Determinazione dei farmaci anticoagulanti orali diretti in regime di urgenza. Determination of direct oral anticoagulant drugs in emergency. Guidelines for laboratory and istological diagnosis of celiac disease. Revision 2015.

Background: For over a year, even in Italy, are in use the new oral anticoagulants direct: dabigatran, a direct thrombin antagonist, and rivaroxaban, direct inhibitor of factor Xa. The advantage of these new drugs, with the same efficacy and safety compared to anticoagulants vitamin K antagonists, is due to their fixed-dose administration, the fewer drug interactions and no with the food, but most do not require monitoring of laboratory, if we exclude the periodic assessment of renal function. They have a short half-life, beginning and end of action fast. On the other hand, potential drawbacks regarding the use of these drugs are represented by the lack of antidotes in case of overdose or bleeding and the difficulty of controlling patient adherence. From a laboratory point of view the disadvantage is given by the difficulty of monitoring their effect with the current test, because the standard tests are not sufficient to provide an accurate answer, because of their poor or excessive sensitivity. Each Laboratory must therefore be organized in order to determine, in the presence of major bleeding events and/or to perform emergency surgery, the level of anticoagulation patient’s blood. The best way to answer the clinical question will therefore give the value of the drug present in that moment in the patient plasma. The purpose of this work is the development of the dosage of these drugs in the coagulometer available in our laboratory, in order to provide in the future, even in the regime of urgency, a quick response to the clinician. Methods: The methods for the assay of new oral anticoagulants direct were applied on the instrument BCS XP (Siemens Healthcare, Erlangen, Deutschland). The kit used for the quantitative determination of dabigatran is the BC Thrombin (Siemens Healthcare), the reagent used to assess the thrombin time in citrated human plasma. The method was suitably modified to provide a thrombin time defined diluted. The kit used for the quantitative determination of rivaroxaban is Berichrom Heparin (Siemens Healthcare) chromogenic assay specific for factor Xa. It was possible to build the appropriate calibration curves thanks to plasma calibrators and verificate with control plasma supplied by Hyphen BioMed (Neuville-sur-Oise, France). Results: The methods used are reliable and reproducible in a range between 24 and 497 ng/ml. Below 24 ng/ml will not be possible to give an exact value and values greater than 497 ng/ml, if required, will be necessary to dilute the sample. The coefficients of variation percentage intra-day and inter-day are all below 10% and the calibration curves have an r2=0.96$r^{2} = 0.96$. Conclusions: Our study shows that the methods selected and applied on coagulometer BCS XP in use in our laboratory are performed with the automatic procedure, in regime of urgency, in a time of about 30 minutes. The increase in the use of these drugs in clinical practice will help doctors to assess how the amount of the drug in plasma can be linked with the ability of the patient anticoagulant. © 2015, Springer-Verlag Italia.