Treatment of Critical Bleeds in Patients With Immune Thrombocytopenia: A Systematic Review

Saifur R Chowdhury^{1

2}, Emily Sirotich^{1

2}, Gordon Guyatt^{2

3

4}, Daya Gill¹, Dimpy Modi^{1

3}, Laura M Venier¹, Syed Mahamad^{1

3}, Mahmudur Rahman Chowdhury⁵, Kerolos Eisa¹, Carolyn E Beck⁶, Vicky R Breakey⁷, Kerstin de Wit^{8

9}, Stephen Porter^{10

11}, Kathryn E Webert^{12

13}, Adam Cuker^{14

15}, Clare O'Connor¹⁶, Jennifer MacWhirter -DiRaimo¹⁷, Justin W Yan¹⁸, Charles Manski¹⁹, John G Kelton^{1

3}, Matthew Kang²⁰, Gail Strachan¹⁷, Ziauddin Hassan²¹, Barbara Pruitt¹⁷, Menaka Pai^{1

3}, Rachael F Grace²², Dale Paynter¹⁷, Jay Charness¹⁷, Nichola Cooper²³, Steven Fein²⁴, Arnav Agarwal^{2

3}, Hasmik Nazaryan¹, Ishaq Siddiqui¹⁶, Russell Leong^{16

25}, Sushmitha Pallapothu^{2

26}, Aaron Wen¹, Emily Xu¹, Bonnie Liu¹, Amirmohammad Shafiee¹, Preksha Rathod¹, Henry Kwon²⁷, Jared Dookie¹, Dena Zeraatkar^{2

28}, Lehana Thabane^{2

29

30}, Rachel Couban²⁸, Donald M Arnold^{1

3}

Affiliations

¹ Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Canada.
² Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
³ Department of Medicine, McMaster University, Hamilton, Canada.
⁴ MAGIC Evidence Ecosystem Foundation, Oslo, Norway.
⁵ Department of Public Health, North South University, Dhaka, Bangladesh.
⁶ Division of Paediatric Medicine, Department of Paediatrics, the Hospital for Sick Children, University of Toronto, Toronto, Canada.
⁷ Division of Pediatric Hematology/Oncology, Department of Pediatrics, McMaster University, Hamilton, Canada.
⁸ Department of Emergency Medicine, Queen's University, Kingston, Canada.
⁹ Division of Emergency Medicine, Department of Medicine, McMaster University, Hamilton, Canada.
¹⁰ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹¹ Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹² Canadian Blood Services, Ancaster, Canada.
¹³ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
¹⁴ Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁵ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁶ Faculty of Health Sciences, McMaster University, Hamilton, Canada.
¹⁷ Platelet Disorder Support Association (PDSA), Cleveland, Ohio, USA.
¹⁸ Lawson Health Research Institute, London Health Sciences Centre, Western University, London, Canada.
¹⁹ Northwestern University, Evanston, Illinois, USA.
²⁰ Joseph Brant Hospital, Burlington, Canada.
²¹ Saskatchewan Health Authority, Saskatoon, Canada.
²² Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA.
²³ Department of Inflammation and Immunity, Imperial College London, London, UK.
²⁴ Heme on Call, Telemedicine-Based Hematology Practice, Miami, Florida, USA.
²⁵ Faculty of Medicine, University of Ottawa, Ottawa, Canada.
²⁶ OrthoEvidence, Burlington, Canada.
²⁷ Department of Surgery, Henry Ford Health, Detroit, Michigan, USA.
²⁸ Department of Anesthesia, McMaster University, Hamilton, Canada.
²⁹ Division of Critical Care, St. Joseph's Healthcare Hamilton, Hamilton, Canada.
³⁰ Biostatistics Unit, St. Joseph's Healthcare Hamilton, Hamilton, Canada.

PMID: 39552264
PMCID: PMC11798764
DOI: 10.1111/ejh.14351

Treatment of Critical Bleeds in Patients With Immune Thrombocytopenia: A Systematic Review

Saifur R Chowdhury et al. Eur J Haematol. 2025 Mar.

. 2025 Mar;114(3):458-468.

doi: 10.1111/ejh.14351. Epub 2024 Nov 18.

Authors

Affiliations

¹ Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Canada.
² Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
³ Department of Medicine, McMaster University, Hamilton, Canada.
⁴ MAGIC Evidence Ecosystem Foundation, Oslo, Norway.
⁵ Department of Public Health, North South University, Dhaka, Bangladesh.
⁶ Division of Paediatric Medicine, Department of Paediatrics, the Hospital for Sick Children, University of Toronto, Toronto, Canada.
⁷ Division of Pediatric Hematology/Oncology, Department of Pediatrics, McMaster University, Hamilton, Canada.
⁸ Department of Emergency Medicine, Queen's University, Kingston, Canada.
⁹ Division of Emergency Medicine, Department of Medicine, McMaster University, Hamilton, Canada.
¹⁰ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹¹ Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹² Canadian Blood Services, Ancaster, Canada.
¹³ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
¹⁴ Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁵ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁶ Faculty of Health Sciences, McMaster University, Hamilton, Canada.
¹⁷ Platelet Disorder Support Association (PDSA), Cleveland, Ohio, USA.
¹⁸ Lawson Health Research Institute, London Health Sciences Centre, Western University, London, Canada.
¹⁹ Northwestern University, Evanston, Illinois, USA.
²⁰ Joseph Brant Hospital, Burlington, Canada.
²¹ Saskatchewan Health Authority, Saskatoon, Canada.
²² Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA.
²³ Department of Inflammation and Immunity, Imperial College London, London, UK.
²⁴ Heme on Call, Telemedicine-Based Hematology Practice, Miami, Florida, USA.
²⁵ Faculty of Medicine, University of Ottawa, Ottawa, Canada.
²⁶ OrthoEvidence, Burlington, Canada.
²⁷ Department of Surgery, Henry Ford Health, Detroit, Michigan, USA.
²⁸ Department of Anesthesia, McMaster University, Hamilton, Canada.
²⁹ Division of Critical Care, St. Joseph's Healthcare Hamilton, Hamilton, Canada.
³⁰ Biostatistics Unit, St. Joseph's Healthcare Hamilton, Hamilton, Canada.

PMID: 39552264
PMCID: PMC11798764
DOI: 10.1111/ejh.14351

Abstract

Objectives: Evidence-based protocols for managing bleeding emergencies in patients with immune thrombocytopenia (ITP) are lacking. We conducted a systematic review of treatments for critical bleeding in patients with ITP.

Methods: We included all study designs and extracted data in aggregate or individually for patients who received one or more interventions and for whom any of the following outcomes were reported: platelet count response, bleeding, disability, or death.

Results: We identified 49 eligible studies reporting 112 critical bleed patients with ITP, including 66 children (median age, 10 years), 36 adults (median age, 41.5 years), and 10 patients with unreported age. Patients received corticosteroids (n = 67), IVIG (n = 49), platelet transfusions (n = 41), TPO-RAs (n = 17), and splenectomy (n = 28) either alone or in combination. Studies reported 29 different treatment combinations, the 5 most common were corticosteroids, platelet transfusion and splenectomy (n = 13), corticosteroids and IVIG (n = 13), or splenectomy alone (n = 13); IVIG alone (n = 11); and corticosteroids, IVIG and TPO-RA (n = 8). Mortality among patients with critical bleeds in ITP was 30.6% for adults and 19.7% for children.

Conclusions: The effects of individual treatments on patient outcomes were uncertain due to very low-quality evidence. There is a need for a standardized approach to the treatment of ITP critical bleeds.

Systematic review registration: CRD42020161206.

Keywords: critical bleeding; emergency management; immune thrombocytopenia; major bleeding; thrombocytopenia.

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Conflict of interest statement

Dr. Pai reports personal fees from Pfizer, personal fees and non‐financial support from Pfizer, outside the submitted work; Dr. Beck reports grants from Canadian Institutes of Health Research, during the conduct of the study; Dr. DiRaimo has not personally received any payment, PDSA received grants and consultancy fees from Novartis, Sobi, Sanofi, Amgen and Argenx but not for anything related to this work/manuscript; Dr. Cuker reports personal fees from Synergy, personal fees from Sanofi, personal fees from Pfizer, personal fees from MingSight, personal fees from UpToDate, outside the submitted work; Dr. Grace reports other from Agios, other from Novartis, other from Sobi, other from Sanofi, outside the submitted work; Dr. Arnold reports grants and personal fees from Rigel, personal fees from Amgen, personal fees from Medison, personal fees from Daiichi Sankyo, personal fees from Sobi, personal fees from Principia, personal fees from Chugai, personal fees from Alpine, personal fees from ArgenX, personal fees from Sanofi, personal fees from UpToDate, outside the submitted work. Other authors declare they have no competing interests.

Figures

**FIGURE 1**
PRISMA flow diagram of selected studies.

See this image and copyright information in PMC

References

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Treatment of Critical Bleeds in Patients With Immune Thrombocytopenia: A Systematic Review

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Treatment of Critical Bleeds in Patients With Immune Thrombocytopenia: A Systematic Review

Authors

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Conflict of interest statement

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