Research into new anticoagulants for preventing and treating thromboembolic disorders has focused on targeting single enzymes in the coagulation cascade, particularly Factor Xa and thrombin, inhibition of which greatly decreases thrombin generation. Based on the results of phase III clinical trials, rivaroxaban, a direct Factor Xa inhibitor, has been approved in many countries for the management of several thromboembolic disorders. Owing to its predictable pharmacokinetic and pharmacodynamic characteristics, fixed-dose regimens are used without the need for routine coagulation monitoring. In situations where assessment of rivaroxaban exposure may be helpful, anti-Factor Xa chromogenic assays (in tandem with standard calibration curves generated with the use of rivaroxaban calibrators and controls) could be used. It is important to note that test results will be affected by the timing of blood sampling after rivaroxaban intake. In addition, the anti-Factor Xa method measures the drug concentration and not the intensity of the drug’s anticoagulant activity, and a higher than expected rivaroxaban plasma level does not necessarily indicate an increased risk of bleeding complications. Therefore, clinicians need to consider test results in relation to the pharmacokinetics of rivaroxaban and other patient risk factors associated with bleeding.

With the introduction of new anticoagulant agents, there is a need for information on which coagulation tests are most suitable. These agents react differently to assays used to monitor older anticoagulant agents because they have alternative modes of action. Therefore, other tests, or modifications of existing tests which are more appropriate for newer agents, are needed. The prothrombin time test (with conversion to the international normalized ratio) is usually used to monitor warfarin. However, conversion to the international normalized ratio is not appropriate for measuring the effects of fondaparinux, dabigatran, rivaroxaban or apixaban. Instead, chromogenic assays, one-step prothrombinase-induced clotting time test and the HepTest with reduced incubation time, are among the different or modified tests that appear to give the most reproducible and accurate results. The tests show variations in response to anticoagulants - some of which have clinical relevance. Thus, it is important to be aware of the observed variations in order to prevent the misinterpretation of test results.

Although there is no need for routine coagulation monitoring with rivaroxaban--an oral, direct factor Xa inhibitor--a haemostasis assay might be valuable to measure its pharmacodynamic effects. This study aimed to find assays, among those commercially available, to measure rivaroxaban pharmacodynamics. Several global conventional clotting tests, as well as clotting or chromogenic assays to measure anti-factor Xa activity, were studied. A thrombin generation test using calibrated automated thrombogram was also done. Tests were performed with the indirect factor Xa inhibitor fondaparinux for comparison. A concentration-dependent prolongation of prothrombin time (PT), dilute PT, and activated partial thromboplastin time was observed with rivaroxaban. The results varied depending on the reagents. This variability cannot be standardised with the international normalised ratio system commonly used for vitamin K antagonists. Using a standard calibration curve, PT test results can be expressed in plasma concentrations of rivaroxaban rather than PT seconds or ratio. Standard methods for HepTest and two-step prothrombinase-induced clotting time (PiCT) resulted in a paradoxical response, with low concentrations of rivaroxaban reducing clotting times. This was not observed with shorter incubation times, or when antithrombin-deficient (immunodepleted) plasma was used. The chromogenic tests found a dose-dependent relationship between anti-factor Xa activity and rivaroxaban concentration. Modified specific factor Xa chromogenic assays are being further investigated. One-step PiCT and HepTest with shortened incubation times, as well as the widely available PT assay (using a rivaroxaban calibrator) could be useful to monitor the pharmacodynamic effects of rivaroxaban accurately. Finally, all clotting and chromogenic assays showed a concentration-dependent effect induced by rivaroxaban.

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One hundred thirty patients with 170 epithelial ovarian tumors were prospectively studied with computed tomography (CT) before surgery. Ultrasound (US) was performed in 108 patients with 138 tumors. At pathologic examination, 78 tumors (46%) were benign, 14 (8%) borderline, and 78 (46%) malignant. CT results were compared with surgical and pathologic findings in all patients. CT enabled detection of 148 of 170 tumors (87%), and US enabled detection of 118 of 138 tumors (86%). Benign serous cystadenomas (n = 42) were correctly characterized with a sensitivity of 69% at CT and 70% at US. Benign mucinous cystadenomas (n = 21) were correctly characterized with a sensitivity of 62% at CT and 50% at US. Malignancy was suggested in nine of 14 patients (64%) with borderline tumors at CT and in five of 14 (36%) at US. The overall accuracy of characterization of benign versus malignant tumors (including borderline tumors) was 94% with CT and 80% with US. In the 108 patients studied with both CT and US, the sensitivity of CT was significantly superior to that of US (P less than .03), whereas there was no significant difference in specificity (P = .125).