The two thrombopoietin receptor agonists (TPO-RA), eltrombopag and romiplostim, were licensed in the US for treatment of immune thrombocytopenia (ITP) in 2008 and, since then, their use has ...progressively increased around the world; they are currently used in more than 100 countries. The six largest randomized controlled trials conducted in ITP have used one of these two agents. All studies have demonstrated a platelet response rate between 50-90%, depending on the criteria used, with good safety and tolerability. TPO-RA were shown to be effective in reducing bleeding and the need for concomitant or rescue medication. Many other investigations of their mechanism of effect, prospective and retrospective trials, and studies focusing on toxicity have been performed widening our knowledge of these two agents. Initial concerns on issues such as myelofibrosis have not been confirmed. Only a small number of patients develop moderate-severe reticulin fibrosis and/or collagen fibrosis; however, these are usually reversed after discontinuation of TPO-RA. Studies indicate, however, that TPO-RA may increase the risk of venous thromboembolism. Both TPO-RA are currently approved in patients with chronic ITP aged >1-year who are refractory to at least one other treatment. Eltrombopag has acquired two additional indications: severe aplastic anemia refractory to first-line treatment and hepatitis C patients undergoing treatment with interferon-ribavirin. Despite these wide-ranging studies, important questions still need to be answered. This summary review on TPO-RA will summarize what is known regarding efficacy in ITP, evaluate safety concerns in more depth, and focus on the questions that remain.
CAPTION(S): Table S1: Patients with reported thrombocytopenia post SARS/CoV-2 vaccination Byline: Eun-Ju Lee, Douglas B. Cines, Terry Gernsheimer, Craig Kessler, Marc Michel, Michael D. Tarantino, ...John W. Semple, Donald M. Arnold, Bertrand Godeau, Michele P. Lambert, James B. Bussel
The epidemiology of immune thrombocytopenia (ITP) is not well known. The purpose of this study was to assess ITP incidence at a nationwide level (France) with recent data (mid-2009 to mid-2011; 129 ...248 543 person-years). The data source is the French health insurance database. We selected cases with diagnosis codes for in-hospital stays and long-term disease attributions, thus restricting our search to ITPs necessitating health care. We studied incidence by age, gender, calendar month, regions, and proportion of secondary ITPs, of ITPs becoming persistent or chronic, and of severe bleeding at disease onset. We identified 3771 incident ITP patients. Incidence was 2.9/100 000 person-years, with peaks among children and in those >60 years of age. ITP was more frequent among males in these subgroups. The incidence was lower in overseas Caribbean French departments, suggesting a lower incidence among Afro-American people. There was a north-south gradient in mainland France and seasonal variations (peak in winter and nadir in summer). Persistence or chronicity occurred in 36% of children compared with 67% of adults. Among adults, 18% of ITPs were secondary. Malignancy was the main cause (10.9%). Myelodysplastic syndromes were not rare (2.3%). Severe gastrointestinal or central nervous system bleeding at ITP onset was rare (<1%).
•Incidence of ITP was 2.9/100 000 person-years with age, seasonal, and regional variations; in adults, 18% were secondary.•Severe (gastrointestinal or central nervous system) bleeding at ITP onset was rare (<1%); the risk increased with age.
The paradigm for managing primary immune thrombocytopenia (ITP) in adults has changed with the advent of rituximab and thrombopoietin receptor agonists (TPO-RAs) as options for second-line therapy. ...Splenectomy continues to provide the highest cure rate (60%-70% at 5+ years). Nonetheless, splenectomy is invasive, irreversible, associated with postoperative complications, and its outcome is currently unpredictable, leading some physicians and patients toward postponement and use of alternative approaches. An important predicament is the lack of studies comparing second-line options to splenectomy and to each other. Furthermore, some adults will improve spontaneously within 1-2 years. Rituximab has been given to more than 1 million patients worldwide, is generally well tolerated, and its short-term toxicity is acceptable. In adults with ITP, 40% of patients are complete responders at one year and 20% remain responders at 3-5 years. Newer approaches to using rituximab are under study. TPO-RAs induce platelet counts > 50 000/μL in 60%-90% of adults with ITP, are well-tolerated, and show relatively little short-term toxicity. The fraction of TPO-RA–treated patients who will be treatment-free after 12-24 months of therapy is unknown but likely to be low. As each approach has advantages and disadvantages, treatment needs to be individualized, and patient participation in decision-making is paramount.
Summary
With prolonged life expectancy, immune thrombocytopenia (ITP) is frequent in elderly people. In this setting, ITP diagnosis is challenging because of the concern about an underlying ...myelodysplastic syndrome. Studies of older adults are lacking, and recommendations for treatment are based mainly on expert opinion. The therapeutic strategy differs from that for younger patients and must take into account the greater risk of bleeding and thrombosis, presence of comorbidities, possible impaired cognitive performance or poor life expectancy and concomitant medications, such as anticoagulant and antiplatelet therapy. Steroids and intravenous immunoglobulin (IVIg) therapy remain the first‐line treatments in elderly patients, but prolonged treatment with steroids should be avoided and IVIg treatment may lead to renal failure. Splenectomy is less effective than in young patients and risk of thrombosis is increased. Severe co‐morbidities can also contraindicate surgery. Therefore, other second‐line treatments are frequently preferred. Danazol and dapsone can be an option for the less severe ITP form. Rituximab is a good option except in patients with a history of infection or with hypogammaglobulinaemia. Thrombopoietin agonists are attractive, especially for patients with severe comorbidities or with limited life expectancy but the risk of thrombosis is a concern.
Less than 40% of patients with newly diagnosed adult immune thrombocytopenia will show spontaneous recovery within 12 months. Therefore, second-line treatments are frequently used to maintain a ...hemostatic platelet count or at best to cure the disease, with as few adverse effects as possible. Nevertheless, we lack head-to-head comparison studies of the different available treatments. Moreover, physicians have no robust predictors of response to guide decision-making on an individual basis. Therefore, there is no consensus, and decisions when to treat and with which drug must be individualized and shared with the patient based on factors related to the patient and the available second-line treatments. The main treatments used, based on their good benefit-risk ratio, are splenectomy, rituximab, and thrombopoietin-receptor agonists, but their prescription should be avoided in some situations and can be limited due to cost or to health authorities' restrictions on funding the last two drugs. This review presents the various second-line treatments used in primary persistent or chronic immune thrombocytopenia in adults and discusses their prescription in general and specific situations.
Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the ...International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018. An expert panel screened, reviewed, and graded the studies and formulated the updated consensus recommendations based on the new data. The final document provides consensus recommendations on the diagnosis and management of ITP in adults, during pregnancy, and in children, as well as quality-of-life considerations.
Management of immune thrombocytopenia (ITP) during pregnancy can be challenging because treatment choices are limited. Thrombopoietin receptor agonists (Tpo-RAs), which likely cross the placenta, are ...not recommended during pregnancy. To better assess the safety and efficacy of off-label use of Tpo-RAs during pregnancy, a multicenter observational and retrospective study was conducted. Results from 15 pregnant women with ITP (pregnancies, n = 17; neonates, n = 18) treated with either eltrombopag (n = 8) or romiplostim (n = 7) during pregnancy, including 2 patients with secondary ITP, were analyzed. Median time of Tpo-RA exposure during pregnancy was 4.4 weeks (range, 1-39 weeks); the indication for starting Tpo-RAs was preparation for delivery in 10 (58%) of 17 pregnancies, whereas 4 had chronic refractory symptomatic ITP and 3 were receiving eltrombopag when pregnancy started. Regarding safety, neither thromboembolic events among mothers nor Tpo-RA-related fetal or neonatal complications were observed, except for 1 case of neonatal thrombocytosis. Response to Tpo-RAs was achieved in 77% of cases, mostly in combination with concomitant ITP therapy (70% of responders). On the basis of these preliminary findings, temporary off-label use of Tpo-RAs for severe and/or refractory ITP during pregnancy seems safe for both mother and neonate and is likely to be helpful, especially before delivery.
Summary
Rituximab and thrombopoietin receptor agonists (TPO‐RAs) have profoundly changed the management of immune thrombocytopenia (ITP) over the last 20 years. Even if most current guidelines put ...splenectomy, rituximab and TPO‐RAs on the same treatment level, most clinicians and patients clearly prefer to postpone splenectomy and to multiply the lines of medical treatment before considering surgery. The management of ITP refractory to rituximab and TPO‐RAs is challenging. Splenectomy is currently performed much less frequently because of a better knowledge of its complications, particularly severe late infections and deep vein thrombosis, and the inability to reliably predict its effectiveness. Furthermore, there is a reluctance to propose splenectomy when other treatments have been ineffective, based on the not well‐documented risk that splenectomy could not be effective in such a case. The objective of this update was to review the most recent published data on the long‐term tolerability and side effects of splenectomy and the predictors of response and efficacy, especially for patients exposed to multiple medical lines. This update can help physicians and patients with failure of multiple lines of therapy make an informed decision on the indication for splenectomy with the help of up‐to‐date data.
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