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David R. Williamson, BPharm, MSc; Martin Albert, MD; Diane Heels-Ansdell, MSc; Deborah Cook, MD; For the PROTECT Collaborators
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From the Hôpital du Sacré-Coeur de Montréal (Mr Williamson and Dr Albert); Faculté de Pharmacie (Mr Williamson), and Faculté de Médecine (Dr Albert), Université de Montréal; and the Departments of Clinical Epidemiology and Biostatistics (Ms Heels-Ansdell and Dr Cook) and Department of Medicine (Dr Cook), McMaster University.

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


Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Mr Williamson has received speaker honoraria from Boeringher-Ingleheim GmbH and Pfizer, Inc. He is a recipient of a doctoral training award for applicants with a professional degree from the Fonds de la recherché du Québec-Santé (FRQ-S). Dr Cook is a research chair of the CIHR. Ms Heels-Ansdell has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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


Chest. 2013;144(6):1979-1980. doi:10.1378/chest.13-2111
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To the Editor:

We thank Dr Thachil for his comments. Although the safety of anticoagulant thromboprophylaxis in patients developing thrombocytopenia was not the subject of our study,1 we agree that this issue is important. In the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT), patients with thrombocytopenia on enrollment (platelets < 75 × 109/L) were excluded.2 If platelet count decreased to < 50 × 109/L in the ICU in enrolled patients, the study drug (either unfractionated heparin or dalteparin) was withheld and restarted at the clinician’s discretion. Consequently, a small proportion of the study population did receive anticoagulant thromboprophylaxis for some of the days during which they were thrombocytopenic (41.5% of ICU days during which platelet count was < 50 × 109/L). However, “indication bias” precludes strong inferences about the safety of anticoagulant thromboprophylaxis in the setting of severe thrombocytopenia in that patients perceived to be at lower risk of bleeding would, on balance, be the patients who were prescribed thromboprophylaxis.

In our analysis, each thrombocytopenia category (mild, moderate, and severe) was associated with an increased risk of major bleeding (adjusted hazard ratio [aHR], 1.96 and 95% CI, 1.38-2.78; aHR, 3.52 and 95% CI, 2.47-5.04; and aHR, 3.54 and 95% CI, 2.09-5.99, respectively).1 In a detailed analysis using Cox modeling to examine baseline and time-dependent risk factors for major bleeding, we considered platelet count; unfractionated heparin and dalteparin, as well as therapeutic heparin, acetylsalicylic acid, or clopidogrel; activated protein C; international normalized ratio; activated partial thromboplastin time; surgical procedures; and stress ulcer prophylaxis. We did find that platelet count was an independent risk factor for major bleeding (aHR, 1.16; 95% CI, 1.09-1.24), but that type of heparin was not (dalteparin aHR, 1.16 and 95% CI, 0.78-1.73; and unfractionated heparin aHR, 0.93 and 95% CI, 0.62-1.39).3 Given the dynamic thrombotic and bleeding risks in the ICU setting, we agree that future studies should evaluate the benefits and risks of maintaining or withholding thromboprophylaxis in critically ill patients with severe thrombocytopenia.

References

Williamson DR, Albert M, Heels-Ansdell D, et al. Thrombocytopenia in critically ill patients receiving thromboprophylaxis: frequency, risk factors, and outcomes Chest. 2013;144(4):1207-1215. [CrossRef] [PubMed]
 
PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011;364(14):1305-1314. [CrossRef] [PubMed]
 
Lauzier F, Arnold DM, Rabbat C, et al. Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis [published online ahead of print August 14, 2013]. Intensive Care Med. doi:10.1007/s00134-013-3044-3.
 

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References

Williamson DR, Albert M, Heels-Ansdell D, et al. Thrombocytopenia in critically ill patients receiving thromboprophylaxis: frequency, risk factors, and outcomes Chest. 2013;144(4):1207-1215. [CrossRef] [PubMed]
 
PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011;364(14):1305-1314. [CrossRef] [PubMed]
 
Lauzier F, Arnold DM, Rabbat C, et al. Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis [published online ahead of print August 14, 2013]. Intensive Care Med. doi:10.1007/s00134-013-3044-3.
 
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