Background
Rivaroxaban is widely used in clinical practice. Although routine coagulation monitoring is not required, quantitative determination of rivaroxaban might be valuable in certain clinical circumstances. Variation in response sensitivity of prothrombin time (PT) reagents to rivaroxaban is well described in the literature, and the conventional international normalised ratio cannot be used for rivaroxaban.
Purpose
This multicentre study assessed the intra and interlaboratory precision of measurements of rivaroxaban plasma concentrations using the PT assay together with rivaroxaban calibrators and controls.
Materials and methods
Participating laboratories (Europe and North America) were provided with rivaroxaban calibrators (0, 41, 219 and 430 ng/ml), rivaroxaban pooled human plasma controls (19, 160 and 643 ng/ml) and PT reagent. Evaluation was performed over 10 consecutive days by each laboratory using local PT reagents as well as the centrally provided PT reagent (STA Neoplastine CI Plus; Diagnostica Stago). A calibration curve was produced each day, and day-to-day precision was evaluated by testing three control plasma samples. The control was diluted and re-tested if the level was above the highest concentration of the calibration curve.
Results
Intralaboratory variations in PT were dependent on the sensitivity of the local PT reagents, regardless of the type of instrument used. A large inter-laboratory variation (in seconds) was observed with local PT reagents; the coefficient of variation (CV) was 13.6–29.7%. When the results were expressed as rivaroxaban concentration (ng/ml), the inter-reagent variations were reduced; less variation was found with both local reagents (CV: 5.1–15.5%) and the central reagent (CV: 2.2–7.5%). However, over-estimation was observed with both local and central reagents. The CV for the calibrator containing 41 ng/ml rivaroxaban was 5.8% when the central reagent was used.
Conclusions
The PT assay may be useful for measuring rivaroxaban peak plasma concentrations (2–3 h after drug intake) using rivaroxaban calibrators and controls.
In seven patients with acquired von Willebrand's disease (AvWD) associated with lymphoproliferative disorders or benign monoclonal gammopathies, the platelet contents of von Willebrand factor antigen and ristocetin cofactor (vWF:Ag and vWF:RiCof, respectively) were normal. All the multimers of vWF:Ag could be seen in the 1.6% SDS- agarose gel electrophoresis patterns of plasma and platelet lysates. Infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) augmented plasma levels of vWF:Ag and vWF:RiCof of all patients and corrected prolonged bleeding times (BT). However, compared with patients with congenital vWD type I and comparable degrees of baseline abnormalities treated in the same way, vWF:Ag and vWF:RiCof were increased less and cleared more rapidly from plasma and the BT remained normal for a shorter period of time. These studies provide evidence that these AvWD patients have qualitatively normal vWF in plasma, but at lower concentrations, that vWF in platelets is normal both qualitatively and quantitatively, and that cellular vWF can be rapidly released into plasma by DDAVP to correct the hemostatic abnormalities. However, vWF is removed rapidly from plasma, making the correction more transient than in congenital vWD type I.
A multicentre, double-blind, randomised trial was conducted to compare the efficacy of a low-molecular-weight (LMW) heparin, Logiparin, with that of an unfractionated (UF) heparin in the prophylactic treatment of thrombosis in patients undergoing general surgery. A total of 1,290 patients were randomised to receive a single daily dose of Logiparin (2,500 IU: 431 patients; 3,500 IU: 430 patients) or UF heparin (2 × 5,000 IU: 429 patients). The incidence of the main end point, deep venous thrombosis, was found to be significantly different between the groups (p = 0.03), whereas the incidence of severe haemorrhage was not (p = 0.5). The plasma anti-Xa activity was found to be correlated with body weight, but correlated only very weakly with antithrombotic activity (p = 0.045) after adjustment in a stepwise multivariate analysis, and did not significantly correlate with the incidence of haemorrhage. Logiparin at 3,500 IU and UF heparin showed similar efficacy. Although a correlation between plasma anti-Xa activity and body weight was observed, there is not sufficient evidence to recommend the adjustment of the Logiparin dose on patient’s weight for prophylaxis in general surgery patients.
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