Ity of the PT for rivaroxaban-spiked plasmas (see text more details). The Riva-SI relatively to the common standard is reported on each graph. By definition the higher the Riva-SI the lower the responsiveness of the thromboplastin to the effect induced by rivaroxaban. The numbers in brackets represent the coefficient of variation of the slope estimation. The Riva-SI for the common standard has been arbitrarily set at 1.00. Results did not change appreciably when Neoplastin Plus was used as the common standard [9].Tripodi Thrombosis Journal 2013, 11:9 http://www.thrombosisjournal.com/content/11/1/Page 3 ofin detail [9], adopted the same statistical procedure recommended by WHO for the determination of the ISI of thromboplastins used for patients on VKA [4]. The numerical PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/744568 value of the slope, provisionally called rivaroxaban sensitivity index (Riva-SI), can then be used to convert results of the PT (seconds) into a new scale, called rivaroxaban standardized ratio (Riva-PT-ratio), according to the equation: ? iva-SI Riva-PT-ratio ?PTpatient =PTnormalThis system of standardization proved feasible [9] for the following reasons. (i) Six thromboplastins testing plasmas spiked with rivaroxaban yielded results that were linearly related to those of a common thromboplastin standard; (ii) the data points could be represented by a best-fit orthogonal regression line and (iii) the slope of the line could be estimated with a high degree of confidence with CV value (that is a measure of the calibration precision) less than the required 3 [4] (see Figure 1). The responsiveness to rivaroxaban was the highest for Neoplastin Plus (Stago, Asnieres, France) and Recombiplastin (Instrumentation Laboratory, Orangeburg, NY) (i.e., Riva-SI close to unity) and the lowest for Innovin (Siemens Health Care Diagnostics, Marburg, Germany) (Riva-SI = 1.712) (see Figure 1). Interestingly, the responsiveness to rivaroxaban does not depend on the species of the thromboplastin as shown by the evidence that two human recombinant thromboplastins such as Recombiplastin and Innovin display similar responsiveness to VKA, but completely different responsiveness to rivaroxaban (see Figure 1). In the second step of the study, the above system of standardization was validated by testing three rivaroxabanspiked plasmas (that Fmoc-Oic-OH were different from those used for the determination of the Riva-SI) [9]. The overall between-thromboplastin variability of the PT results (S)-1-Boc-2-Hydroxymethyl-piperazine that was on average 14.1 or 29.6 when results were expressed as PT-ratio or INR was reduced to a mere 2.1 when results were expressed as Riva-PT-ratio [9]. These results and conclusions were recently confirmed by Harenberg et al. [10]. The Riva-PT-ratio although feasible should be further investigated to address practical issues that have been previously discussed in detail [9]. For instance, in the model so far proposed normal plasmas spiked with increased amounts of rivaroxaban have been used PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/10811056 to determine the Riva-SI for the working thromboplastins. These plasmas although representative do not necessarily mirror the real situation of plasmas from patients treated with rivaroxaban. This issue had already been considered for the calibration of the INR in patients on VKA and guidelines have been issued on preparation,certification and use of certified plasmas for ISI calibration and INR determination [11]. Further work is, therefore, needed to give specific details on the preparation, certification, validation and use of ri.