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Treatment Options for Thrombocytopenia in Patients With

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Treatment Options for Thrombocytopenia in Patients With CLINICAL REVIEW Treatment Options for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing a Scheduled Procedure Sammy Saab, MD, MPH, AGAF, FACG, FAASLD,* David Bernstein, MD,† Tarek Hassanein, MD, FACP, FACG, AGAF, FAASLD,‡ Marcelo Kugelmas, MD, FACP, FAASLD,§ and Paul Kwo, MD∥ 05/07/2020 on BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3y7wDLvMZ9kx3JdIy0LawIg5rEJxBYFsykIQcrqA+4sY= by https://journals.lww.com/jcge from Downloaded Downloaded lthough thrombocytopenia, that is, reduction of platelet from Abstract: Thrombocytopenia is a consequence of portal hypertension A count in the blood, is the single most common hema- https://journals.lww.com/jcge and is the most common hematological manifestation of chronic liver tological manifestation of chronic liver disease (CLD), disease (CLD) (ie, cirrhosis). Data indicates the rates of CLD are published literature on this topic is scarce. As the incidence increasing and, as a result, so will the incidence of this complication. of thrombocytopenia in CLD is 70% in patients with cir- Although bleeding risks are only relevant when elective procedures are performed, this is a frequent concern as these procedures are commonly rhosis versus 6% in patients without cirrhosis, for the pur- part of the spectrum of care for patients with cirrhosis. As such, poses of our understanding of thrombocytopenia, CLD by thrombocytopenia remains a pertinent issue. Fortunately, we now have essentially refers to cirrhosis throughout this review. In the BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3y7wDLvMZ9kx3JdIy0LawIg5rEJxBYFsykIQcrqA+4sY= effective and accurate treatment modalities to raise platelet counts before United States, nearly 4 million adults (1.6% of the pop- scheduled procedures, known as thrombopoietin receptor agonists. Two ulation) have CLD.1 In fact, CLD and cirrhosis were the drugs in this therapeutic class (avatrombopag and lusutrombopag) are 12th leading cause of death in the United States in 2015, now approved for the treatment of thrombocytopenia in adults with taking the lives of over 40,000 patients in that year.2 An CLD undergoing a procedure and have revolutionized how this is fi epidemiology study published that same year reported a managed. Although there is progress in the eld, peer-reviewed literature 2-year mortality rate of 26.4% for patients with cirrhosis.3 and expert guidance are lacking. Recognizing these unmet needs, a group of expert hepatologists comprised this review, which summarizes the According to the American Association for the Study of most current and relevant peer-reviewed literature on thrombocytopenia Liver Diseases (AASLD), cirrhosis is a heterogeneous disease 4 in CLD and provides clinical expertise on this timely topic. that cannot be studied or managed as a single entity. As such, this advanced form of liver disease is most commonly the Key Words: thrombocytopenia, chronic liver disease, treatment, result of nonalcoholic fatty liver disease, chronic hepatitis C procedure virus (HCV), and alcoholic liver disease. These diseases pose a fi (J Clin Gastroenterol 2020;00:000–000) signi cant burden to patients and providers and are continu- ing to increase in prevalence (Table 1). In fact, a recent pop- ulation-based study from Kim and colleagues provided an updated estimate of the burden and etiology-specific mortality From the *David Geffen School of Medicine at UCLA, Los Angeles; ‡Southern California Research Center, San Diego; ∥The Stanford of CLDs in the United States. They found that between 2007 University Medical Center, Palo Alto, CA; †Northwell Health, and 2013, there was a decrease in HCV-related mortality, Manhasset, NY; and §South Denver Gastroenterology, PC, Engle- which coincided with the introduction of the highly effective wood, CO. direct-acting antiviral therapies. Conversely, mortality from S.S.: has worked as a speaker, consultant, and advisory board member for alcoholic liver disease and nonalcoholic fatty liver disease AbbVie, BMS, Eisai, Dova, Gilead, Intercept, and Salix and received 12 research funding from Conatus. D.B.: has worked as a consultant for increased during the same period. Furthermore, as described Shionogi and Dova and received research funding from Dova. T.H.: in the table, the effects of CLD are becoming more noticeable has received research funding from Shionogi. M.K.: has served as a in a younger cohort of patients,8,13 even with regard to HCV. speaker, a consultant, and an advisory board member for Dova and on Shionogi and has received research funding from Dova. P.K.: has Other less common causes of cirrhosis include chronic hep- 05/07/2020 worked as an advisor for AbbVie, Arrowhead, Ferring, Durect, atitis B, autoimmune hepatitis, exposure to toxic chemicals Edigene, Surrozen, Eisai, Gilead, Conatus, Quest, Shionogi and and/or drugs, bile duct disorders, and inherited conditions.14 Dova; received research funding from Allergan, Assembly, AbbVie, As the burden of CLDs increase, so will the prevalence of BMS, Gilead, La Jolla Pharmaceuticals, owns stock in Durect; and has served on the DSMB for Jansen, and the Ribavirin Pregnancy cirrhosis and cirrhotic complications. Portal hypertension is the Registry. Writing support was provided by Rachel E. Bejarano, initial and main consequence of cirrhosis and is responsible for PharmD, and funded by a grant from Dova Pharmaceuticals. the majority of its complications,4 including thrombocytopenia. Address correspondence to: Sammy Saab, MD, MPH, AGAF, FACG, Thrombocytopenia is classified according to platelet count as FAASLD, David Geffen School of Medicine at UCLA, Los mild ( > 75,000 to <150,000/μL), moderate (50,000 to 75,000/ Angeles, CA 90095 (e-mail: [email protected]). 15 Supplemental Digital Content is available for this article. Direct URL μL), or severe (< 50,000/μL; Fig. 1). The presence of severe citations appear in the printed text and are provided in the HTML thrombocytopenia can significantly complicate the routine care and PDF versions of this article on the journal’s website, www.jcge. of cirrhotic patients; standard procedures (eg, liver biopsies, com. medically-indicated surgeries) can pose a substantial risk of Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, 16–18 Inc. This is an open-access article distributed under the terms of the bleeding. As such, most guidelines established by major Creative Commons Attribution-Non Commercial-No Derivatives medical societies recommend treatment interventions for License 4.0 (CCBY-NC-ND), where it is permissible to download patients with platelet counts <50,000/µL to reduce bleeding and share the work provided it is properly cited. The work cannot be 19–21 changed in any way or used commercially without permission from risk. In 2018, 2 new drugs, avatrombopag and lusu- the journal. trombopag, were approved by the Food and Drug Admin- DOI: 10.1097/MCG.0000000000001338 istration (FDA) for thrombocytopenia in adults with CLD J Clin Gastroenterol Volume 00, Number 00, ’’ 2020 www.jcge.com | 1 This paper can be cited using the date of access and the unique DOI number which can be found in the footnotes. Saab et al J Clin Gastroenterol Volume 00, Number 00, ’’ 2020 TABLE 1. The Increasing Burden of CLD Type of CLD Epidemiology Data Epidemiologic Projections NAFLD Approximately 26% of adults in the United States The burden of NASH is expected to increase from 16.5 million have NAFLD; 3%-5% have nonalcoholic in 2015 to 27 million in 2030 because of increased rates of steatohepatitis* (NASH; defined as > 5% hepatic contributing factors (obesity and diabetes mellitus)5 steatosis and inflammation with hepatocyte injury)† HCV According to the CDC, ~3.5 million people in the Cases reported to the CDC tripled from 2010 to 20156 United States have HCV.‡ Increasing cure rates The highest overall number of new infections is now among may have resulted in a decrease in prevalence 20- to 29-year-old because of increasing injection opioid use In 2015, ~20,000 deaths were attributed to HCV6 and increased transmission6 Most commonly seen in patients born from 1945 to Unlike baby boomers, young patients have no concentrated 1965 (ie, baby boomers),§ who are HCV-screening efforts and are not engaged in the health at a much greater risk of HCV-related mortality6 care system ALD In 2015, of the 78,529 liver disease deaths among The National Epidemiologic Survey on Alcohol and Related individuals aged 12 and older, 47% involved Conditions was administered to ~80,000 patients, revealing alcohol∥ that, between 2001-2002 and 2012-2013, 12-month alcohol Approximately 15.1 million adults had AUD use, high-risk drinking, and DSM-IV AUD increased by in 20157 11.2%, 29.9%, and 49.4%, respectively. Investigators deemed this a “public health crisis”¶ Among all deaths from cirrhosis in 2013, 47.9% were alcohol-related; this was highest in patients aged 25-34 (76.5%), followed by patients aged 35-44 (70%).8 *Estes et al.5 †Chalasani et al.9 ‡Hepatitis C FAQs for Health Professionals.6 §Hepatitis C.10 ∥Alcohol Facts and Statistics.7 ¶Grant et al.11 ALD indicates alcoholic liver disease; AUD, alcohol use disorder, defined by the National Institute on Alcohol Abuse and Alcoholism as a chronic relapsing brain disease characterized by compulsive alcohol use, loss of control over alcohol intake, and a negative emotional state when not using; CDC, centers for disease control; DSM, diagnostic and statistical manual of mental disorders; FAQ, frequently asked questions; HCV, hepatitis C
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