Review Series CLINICAL PLATELET DISORDERS Clinical updates in adult immune thrombocytopenia Michele P. Lambert 1 and Terry B. Gernsheimer 2 1 Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, PA; and 2 Division of Hematology, University of Washington School of Medicine, Seattle, WA Immune thrombocytopenia (ITP) occurs in 2 to 4/100 000 adults and results in variable bleeding symptoms and thrombocytope- nia. In the last decade, changes in our understanding of the pathophysiology of the disorder have led to the publication of new guidelines for the diagnosis and management of ITP and standards for terminology. Current evidence supports alternatives to splenectomy for second- line management of patients with persis- tently low platelet counts and bleeding. Long-term follow-up data suggest both efficacy and safety, in particular, for the thrombopoietin receptor agonists and the occurrence of late remissions. Follow-up of patients who have undergone splenec- tomy for ITP reveals significant potential risks that should be discussed with pa- tients and may influence clinician and patient choice of second-line therapy. Novel therapeutics are in development to address ongoing treatment gaps. (Blood. 2017;129(21):2829-2835) Introduction Immune thrombocytopenia (ITP) is an acquired thrombocytope- nia, defined as a platelet count ,100 3 10 9 /L, and caused by immune destruction of platelets. 1 It occurs in both adults and children, with a multimodal incidence with 1 peak in childhood and second and third peaks in young adults and the elderly. The underlying disease process in childhood ITP and adult ITP may be fundamentally different, as evidenced by the rate of chronic ITP in these patient populations. 2 Although the majority of children have self-limited disease, in adults, ITP is more often a chronic disorder. In 2010 to 2011, the American Society of Hematology (ASH) 3 and an international consensus report 4 both published guidelines for the diagnosis and management of ITP. In 2009, an International ITP Working Group (IWG) also published recom- mendations for standardization of definitions and terminology to allow for alignment of research studies and eventually aid in management of patients with ITP. 1 The IWG defined the abbreviation in common use (ITP) to be Immune Thrombocyto- penia (neither Idiopathic nor Purpura) because the pathophysi- ology is better understood and the majority of both adult and pediatric patients do not present with purpura, 5 even if they have petechiae and bruising. 1 The IWG also removed the term “acute” ITP, as this diagnosis can only be made in retrospect, after the patient has recovered from the thrombocytopenia. Instead, they proposed standardized terminology, which is outlined in Table 1. Since the publication of these seminal papers to help define and guide the diagnosis and management of ITP, research has continued into optimal therapy, diagnostic evaluation, and prognostic indicators for adults with ITP. New evidence suggests that some populations of patients may be safely observed, and the development of the thrombopoietin receptor agonists (TPO-RA) have changed the landscape of management of chronic disease. The purpose of this review is to summarize the recent clinical development in diagnosis and management of adults with ITP. Epidemiology of ITP The incidence of primary ITP in adults is 3.3/100 000 adults per year with a prevalence of 9.5 per 100 000 adults. There is a predilection for female patients in younger adults, but the prevalence of ITP in men and women is fairly even in the elderly (.65 years). 6-8 A recent meta- analysis looked at risk of thrombosis in adult patients with ITP and concluded that patients with ITP have a higher risk of thromboembo- lism (TE) after ITP diagnosis of 1.6 (1.34, 1.86) based primarily on 2 large cohort studies. 9 Interestingly, this same analysis showed a risk of TE prior to the ITP diagnosis in these patients with a prevalence of ;8%. 9 Secondary ITP (ITP associated with other disorders) makes up ;20% of ITP diagnoses 10 and is part of the reason that some patients undergo extensive diagnostic evaluations at the time of diagnosis. However, the prevalence of autoimmune disease in the ITP population without additional signs/symptoms was quite low in the largest population-based study examining ITP by using the United Kingdom General Practice Research Database, where it was 8.7%. 7 In a French epidemiological study, the incidence of secondary ITP was 18%. 8 Population studies also suggest an increased mortality for patients with ITP compared with the general population, with risk of mortality likely related to severity of disease. A Danish study reported a 1.5-fold higher mortality in ITP patients compared with the general population, with significant increased risk of bleeding and infection (relative risk [RR], 2.4 and 6.2, respectively) as well as hematologic malignancy (RR, 5.7). 11 Subsequent studies have not confirmed the increased risk of malignancy. 12 Pathophysiology In the last several years, our understanding of the pathophysiology of ITP has significantly improved. It is now clear that Primary ITP is an acquired immune disorder where the thrombocytopenia results from Submitted 13 March 2017; accepted 10 April 2017. Prepublished online as Blood First Edition paper, 17 April 2017; DOI 10.1182/blood-2017-03-754119. © 2017 by The American Society of Hematology BLOOD, 25 MAY 2017 x VOLUME 129, NUMBER 21 2829 For personal use only. on March 6, 2018. by guest www.bloodjournal.org From