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Favaloro E.J.,Institute of Clinical Pathology and Medical Research ICPMR | Franchini M.,Carlo Poma Hospital | Lippi G.,Laboratory of Clinical Chemistry and Hematology
Seminars in Thrombosis and Hemostasis | Year: 2014

The incidence of venous thromboembolism (VTE) is well recognized to increase with aging. Concurrently, the plasma concentrations of many coagulation factors (e.g., fibrinogen, factor [F] V, FVII, FVIII, and FIX) increase with aging, as does von Willebrand factor (VWF), thrombin generation, and platelet activation. Data are conflicting regarding age-related changes in the natural anticoagulants, including protein C, protein S, and antithrombin. Changes are also observed with components of the fibrinolytic pathway. All in all, aging is associated with a variety of hemostasis changes that on balance reflects a heightened procoagulant status compared with earlier age. It has to be recognized that as this occurs in the otherwise normal general population, this can also be considered a normal phenomenon of progressive life. An element of this heightened procoagulant status may reflect ongoing inflammatory processes, given some markers, notably FVIII and fibrinogen, are acute phase reactants. A variety of acquired prothrombotic risk factors (e.g., cancer, autoimmune disorders, and diabetes) also gradually develop with aging, some of which may induce profound abnormalities of hemostasis, and confound the age-related changes in hemostasis, as well as their influence on thrombotic risk. In this article, we review the changes in hemostasis markers measurable within many hemostasis laboratories, and consider many of the important implications for clinical and laboratory practice. Apart from representing an increased thrombotic risk, additional considerations entail the potential need (1) to utilize age-adjusted normal ranges (e.g., for D-dimer), (2) to consider the consequence on previous diagnoses (e.g., mild type 1 von Willebrand disease [VWD], where VWF test results may normalize with aging), and (3) to consider the effect of these changes of risk factors on the (perceived) therapeutic efficacy of antithrombotic medications such as aspirin. © Georg Thieme Verlag KG Stuttgart. New York. Source

Favaloro E.J.,Institute of Clinical Pathology and Medical Research ICPMR | Lippi G.,Laboratory of Clinical Chemistry and Hematology
Seminars in Thrombosis and Hemostasis | Year: 2015

A new generation of antithrombotic agents has recently emerged. These provide direct inhibition of either thrombin (factor IIa [FIIa]) or FXa, and are increasingly replacing the classical anticoagulants (heparin and coumarins such as warfarin) in clinical practice for a variety of conditions. These agents have been designated several acronyms, including NOACs, DOACs, and TSOACs, respectively, referring to new (novel; non-vitamin K antagonist) oral anticoagulants, direct oral anticoagulants, and target-specific oral anticoagulants, and currently include dabigatran (FIIa inhibitor), and rivaroxaban, apixaban, edoxaban, and betrixaban (FXa inhibitors). The pervading mantra that NOACs do not require laboratory monitoring is countered by ongoing recognition that laboratory testing for drug effects is needed in many situations. Moreover, since these agents do not require laboratory monitoring, some clinicians inappropriately take this to mean that they do not affect hemostasis tests. This review aims to briefly review the laboratory studies that have evaluated the NOACs against a wide range of laboratory assays to assess utility for qualitative or quantitative measurements of these drugs, as well as interferences that may cause misdiagnosis of hemostatic defects. Point of care testing, including use of alternate samples such as urine and serum, is also under development but is not covered extensively in this review. The main aims of this article are to provide practical guidance to general laboratory testing for NOACs, as well as to help avoid diagnostic errors associated with hemostasis testing performed on samples from treated patients, as these currently comprise major challenges to hemostasis laboratories in the era of the NOACs. © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York. Source

Lippi G.,Laboratory of Clinical Chemistry and Hematology
Scandinavian Journal of Clinical and Laboratory Investigation | Year: 2014

The laboratory assessment of cardiospecific troponins(s) represents the cornerstone for the diagnosis of acute coronary syndrome (ACS). Although troponin immunoassays are classified according to either analytical imprecision or percentage of measurable values in a presumably healthy population, it is rather clear that the nomenclature of commercial methods according to these systems of classification carries several drawbacks. The leading problems in classification according to imprecision are represented by the arbitrarity of optimal imprecision threshold, the uncertain correspondence between analytical performance and clinical outcomes and the improper use of terms, which has also been magnified by the lack of specific focus on this topic by regulating bodies such as the US Food and Drug Administration (FDA) and the European Union. Additional issues emerging from classification according to percentage of measurable values include the characterization of healthy population, the variation of values according to age, gender and race, as well as the influence of comorbidities. Considering that what really matters from a clinical standpoint is the clinical performance of the assay rather than the claimed analytical characteristics, it seems reasonable at this point in time to introduce a paradigm shift and gradually abandon the former analytical classification in favour of a different approach, preferable based on clinical outcomes. © 2014 Informa Healthcare. Source

Lippi G.,Laboratory of Clinical Chemistry and Hematology
European Journal of Internal Medicine | Year: 2013

A timely and efficient diagnosis is critical in patients with chest pain, to optimize the efficacy of myocardial revascularization in those with an acute coronary syndrome, and offset the increasing overcrowding in the emergency room by early discharge of subjects without myocardial ischemia. Although cardiospecific troponins remain the biochemical gold standards for diagnosing an acute coronary syndrome, several additional biomarkers have been proposed. As a general rule, there are important issues that should be addressed when combining an innovative diagnostic test with troponin, including a benchmark evaluation of diagnostic performance, the impact on throughput and turnaround time, along with the analytical features of the assay and the cost to benefit ratio of a multi-marker approach. Despite a considerable amount of data has been published, there is insufficient analytical and clinical evidence to support the use of most of these novel biomarkers as surrogates or in combination with troponin for diagnosing ischemic heart disease, especially when the latter is assessed with the novel highly-sensitive immunoassays. © 2012 European Federation of Internal Medicine. Source

Lippi G.,Laboratory of Clinical Chemistry and Hematology | Favaloro E.J.,Institute of Clinical Pathology and Medical Research ICPMR | Mattiuzzi C.,Service of Service of Clinical Governance
Seminars in Thrombosis and Hemostasis | Year: 2015

The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo © 2015 by Thieme Medical Publishers, Inc. Source

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