title: Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis: a randomized controlled pilot trial.
abstract: BACKGROUND
  The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates.
  
  
  METHODS
  A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations.
  
  
  RESULTS
  A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p < 0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p < 0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency.
  
  
  CONCLUSIONS
  TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway.
  
  
  METHODS
  Therapeutic study, level III.
authors.affiliation: From the Department of Surgery, Division of Trauma and Acute Care Surgery, Trauma Research Institute of Oregon (TRIO) (S.G.L., P.Y.V., G.M.R., J.S.B., N.R.K., S.U., J.D., M.S.), Oregon Health and Science University, Portland, Oregon; and Department of Surgery, University of Miami School of Medicine (E.G.), Miami, Florida.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Louis
authors.forename: Philbert Y
authors.initials: PY
authors.lastname: Van
authors.forename: Gordon M
authors.initials: GM
authors.lastname: Riha
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Barton
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Kunio
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Underwood
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Differding
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rick
authors.forename: Enrique
authors.initials: E
authors.lastname: Ginzburg
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schreiber
mesh_terms: D001777:Blood Coagulation; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000008:administration & dosage*; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods*; D010865:Pilot Projects; D011446:Prospective Studies; D013916:Thrombelastography / Q000379:methods*; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000097:blood / Q000517:prevention & control*
chemical_list: D017984:Enoxaparin; D005343:Fibrinolytic Agents; D015951:Factor Xa