title: Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study.
abstract: BACKGROUND
  Deep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have become increasingly used for prophylactic anticoagulation in critically ill patients. In this prospective study, we evaluated the potency of 3,000 IU certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa) levels of 0.1 to 0.3 IU/ml in 62 critically ill patients.
  
  
  METHODS
  AFXa levels were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin, platelet count, serum urea and creatinine concentrations were documented before and 12 and 24 h after injection of certoparin.
  
  
  RESULTS
  Four hours after certoparin injection (n = 32), 28% of patients were within the antithrombotic aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of a severe pulmonary embolism in one study patient, an interim analysis was performed, and the dosage of certoparin was increased to 3,000 IU twice daily. This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and 30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased during the observation period. Low antithrombin concentrations before certoparin were independently correlated with underdosing of certoparin. Patients with aFXa levels <0.1 IU/ml 4 h after certoparin injection required vasopressors more often and had lower serum concentrations of creatinine and urea than patients with antithrombotic aFXa levels.
  
  
  CONCLUSIONS
  Standard dosages of certoparin of 3,000 IU given once or twice daily are ineffective for attaining the recommended aFXa levels of 0.1 to 0.3 IU/ml in critically ill patients. Low antithrombin levels before certoparin administration were independently associated with low aFXa levels. Renal function and vasopressor therapy may further influence the effectiveness of certoparin in ensuring adequate antithrombotic prophylaxis.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Innsbruck Medical University, Innsbruck, Austria. stefan.jochberger@uibk.ac.at
authors.forename: Stefan
authors.initials: S
authors.lastname: Jochberger
authors.forename: Viktoria
authors.initials: V
authors.lastname: Mayr
authors.forename: Günter
authors.initials: G
authors.lastname: Luckner
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Fries
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Mayr
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Friesenecker
authors.forename: Ingo
authors.initials: I
authors.lastname: Lorenz
authors.forename: Walter R
authors.initials: WR
authors.lastname: Hasibeder
authors.forename: Hanno
authors.initials: H
authors.lastname: Ulmer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schobersberger
authors.forename: Martin W
authors.initials: MW
authors.lastname: Dünser
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004812:Epidemiologic Methods; D015951:Factor Xa / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D015951:Factor Xa; C403769:certoparin