A systematic literature review on the use of platelet transfusions in patients with thrombocytopenia

ABSTRACT

Objective: Investigate globally, current treatment patterns, benefit-risk assessments, humanistic, societal and economic burden of platelet transfusion (PT).

Methods: Publications from 1998 to June 27, 2018 were identified, based on databases searches including MEDLINE®; Embase and Cochrane Database of Systematic Reviews. Data from studies meeting pre-specified criteria were extracted and validated by independent reviewers. Data were obtained for efficacy and safety from randomized controlled trials (RCTs); data for epidemiology, treatment patterns, effectiveness, safety, humanistic and societal burden from real-world evidence (RWE) studies; and economic data from both.

Results: A total of 3425 abstracts, 194 publications (190 studies) were included. PT use varied widely, from 0%–100% of TCP patients; 1.7%–24.5% in large studies (>1000 patients). Most were used prophylactically rather than therapeutically. 5 of 43 RCTs compared prophylactic PT with no intervention, with mixed results. In RWE studies PT generally increased platelet count (PC). This increase varied by patient characteristics and hence did not always translate into a clinically significant reduction in bleeding risk. Safety concerns included infection risk, alloimmunization and refractoriness with associated cost burden.

Discussion: In RCTs and RWE studies there was significant heterogeneity in study design and outcome measures. In RWE studies, patients receiving PT may have been at higher risk than those not receiving PT creating potential bias. There were limited data on humanistic and societal burden.

Conclusion: Although PTs are used widely for increasing PC in TCP, it is important to understand the limitations of PTs, and to explore the use of alternative treatment options where available.

KEYWORDS:

• Thrombocytopenia
• platelet count
• platelet transfusion
• thrombopoietin (receptor agonist[s])
• chronic liver disease
• transfusion reaction
• immune thrombocytopenia
• health care costs

Acknowledgements

Medical writing support was provided by Insight Medical Writing, Kidlington, UK (Sarah Germain).

Disclosure statement

AN reports research support from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Octapharma and Rigel and consulting for Amgen, Angle, Argenx, Dova, GlaxoSmithKline, Novartis, ONO Pharmaceutical, Rigel, Shionogi and UCB Biosciences. HL reports grants from Novartis, grants and personal fees from Rigel, personal fees from Dova, grants and personal fees from Argenx, and grants and personal fees from Syntimmune (now Alexion), all outside the submitted work. He also reports previous consulting for Dova on the use of avatrombopag for ITP. MP-R reports personal fees from Shionogi, outside the submitted work. AT reports grants from Shionogi, Kyowa Hakko Kirin, Chugai Pharmaceutical, Zenyaku Kogyo, and the Ministry of Health, Labour and Welfare of Japan, all during the conduct of the study. He also reports grants from the Ministry of Education, Culture, Sports and Technology of Japan, Astellas Pharma, Yamada Bee Farm, and Pfizer, all outside the submitted work. RT reports personal fees of a consultation fee from Shionogi and lecturer fees from Shionogi, Eisai, MSD, Gilead Sciences, Fujifilm Wako and AbbVie, all outside the submitted work. ZY reports being a consultant for Gilead Sciences, Intercept, Bristol-Myers Squibb, Novo Nordisk, Viking, TERNS, Shionogi and AbbVie, all outside the submitted work. RB is an employee of Shionogi. AJ, JL and VT are employees of Creativ-Ceutical.

Availability of data and material

The datasets generated and analyzed during this study are available from the corresponding author on reasonable request.

Notes on contributors

Adrian Newland is Professor of Hematology at Barts NHS Trust, UK. He is ex-Chair of the UK National Blood Transfusion Committee and currently chairs the DMC for NHS Blood and Transplant. He has clinical and research interests in TCP and has been Principal Investigator on many treatment studies and has published extensively on the condition.

Roy Bentley MSc, PhD, is an employee of Shionogi with an interest in health economics and outcomes research, patient-reported outcomes and healthcare policy.

Anna Jakubowska received a PhD in Pharmaceutical Sciences from Jagiellonian University and is an employee of Creativ-Ceutical with experience in the preparation of systematic reviews and health economics and outcomes research.

Howard Liebman is the Donald I Feinstein Professor of Hematology and director of the Diagnostic Hematology group of the Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, USA. His research and publications have centered upon disorders of hemostasis and thrombosis, with a particular interest in platelet disorders and immune TCP.

Joanna Lorens is an employee of Creativ-Ceutical with experience in the preparation of systematic reviews.

Markus Peck-Radosavljevic is Professor of Medicine and Chairman at the Department of Gastroenterology & Hepatology, Endocrinology, Rheumatology and Nephrology at Klinikum Klagenfurt in Klagenfurt, Austria. He began his research in liver disease in the field of TCP in portal hypertension in 1994 and has been working on the role of TPO in advanced stage liver disease for many years, including his role as one of the lead-investigators in the L-PLUS-2 trial. He has also been running a translational lab testing novel approaches to the treatment of portal hypertension and hepatocellular carcinoma (HCC) for many years, while working at the Medical University of Vienna. Since January 2016, he has taken over as Chair of Internal Medicine and Gastroenterology in Klagenfurt, which also includes the Endocrinology, the Rheumatology, the Nephrology (including Hemodialysis) and the Emergency Medicine service. He has set up a new Clinical trials study unit there and is running a broad range of clinical trials in various different indications, including HCC, cholestatic liver diseases and non-alcoholic steatohepatitis.

Vanessa Taieb studied at the Ecole Nationale de la Statistique et de l’Analyse de l’Information and is an employee of Creativ-Ceutical with experience in the preparation of systematic reviews and health economics and outcomes research.

Akiyoshi Takami is Professor of Hematology, Department of Internal Medicine, Aichi Medical University, Japan; Executive director for the Japanese Society for Laboratory Hematology; Supervisor for the Japan Society for Hematopoietic Cell Transplantation; and Chairperson for the Subcommittee on the Guideline for the use of PT preparation of the Japan Society of Transfusion Medicine and Therapy.

Ryosuke Tateishi has worked in the HCC field since 1998 and has served on two guideline committees: Japanese Clinical Practice Guideline for liver cancer and Asian Conference on Tumor Ablation Guideline.

Zobair M. Younossi is Chairman of Medicine and Outcomes Researcher with extensive experience in all types of health services research, including systematic reviews. He is extensively published with a Scopus h-index of 81.

ORCID

Markus Peck-Radosavljevic http://orcid.org/0000-0002-0597-2728

Vanessa Taieb http://orcid.org/0000-0003-0655-8630

Akiyoshi Takami http://orcid.org/0000-0002-1822-9976