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  • br Conclusions and perspectives In conclusion offering

    2021-11-19


    Conclusions and perspectives In conclusion, offering duly validated and highly performing assays for measuring DiXaIs in plasma is a step, but not the final issue. More dedicated and individual assays will continue this innovative development, which witnesses the need for collaboration between complementary organizations, including pharmaceutical industry, regulatory bodies, diagnostic industry and clinical/university investigators for continuously improving anticoagulated patients' efficacy and safety. The avenue open by Michel Meyer Samama, and others, is still a challenge for all professionals dealing with prevention and treatment of thrombosis, and all laboratory environment, and we are proud to follow his teaching in that way [55].
    Acknowledgements
    During the last 2 decades, advancement in the treatment and supportive care of critically ill children and the increasing use of central venous catheters has contributed to an increase in the annual rate of venous and arterial thromboembolic events among hospitalized neonates and children., Nonetheless, there is a lack of high-quality evidence to guide anticoagulation management in this cohort, and treatment is commonly extrapolated from adult practice. Although low-molecular-weight heparin and direct oral anticoagulants increasingly are being used to treat and prevent thromboembolism in children, unfractionated heparin remains an important anticoagulant in the inpatient setting, particularly in critically ill patients. Unfractionated heparin exerts its anticoagulant activity primarily via antithrombin-mediated inhibition of thrombin and factors Xa, IXa, and XIa. Given its short Dasatinib Monohydrate and immediate, complete reversibility with protamine sulfate, unfractionated heparin allows close titration of anticoagulation in children perceived to be at high risk of bleeding and those on extracorporeal membrane oxygenation (ECMO) and left ventricular assist devices (LVADs). Unfractionated heparin drug monitoring is aimed at balancing the anticoagulant effect and the risk of treatment-related bleeding complications. The activated partial thromboplastin time (APTT) is a global test of coagulation that measures the integrity of the intrinsic and common coagulation pathways. Initially described as a screening tool for hemophilia, the APTT has been used widely to monitor unfractionated heparin. Basu et al demonstrated that the risk of recurrent thrombosis in adults receiving unfractionated heparin could be significantly reduced by aiming for a 1.5-2.5 times prolongation of the APTT. Subsequently, it was realized that the measurement of APTT is affected by several preanalytical, analytical, and biological variables, particularly in children. APTT testing is sensitive to inappropriate sample collection, handling, and processing, leading to erroneous results. The measurement of APTT is sensitive to the reagent and coagulometer used for testing, and the implications of the resultant variability in the level of anticoagulation achieved with a fixed APTT goal are significant., The lack of standardization of reagents used in APTT testing adds to the interlaboratory variability. In addition, baseline APTT is relatively prolonged in neonates and young infants; hence, absolute APTT therapeutic ranges calculated using adult plasma likely represent subtherapeutic anticoagulation., , The anti-factor Xa heparin assay (Anti-FXa) is an automated, chromogenic or clotting-based assay that measures the factor Xa neutralizing capacity of heparin and is a more direct measure of the heparin level in the plasma. The measurement of Anti-FXa is also influenced by preanalytical and analytical variables, but it fluctuates less than APTT. More importantly, biological variables like liver disease, increased level of acute-phase reactants, and presence of lupus anticoagulant that affect APTT measurement do not interfere with Anti-FXa testing., The American College of Chest Physicians and the College of American Pathologists recommend that the APTT range used to monitor unfractionated heparin should correspond to a heparin level of 0.3-0.7 units/mL measured by an Anti-FXa assay or 0.2-0.4 units/mL measured by protamine titration., With the increased availability of automated Anti-FXa assays in clinical practice, several investigators sought to explore the correlation between the time-trusted APTT and newer Anti-FXa assays., , , Pediatric studies have had varying limitations, including retrospective study design, small sample size, and/or heterogeneous patient populations, specifically inclusion of neonates and patients on ECMO and LVADs., , , , ,