Correlation of Plasma Coagulation Parameters With Thromboprophylaxis, Patient Characteristics, and Outcome in the MEDENOX Study

Abstract

Context.—Plasma anti-Xa and anti-IIa activities correlate with the dose of low-molecular-weight heparin, and D-dimer and thrombin-antithrombin complexes are markers of procoagulant activity. Objective.—To investigate the relationship between plasma coagulation parameters and patient characteristics, including renal function, thromboprophylaxis, and incidence of venous thromboembolism (VTE) in the MEDENOX study population. Design.—Controlled, multicenter, double-blind, randomized study. Patients.—Two hundred twenty-four acutely ill medical patients. Interventions.—Either 20 or 40 mg of enoxaparin administered subcutaneously or a placebo once daily for 10 (±4) days. Main Outcome Measures.—VTE and plasma anti-Xa and anti-IIa activities, D-dimer, and thrombin-antithrombin levels in blood collected before prophylaxis was given (day 0) and after the last injection of the study drug. Results and Conclusions.—Anti-Xa activity correlated with the dose of enoxaparin. In patients with mild or moderate renal impairment, there was no significant relationship between anti-Xa activity and the creatinine clearance rate. D-dimer concentrations were lower at day 10 (±4) in the 40-mg group, which had a 63% lower VTE incidence, than at day 0. No venographically confirmed thromboses were found in patients with a normal D-dimer concentration (<0.5 μg/mL [0.5 mg/L]). D-dimer levels were higher in patients with VTE than in those without VTE, but no predictive value could be demonstrated for individual patients.

Targeting Coagulase Activity in Staphylococcus aureus Bacteraemia: A Randomized Controlled Single-Centre Trial of Staphylothrombin Inhibition

“…We did not observe accumulation or overanticoagulation in these patients. 26,27 We have previously described that the inhibition constant K i of dabigatran for staphylothrombin is in the low nanomolar range and similar to the K i of dabigatran for thrombin. 16 The obtained concentrations of dabigatran indeed efficiently inhibited staphylothrombin in vitro (►Fig.…”

“…With an estimated D-dimer decline of 1,000 ng/ mL in the DTI-group versus 500 ng/mL in the control group, a sample size of 2 Â 50 patients has 80% power to detect such difference (α ¼ 0.10, two-sided). 25,26 Statistical analysis was done in an intention-to-treat model (retaining all participants in their originally assigned group), as well as per protocol (defined as patients that received at least 80% of scheduled doses of DTI from randomization to day 4; compared with control patients). We used GraphPad Prism (version 5.0b, GraphPad Software) and utilized appropriate tests to compare continuous variables between groups (unpaired t-test or Mann-Whitney test, depending on normal distribution, always two-sided) and Fisher's exact test for dichotomous variables.…”

“…Overall, duration of antibiotic therapy was similar in both treatment groups, with a median (IQR) duration of 16 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) days in the enoxaparin group, versus 18 (12-30) days in the DTI group. Sixteen patients in the enoxaparin group, and 21 patients in the DTI group, received extended treatment.…”

Anti-Xa Activity of Enoxaparin for Prevention of Venous Thromboembolism in Severe Nephrotic Syndrome—A Single Center Prospective Study

“…Our results support the hypothesis of decreased drug activity in this group. The disproportion between anti-FXa in our NS-FD group to non-proteinuric patients is even higher if compared to patients after orthopedic surgery, with acute medical non-surgical conditions or in healthy volunteers (reported anti-FXa ranged from 0.41 to 0.59 IU/mL) than to our C-FD group (mean anti-FXa 0.33 IU/mL) [ 24 , 25 , 26 ].…”

Weight-adjusted dosing of tinzaparin for thromboprophylaxis in obese medical patients

“…This confirms the data of Franco et al., [ 59 ] who reported elevated D-dimer in obese patients in correlation to the waist-to-hip ratio. Elevated D-dimer have been reported to predict VTE in acutely ill medical patients [ [60] , [61] , [62] ]. In the MEDENOX trial that included nonobese patients, 40-mg of enoxaparin but not 20-mg of enoxaparin or placebo resulted in a small but significant reduction in the elevated baseline D-dimer activity after 10 days [ 62 ].…”