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Imilar data are of particular importance since we cannot afford to deprive us ofEven if NOACs are presented as having a predictable pharmacodynamics and pharmacokinetics, several patients or situation could require an assessment of the degree of anticoagulation and probably a drug tailoring. The clinical situations include: recurrence of thrombosis or bleeding, before urgent surgery or procedure (with last administration in the last 24 h or more if CRCL <50mL/ min), before fibrinolytic therapy of acute ischemic stroke, in case of bridging therapy, in case of cardioversion and in the setting of dual or triple antithrombotic therapy, such as in the patient with AF undergoing a percutaneous coronary intervention, when dual platelet inhibitors may be added to NOACs, given that such patients represent a complex management PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/12958591 problem. In addition, several patterns in patient status could also require an assessment of the responsiveness at the individual level. This includes patients with risk factors for NOACs accumulation or too low levels (i.e. drug-drug interactions as with frequently used medication like amiodarone and verapamil), patients with extreme body weight (<50 kg or >110 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/18218841 3-Amino-1H-indazole-4-carbonitrile kg), patients with hepatic impairment, patients with renal impairment (in case of progressive decrease of renal function but also in acute decrease during dehydration, antibiotics administration, ...), in case Boc-D-Lys-OH of comorbidities or in elderly patients.How to accurately measure plasma drug concentrations?In this part of the manuscript, we review the different routine coagulation tests that could be used to estimate the intensity of anticoagulation in patients treated with dabigatran etexilate (the pro-drug of dabigatran, a direct thrombin inhibitor) and with rivaroxaban or apixaban, two direct factor Xa inhibitors. More specific assays used to accurately estimate plasma drug concentrations are also presented.Global coagulation tests Dabigatran: activated Partial Thromboplastin TimeThe recent recommendation of the Subcommittee of Control of Anticoagulation of the Scientific and Standardisation Committee of the ISTH, mentions that the aPTT using most available reagents can be used to determine the relative intensity of anticoagulation due to dabigatran. However, they state that aPTT should not be used to quantify the drug plasma concentration. They add that each laboratory should be aware of the sensitivity of their aPTT assays to dabigatran and this can be achieved using commercially available plasma calibrants [168]. However, it is unknown if specific dabigatran calibrants, used out ofDouxfils et al. Thrombosis Journal 2014, 12:24 http://www.thrombosisjournal.com/content/12/1/Page 11 oftheir dedicated platform context, are truthful calibrants that could reflect accurately the impact of dabigatran in plasma from patient's sample, since aPTT is affected by numerous pre-analytical and biological variables. It is stated in the EU-SmPC that when dabigatran was used for the prevention of stroke in NVAF with a bid dosing regimen, an aPTT ratio greater than 2xULN (or an aPTT prolongation of about 80 seconds) at trough (10-16 h after the previous dose) reflected the 90th percentile of observations (i.e. 200 ng/mL at Ctrough) and is considered to be associated with a higher risk of bleeding [169]. However, studies revealed that the inter-reagent variability prevents using an aPTT of about 80 seconds as reflecting plasma dabigatran concentration of 200 ng/mL [170] (Figure 1). Sim.