Adult Primary Immune Thrombocytopenia Research Articles

Risk and prognosis of adult primary immune thrombocytopenia

Adult immune thrombocytopenia was previously considered a benign disease affecting young people and with a low risk of severe bleeding. This view was challenged by studies published during the past decade, as the median age of adult immune thrombocytopenia patients has been found to be 55–60 years and the incidence increases with age. Recent studies reported that mortality and morbidity are increased compared with the general population. In this review, we describe patient-specific factors associated with the outcome of disease, the clinical course of immune thrombocytopenia including the potential adverse impact of some treatments and finally the overall prognosis.

Revisiting Splenectomy in Childhood Chronic Immune Thrombocytopenia At the Era of New Therapies: The French Experience

Abstract▪2227▪This icon denotes a clinically relevant abstract Background:While splenectomy is the gold standard treatment for adult's refractory primary immune thrombocytopenia (ITP), its place remains debated in children. The Rare Disease Plan gave us the opportunity to conduct a French collaborative work aiming to study efficiency, tolerance and prognostic factors associated with success of this procedure in childhood ITP. Design and methods:A retrospective study was conducted in France, of less than 18 years old children and adolescents who underwent a splenectomy for ITP during a 9-year period (2000–2009). Data from both the CEREVANCE national cohort and systematic requests to 30 paediatric units were reviewed. Medical data and procedures were checked from patients’ medical records. Complete remission (CR) was defined by platelet count of more than 100 G/L, continuous complete remission (CCR) was defined as CR with no relapse or treatment for at least one year (Aladjidi et al, Haematologica 2011). Relapse-free survival was assessed by Kaplan Meier method. Results:For 78 children in 16 units, the median ages at diagnosis of ITP and at splenectomy were respectively 9.6 (0.8–16.5) and 12.4 (3.5–17.4) years. The median duration of ITP before splenectomy was 24 months (1–162), 62 children had chronic ITP of more than 12 months duration. The surgical procedure was laparoscopy in 81% of children. Four patients experienced post-operative complications: 1 severe intra-abdominal hemorrhage requiring open surgery twelve hours after laparoscopy, 1 pleural and peritoneal hemorrhage after laparotomy, 1 mesenteric and splenic thrombosis and 1 pulmonary atelectasia. With a median follow up of 41 months (1–109), CR and CCR were achieved respectively for 83% and 75% of 62 children with chronic ITP. No overwhelming sepsis was reported during the follow-up. Isotopic platelet studies were available in 10 of the 16 units and assessed in 30 of the 44 concerned children. CR was obtained in 77% of 26 cases with predominant splenic destruction, and in 0% of 2 cases with non splenic destruction. Five-year relapse-free survival was 35% in children of less than 10 years old and 81% in children of more than 10 years old at initial diagnosis of ITP (p=0.0002). Conclusion:This collaborative national study confirms the excellent benefit-risk ratio of splenectomy for refractory chronic ITP, especially in older children. Even if our own results are limited by the small number of patients, prior isotopic platelet studies is useful when locally available. Long term respect of anti-infectious measures is recommended.Acknoledgements to the Association Française pour le Syndrome d’Evans (AFSE), the GIS - Institut des Maladies Rares - INSERM, and the French Health Ministry (Programme Hospitalier de Recherche Clinique 2005, Rare Diseases Plan 2007). Disclosures:No relevant conflicts of interest to declare.

Recombinant Human Thrombopoietin (rh-TPO) in Combination with Rituximab As a Novel Therapy in Corticosteroid-Resistant Primary Immune Thrombocytopenia (ITP)

Abstract▪2223▪This icon denotes a clinically relevant abstract Background:Both thrombopoietin (TPO) receptor agonist and rituximab were recommended as second-line options for adult primary immune thrombocytopenia (ITP) according to the 2010 International Consensus Guideline. The mechanism of rituximab therapy mainly refers to inhibition of accelerated platelet destruction mediated by autoantibody, while the latter, TPO receptor agonist, is reported to be effective in the salvage of impaired platelet production in patients. Despite the considerable response rate (about 50–70%) and sustained response (about 20–40%), the median time to response (TTR) was about 5.5 weeks for patients undergoing rituximab therapy, indicating high bleeding risk in the early stage of the treatment (Arnold, et al. Ann Intern Med. 2007;146:25–33.). On the other hand, novel TPO receptor agonists could initiate fast but unenduring responses. We hereby report a novel therapy which combines low-dose rituximab with short-term application of a TPO receptor agonist, the recombinant human thrombopoietin (rh-TPO), based on the preliminary results of an ongoing multi-centered, non-randomized clinical study in corticosteroid-resistant adult ITP patients. Patients:Twenty-one adult ITP patients were enrolled since December, 2009. All the subjects had a baseline platelet count (PC) of <30×109/L or bleeding, were refractory to, or had relapsed after, at least one prior corticosteroids therapy and splenectomy, or acquired corticosteroid-resistance but were excluded from splenectomy, without application of other second-line therapies recommended in the Guideline in the previous 3 weeks. Methods:Rituximab was given intravenously at a dose of 100 mg weekly for 4 consecutive weeks (Day 1, 8, 15, 22). Rh-TPO (TPIAO™, a product of Sunshine Pharmaceutical Co Ltd, China, approved by China State Food and Drug Administration) was given subcutaneously at a dose of 1.0 μg/kg daily for 14 days (Day 1–14). PC was monitored every three or four days until day 22, followed by tests every week. Responses were required to be independent of measures and supportive platelet transfusion. The criteria for response were defined as follows: (1) complete response (CR): platelet count >100×109/L and; (2) response (R): platelet count>30×109/L and at least 2-fold increase the baseline count and absence of bleeding; (3) No response (NR): platelet counts <30×109/L or less than 2-fold increase of baseline platelet count or bleeding. TTR: times from starting treatment to time of achievement of CR or R. Patients were followed for 3 months, and any adverse effects were recorded during the period of treatment and during the follow-up. Results:All the patients received the therapy, but 4 were lost during follow-up. The efficacy of treatment is outlined in Table 1. Compared with rituximab alone, the combination therapy resulted in a rapid response (TTR 9 vs. 21–44 days) with similar response rate (CR 57% vs. 30–60%, OR 76% vs. 50–70%). Moreover, the rh-TPO seemed to not only shorten the TTR but also significantly increase the sustained response (69% vs. 20–40%), indicating a synergistic effect with rituximab. In addition, there was no toxicity overlap observed. Adverse events recorded were mild (WHO grades 1–2), including fever (2), fatigue (2), myalgia (2), secondary infection (2), chills (1),and insomnia (1). No serious adverse events occurred during the course of treatment and the period of follow-up. Conclusions:The efficacy of this novel combination therapy are very satisfactory, considering the higher overall and complete response, shorter TTR as well as higher sustained response, in comparison with administrating rituximab alone. However, the combination should be used with caution and needs further and larger scale observation, especially to monitor for serious adverse effects such as thrombosis, bone marrow fibrosis and infection.Table 1Median Age (range)Sex (M/F)Baseline Median PC (×109/L)CRRORSRNRTTR (Days)N = 2147(20–74)9/128(0–32)57.14% (12)19.05% (4)76.19% (16)69.23% (9/13)23.81% (5)9 (4–22)*CR: complete response; R: response; OR: overall response; SR: sustained response at the end of the trial; NR: no response; TTR: time to response. Disclosures:No relevant conflicts of interest to declare.

PSY27 Cost-Consequence Analysis Comparing Romiplostim to Rituximab in the Treatment of Adult Primary Immune Thrombocytopenia (Itp) in France

PSY27 Cost-Consequence Analysis Comparing Romiplostim to Rituximab in the Treatment of Adult Primary Immune Thrombocytopenia (Itp) in France

Chronic adult primary immune thrombocytopenia (ITP) in the Asia-Pacific region

Patients with primary immune thrombocytopenia (ITP) from the Asia-Pacific region often exhibit characteristics distinct from those of patients from the West. Moreover, as the region itself is heterogeneous, the ITP landscape among individual Asia-Pacific countries can be diverse. The recently released international consensus report on ITP places new emphasis on ITP, but does not address the unique ITP landscape in the Asia-Pacific region, which is home to 60% of the world's population. In an attempt to characterize how the ITP landscape differs between the West and the Asia-Pacific region, an expert panel with representatives from Northeast Asia, Southeast Asia, and Australia was convened. Important differences were identified between the guidance provided in the international consensus report and experience in the Asia-Pacific region, namely diagnostic practices, incidence and approach to ITP secondary to H. pylori infection, systemic lupus erythematosus-related ITP, the use of bone marrow examination, initial treatment strategies, and the role of splenectomy, rituximab, and thrombopoietin receptor agonists.

Immune Thrombocytopenia

Immune thrombocytopenia (ITP) comprises a heterogeneous group of disorders characterized by autoimmune-mediated platelet destruction and impairment of thrombopoiesis. ITP may occur in the absence of an evident predisposing etiology (primary ITP) or secondary to a growing list of associated conditions (secondary ITP), and must be differentiated from other causes of thrombocytopenia. This review focuses on primary ITP in adults. The traditional goal of therapy in this population is to achieve a hemostatic platelet count of 30×10(9)/L or above for most patients while minimizing treatment-related morbidity. This approach has been called into question by the recent advent of well-tolerated and effective agents for the management of ITP, including pulse-dose dexamethasone, rituximab, and the thrombopoietin receptor agonists. Recent studies suggest the potential for aggressive therapy at the time of diagnosis to alter the natural history of ITP and point to the importance of quality-of-life considerations in therapeutic decision making.

Treatment of eczema in breast fed infants: Sprenkel, V.: Arch. Pediat. 55: 85, 1938

First described in 1735 (Watson-Williams et al., 1958 [1]), immune-mediated platelet destruction is a phenomenon of protean associations that has historically varied in its definition. Recently, consensus guidelines were proposed for a standardized system of nomenclature that preserves the acronym “ITP” but encompasses a number of causes of immune-mediated thrombocytopenias, including both primary immune thrombocytopenia as well as such entities as thrombocytopenia associated with connective tissue diseases or cancer. In this paper, we will focus on current aspects of geoepidemiology, pathophysiology, diagnosis and management of adult and pediatric primary immune thrombocytopenia. It is clear that both genetic and extrinsic factors exist for ITP and are likely different between children and adults. Immune thrombocytopenia remains a challenging problem but our understanding of its pathophysiology has greatly improved.