Coagulation parameters in patients receiving dabigatran etexilate or rivaroxaban: two observational studies in patients undergoing total hip or total knee replacement.

Introduction: Dabigatran and rivaroxaban have recently been added to the armamentarium for thromboprophylaxis in orthopedic surgery. Although this is their first licensed indication, others will soon follow. Owing to their claimed predictable anticoagulant response that dispenses with the need for monitoring coagulation, their effects are poorly described in routine cases. However, interpreting blood coagulation results and evaluating whether a treatment is properly targeted in the case of untoward incidents will become a common concern for clinicians.

Methods: Eighty patients undergoing total hip or knee replacement were included in two studies. Forty of them received dabigatran (study 1) and 40 rivaroxaban (study 2). Blood samples (n = 176 and 166) were taken preoperatively and twice a week from the first postoperative day.

Results: Dabigatran increased aPTTr about two-fold and PT about 1.2-fold, and it was mostly an initiation-phase modulator of thrombin generation. Mean circulating concentrations as measured by a diluted thrombin time were 105 ± 85 ng/mL at T(max) in samples from patients receiving the full dosing. They depended significantly on renal function, body weight and gender. Rivaroxaban increased aPTTr and PTr around 1.5 fold and modified the initiation and amplification phases of thrombin generation, with a lowered and prolonged thrombin burst. Mean circulating concentrations as measured by an antiXa test were 117 ± 78 ng/mL at T(max). With both drugs, routine coagulation tests, thrombin generation curves and functionally determined concentrations exhibited high interindividual variability.

Conclusion: Routine coagulation tests are altered in patients receiving dabigatran or rivaroxaban, but their alterations poorly reflect the circulating concentrations as determined by functional approaches.