title: Venous thromboembolism and bleeding in critically ill patients with severe renal insufficiency receiving dalteparin thromboprophylaxis: prevalence, incidence and risk factors.
abstract: BACKGROUND
  Critically ill patients with renal insufficiency are predisposed to both deep vein thrombosis (DVT) and bleeding. The objective of the present study was to evaluate the prevalence, incidence and predictors of DVT and the incidence of bleeding in intensive care unit (ICU) patients with estimated creatinine clearance <30 ml/min.
  
  
  METHODS
  In a multicenter, open-label, prospective cohort study of critically ill patients with severe acute or chronic renal insufficiency or dialysis receiving subcutaneous dalteparin 5,000 IU once daily, we estimated the prevalence of proximal DVT by screening compression venous ultrasound of the lower limbs within 48 hours of ICU admission. DVT incidence was assessed on twice-weekly ultrasound testing. We estimated the incidence of major and minor bleeding by daily clinical assessments. We used Cox proportional hazards regression to identify independent predictors of both DVT and major bleeding.
  
  
  RESULTS
  Of 156 patients with a mean (standard deviation) creatinine clearance of 18.9 (6.5) ml/min, 18 had DVT or pulmonary embolism within 48 hours of ICU admission, died or were discharged before ultrasound testing - leaving 138 evaluable patients who received at least one dose of dalteparin. The median duration of dalteparin administration was 7 days (interquartile range, 4 to 12 days). DVT developed in seven patients (5.1%; 95% confidence interval, 2.5 to 10.1). The only independent risk factor for DVT was an elevated baseline Acute Physiology and Chronic Health Evaluation II score (hazard ratio for 10-point increase, 2.25; 95% confidence interval, 1.03 to 4.91). Major bleeding developed in 10 patients (7.2%; 95% confidence interval, 4.0 to 12.8), all with trough anti-activated factor X levels </= 0.18 IU/ml. Independent risk factors for major bleeding were aspirin use (hazard ratio, 6.30; 95% confidence interval, 1.35 to 29.4) and a high International Normalized Ratio (hazard ratio for 0.5-unit increase, 1.68; 95% confidence interval, 1.07 to 2.66).
  
  
  CONCLUSIONS
  In ICU patients with renal insufficiency, the incidence of DVT and major bleeding are considerable but appear related to patient comorbidities rather than to an inadequate or excessive anticoagulant from thromboprophylaxis with dalteparin.
authors.affiliation: Department of Medicine, 1200 Main Street, McMaster University, Hamilton, Canada. debcook@mcmaster.ca
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
authors.forename: James
authors.initials: J
authors.lastname: Douketis
authors.forename: Maureen
authors.initials: M
authors.lastname: Meade
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
authors.forename: Nicole
authors.initials: N
authors.lastname: Zytaruk
authors.forename: John
authors.initials: J
authors.lastname: Granton
authors.forename: Yoanna
authors.initials: Y
authors.lastname: Skrobik
authors.forename: Martin
authors.initials: M
authors.lastname: Albert
authors.forename: Robert
authors.initials: R
authors.lastname: Fowler
authors.forename: Paul
authors.initials: P
authors.lastname: Hebert
authors.forename: Guiseppe
authors.initials: G
authors.lastname: Pagliarello
authors.forename: Jan
authors.initials: J
authors.lastname: Friedrich
authors.forename: Andreas
authors.initials: A
authors.lastname: Freitag
authors.forename: Tim
authors.initials: T
authors.lastname: Karachi
authors.forename: Christian
authors.initials: C
authors.lastname: Rabbat
authors.forename: Diane
authors.initials: D
authors.lastname: Heels-Ansdell
authors.forename: William
authors.initials: W
authors.lastname: Geerts
authors.forename: Mark
authors.initials: M
authors.lastname: Crowther
mesh_terms: D018806:APACHE; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D016638:Critical Illness; D017985:Dalteparin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D019934:International Normalized Ratio; D007866:Leg / Q000098:blood supply / Q000000981:diagnostic imaging; D008297:Male; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000453:epidemiology / Q000209:etiology*; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000150:complications*; D012307:Risk Factors; D014463:Ultrasonography; D020246:Venous Thrombosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology*
chemical_list: D000925:Anticoagulants; D017985:Dalteparin