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Original Research: Critical Care |

Thrombocytopenia in Critically Ill Patients Receiving ThromboprophylaxisThrombocytopenia in the Critically Ill: Frequency, Risk Factors, and Outcomes

David R. Williamson, BPharm, MSc; Martin Albert, MD; Diane Heels-Ansdell, MSc; Donald M. Arnold, MD; François Lauzier, MD; Ryan Zarychanski, MD; Mark Crowther, MD; Theodore E. Warkentin, MD; Peter Dodek, MD; John Cade, MD, FCCP; Olivier Lesur, MD, PhD; Wendy Lim, MD; Robert Fowler, MD; Francois Lamontagne, MD; Stephan Langevin, MD; Andreas Freitag, MD, FCCP; John Muscedere, MD; Jan O. Friedrich, MD, DPhil; William Geerts, MD; Lisa Burry, PharmD; Jamal Alhashemi, MD, FCCP; Deborah Cook, MD; and the PROTECT collaborators, the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group
Author and Funding Information

From Hôpital du Sacré-Coeur de Montréal (Mr Williamson and Dr Albert), Montreal, QC, Canada; the Department of Pharmacy (Mr Williamson) and the Department of Medicine (Dr Albert), Université de Montréal, Montreal, QC, Canada; Canadian Blood Services (Dr Arnold), Ottawa, ON, Canada; Centre de recherche du CHU de Québec and Université Laval (Drs Lauzier and Langevin), Montreal, QC, Canada; Centre Hospitalier Universitaire de Sherbrooke and Université de Sherbrooke (Drs Lesur and Lamontagne), Sherbrooke, QC, Canada; Cancercare Manitoba and University of Manitoba (Dr Zarychanski), Winnipeg, MB, Canada; St.Paul’s Hospital and University of British Columbia (Dr Dodek), Vancouver, BC, Canada; the Department of Clinical Epidemiology and Biostatistics (Ms Heels-Ansdell and Drs Arnold, Crowther, Warkentin, and Cook), the Department of Medicine (Drs Warkentin, Lim, Freitag, and Cook), and the Department of Pathology and Molecular Medicine (Dr Warkentin), McMaster University, Hamilton, ON, Canada; the Department of Medicine (Drs Fowler, Friedrich, and Geerts), University of Toronto, Toronto, ON, Canada; Sunnybrook Health Sciences Center (Drs Fowler and Geerts), Toronto, ON, Canada; St. Michael’s Hospital (Dr Friedrich), Toronto, ON, Canada; Mount Sinai Hospital (Dr Burry), Toronto, ON, Canada; Kingston General Hospital and Queens University (Dr Muscedere), Kingston, ON, Canada; Royal Melbourne Hospital (Dr Cade), Melbourne, VIC, Australia; and King Abdulaziz University (Dr Alhashemi), Jeddah, Saudi Arabia.

Correspondence to: David R. Williamson, BPharm, MSc, Hôpital du Sacré-Coeur de Montréal, Pharmacy Department, 5400 Gouin W, Montreal, QC, H4J 1C5, Canada; e-mail: david.williamson@umontreal.ca


*A complete list of PROTECT collaborators is located in e-Appendix 1.

Funding/Support: The original trial was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, and the Australian and New Zealand College of Anesthetists Research Foundation.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(4):1207-1215. doi:10.1378/chest.13-0121
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Background:  Thrombocytopenia is the most common hemostatic disorder in critically ill patients. The objective of this study was to describe the incidence, risk factors, and outcomes of thrombocytopenia in patients admitted to medical-surgical ICUs.

Methods:  Three thousand seven hundred forty-six patients in 67 centers were enrolled in a randomized trial in which unfractionated heparin was compared with low-molecular-weight heparin (LMWH) for thromboprophylaxis. Patients who had baseline platelet counts < 75 × 109/L or severe coagulopathy at screening were excluded. We analyzed the risk of developing mild (100-149 × 109/L), moderate (50-99 × 109/L), and severe (< 50 × 109/L) thrombocytopenia during an ICU stay. We also assessed independent and time-varying predictors of thrombocytopenia and the effect of thrombocytopenia on major bleeding, transfusions, and death.

Results:  The incidences of mild, moderate, and severe thrombocytopenia were 15.3%, 5.1%, and 1.6%, respectively. The predictors of each category of thrombocytopenia were APACHE (Acute Physiology and Chronic Health Evaluation) II score, use of inotropes or vasopressors, and renal replacement therapy. The risk of moderate thrombocytopenia was lower in patients who received LMWH thromboprophylaxis but higher in surgical patients and in patients who had liver disease. Each category of thrombocytopenia was associated with subsequent bleeding and transfusions. Moderate and severe thrombocytopenia were associated with increased ICU and hospital mortality.

Conclusion:  A high severity of illness, prior surgery, use of inotropes or vasopressors, renal replacement therapy, and liver dysfunction are associated with a higher risk of thrombocytopenia developing in the ICU, whereas LMWH thromboprophylaxis is associated with a lower risk. Patients who develop thrombocytopenia in the ICU are more likely to bleed, receive transfusions, and die.

Trial registry:  ClinicalTrials.gov; No.: NCT00182143; URL: www.clinicaltrials.gov

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