatelet antibody positive (n=14) and negative (n=12) patients exposed to a range of therapies, and a cohort of matched healthy volunteers. Markers for B-cell activating factor and its receptors, relevant B-cell activation markers (CD95 and CD21) and markers for CD4 + T-cell subsets, including circulating T-follicular helper-like cells, were included. Our results indicate that an expanded population of CD95 + naïve B cells correlated with disease activity in immune thrombocytopenia patients regardless of treatment status. A population of CD21-naïve B cells was specifically expanded in autoantibody-positive immune thrombocytopenia patients. Furthermore, the B-cell maturation antigen, a receptor for B-cell activating factor, was consistently and strongly up-regulated on plasmablasts from immune thrombocytopenia patients. These observations have parallels in other autoantibody-mediated diseases and suggest that loss of peripheral tolerance in naïve B cells may be an important component of immune thrombocytopenia pathogenesis. Moreover, the B-cell maturation antigen represents a potential target for plasma cell directed therapies in immune thrombocytopenia.