BACKGROUND: Laboratory tests to assess novel oral anticoagulants (NOACs) are under evaluation. Routine monitoring is unnecessary, but under special circumstances bioactivity assessment becomes crucial. We analyzed the effects of NOACs on coagulation tests and the availability of specific assays at different laboratories.

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BACKGROUND: Uncontrollable bleeding is the leading cause of death in traumatically injured patients. The extent to which direct factor Xa inhibitors interfere with the applied resuscitation measures is presently unknown. STUDY DESIGN AND METHODS:In this study, we investigated the effect of the resuscitation fluids saline, albumin, fresh frozen plasma (FFP) and solvent/ detergent (S/D)-treated plasma, fibrinogen concentrate, prothrombin complex concentrate (PCC), and combinations thereof on the hemostatic profile of rivaroxaban-anticoagulated whole blood and plasma. We used rivaroxaban-spiked whole blood and plasma from healthy donors, as well as plasma from patients on rivaroxaban, and mimicked a resuscitation approach in a 50% plasma dilution setting. Thromboelastography, thrombin generation, and fibrin generation clot lysis test were assessed using tissue factor to initiate coagulation and tissue plasminogen activator to induce clot lysis.ABBREVIATIONS: CAT = calibrated automated thrombography; CLT = clot lysis time; FGCLT = fibrin generation clot lysis test; FXa-I = factor Xa inhibitor; MA = maximal amplitude; PCC = prothrombin complex concentrate; TEG = thromboelastography; TF = tissue factor; tPA = tissue plasminogen activator; TXA = tranexamic acid.From the

Factor Xa inhibitors (FXaI) apixaban and rivaroxaban are used for thromboprophylaxis after major elective orthopaedic surgery. Because few patient sample studies exist, we postoperatively assessed patients undergoing unilateral total hip arthroplasty, including 22 treated with apixaban (2.5 mg BID) and 20 treated with rivaroxaban (10 mg OD). We collected blood samples before and 3 h after drug intake at 4 time points, preoperatively, as well as on day 1, week 1 (day 2-8) and day 28 post-operation. APTT and PT were immediately analysed. Calibrated anti-FXa activity, Russel's Viper Venom Time (RVVT) and thrombin generation (TG; Calibrated Automated Thrombogram) captured the effects of FXaI on coagulation and TG. APTT and PT remained within the reference interval throughout, and did not correlate with FXaI levels (PT R = 0.44, APTT R = 0.07). Mean apixaban concentration at the peak varied by eightfold (19-153 ng/mL), but rivaroxaban only by 1.5-fold (111-183 ng/mL). Rivaroxaban, but not apixaban prolonged RVVT at peak levels. Both FXaIs had a prolonged lag time of TG (p < 0.001). Rivaroxaban decreased ETP peak at all time points and reached a minimum at day 28 (540 nM/min at rivaroxaban 184 ng/mL, p < 0.001), while rivaroxaban trough levels were low and ETP values normal. However, with apixaban, after an initial decrease, ETP did not differ between peak and trough levels until decreasing on day 28 at peak (990 nM/min at apixaban 112 ng/mL, p = 0.005). In conclusion, due to different dosing and pharmacology rivaroxaban and apixaban distinctly inhibited TG under postoperative conditions.

Anticoagulation therapy has been undergoing a transition during the last decade with the progressive availability of direct oral anticoagulants (DOACs). While DOACs are increasingly used in common indications for anticoagulation, including non-valvular atrial fibrillation (AF), deep vein thrombosis (DVT) and pulmonary embolism (PE), traditional anticoagulants, either warfarin or heparins, remain the primary choice for patients with cardiac valvular replacement, severe thrombophilia, pediatric, pregnant and many cancer patients. Laboratory monitoring of warfarin and heparins are well established, while under specific emergency conditions DOACs require specific assays, the availability of which may be limited.Finland benefits from centralized laboratory networks, offering harmonized services throughout our rather sparsely populated country. Specific assays for all DOACs are available 24/7 in the core laboratory (Southern Finland). Interaction, collaboration and continuous education between clinic and laboratory is increasingly needed, under the era of rapid change of traditions in anticoagulation management.