Results of rotational thromboelastometry, coagulation activation markers and thrombin generation assays in orthopedic patients during thromboprophylaxis with rivaroxaban and enoxaparin: a prospective cohort study.
BACKGROUND
A prospective observational study was conducted in two clinical cohorts of patients to compare the effect of enoxaparin and rivaroxaban on rotational thromboelastometry (ROTEM), coagulation activation markers and thrombin generation.


METHODS
A total of 188 consecutive patients scheduled for major orthopedic surgery receiving 40-mg enoxaparin subcutaneously or 10-mg rivaroxaban orally were evaluated. Blood samples were taken before induction of anesthesia and on day 4 after surgery [postoperative day 4 (pod 4)]. The extrinsically (EXTEM) and the intrinsically (INTEM) activated ROTEM assay, antithrombin, prothrombin fragments (F1 + 2), thrombin-antithrombin complex (TAT) and D-dimers were measured, and the thrombodynamic ratio (TDR) was calculated. Thrombin generation was determined using calibrated automated thrombography. To compare the groups, changes (Δ) in baseline versus pod 4 were calculated.


RESULTS
EXTEM clotting time (CT) increased more with rivaroxaban than with enoxaparin; values above the reference range were observed (median ΔEXTEM-CT 15 vs. 5 s, P ≤ 0.0001). The increase in INTEM-CT (values remained within the normal ranges) was slight with enoxaparin and significant with rivaroxaban; ΔINTEM-CT was comparable. EXTEM-TDR, unchanged with rivaroxaban, increased significantly with enoxaparin, whereas ΔINTEM-TDR was comparable. ΔAT, ΔF1 + 2 and ΔTAT were significantly lower in the rivaroxaban group. Endogenous thrombin potential (ETP), unchanged with rivaroxaban, decreased significantly with enoxaparin; the maximal rising slope (mean velocity rate index) decreased more with rivaroxaban.


CONCLUSIONS
Data show that prolonged CT in the extrinsic ROTEM and thrombin generation assays reflecting initiation and propagation of thrombin may be useful for detecting treatment with rivaroxaban. The significance of observed differences in markers of coagulation needs to be investigated further.
aDepartment of Anaesthesiology and Intensive Care Medicine bDepartment of Orthopedics cDepartment of Medical Statistics, Informatics and Health Economics dDepartment of Pediatrics and Adolescent Medicine, Innsbruck Medical University, Innsbruck, Austria.
Elgar
E
Oswald
Corinna
C
Velik-Salchner
Petra
P
Innerhofer
Helmuth
H
Tauber
Thomas
T
Auckenthaler
Hanno
H
Ulmer
Werner
W
Streif
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D015331:Cohort Studies; D017984:Enoxaparin / Q000008:administration & dosage*; D065427:Factor Xa Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage*; D019637:Orthopedic Procedures / Q000379:methods*; D011446:Prospective Studies; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage*; D013916:Thrombelastography; D013917:Thrombin / Q000096:biosynthesis*; D054556:Venous Thromboembolism / Q000097:blood / Q000517:prevention & control
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban; D013917:Thrombin