Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis.
OBJECTIVE
Bleeding frequently complicates critical illness and may have serious consequences. Our objectives are to describe the predictors of major bleeding and the association between bleeding and mortality in medical-surgical critically ill patients receiving heparin thromboprophylaxis.


METHODS
We prospectively studied patients from 67 intensive care units and six countries enrolled in a thromboprophylaxis trial (NCT00182143) comparing dalteparin with unfractionated heparin. Patients with trauma, orthopedic surgery or neurosurgery were excluded. Trained research coordinators used a validated tool to document bleeding, which underwent duplicate independent blinded adjudication. Major bleeding was defined as hypovolemic shock, bleeding into critical sites, requiring an invasive intervention or transfusion of at least two units of red blood cells, or associated with hypotension or tachycardia in the absence of other causes. Adjusted Cox proportional hazard regression analysis was used to identify major bleeding predictors and the association between bleeding and mortality.


RESULTS
Among 3,746 patients, bleeding occurred in 208 [5.6 %, 95 % confidence interval (CI) 4.9-6.3 %]. Time-dependent predictors were prolonged activated partial thromboplastin time [hazard ratio (HR) 1.10, 1.05-1.14 per 10 s increase], lower platelet count (HR 1.16, 1.09-1.24 per 50 × 10(9)/L decrease), therapeutic heparin (HR 3.26, 1.72-6.17), antiplatelet agents (HR 1.38, 1.02-1.88), renal replacement therapy (HR 1.75, 1.20-2.56), and recent surgery (HR 1.64, 1.01-2.65). Type of pharmacologic thromboprophylaxis was not associated with bleeding. Patients with bleeding had a higher risk of in-hospital death (HR 2.09, 1.69-2.57).


CONCLUSIONS
As major bleeding has modifiable risk factors and is associated with in-hospital mortality, strategies to mitigate these factors should be evaluated in critically ill patients.
Division of Critical Care, Departments of Medicine and of Anesthesiology, Centre de recherche du CHU de Québec, Axe Santé des populations et pratiques optimales en santé, Université Laval, 1401, 18e Rue, Québec, QC, G1J 1Z4, Canada, francois.lauzier@med.ulaval.ca.
François
F
Lauzier
Donald M
DM
Arnold
Christian
C
Rabbat
Diane
D
Heels-Ansdell
Ryan
R
Zarychanski
Peter
P
Dodek
Betty Jean
BJ
Ashley
Martin
M
Albert
Kosar
K
Khwaja
Marlies
M
Ostermann
Yoanna
Y
Skrobik
Robert
R
Fowler
Lauralyn
L
McIntyre
Joseph L
JL
Nates
Tim
T
Karachi
Renato D
RD
Lopes
Nicole
N
Zytaruk
Simon
S
Finfer
Mark
M
Crowther
Deborah
D
Cook
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D016638:Critical Illness / Q000401:mortality / Q000628:therapy*; D017985:Dalteparin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality; D006493:Heparin / Q000009:adverse effects* / Q000627:therapeutic use; D017052:Hospital Mortality; D006801:Humans; D015994:Incidence; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000517:prevention & control*; D016896:Treatment Outcome
D000925:Anticoagulants; D006493:Heparin; D017985:Dalteparin