Emmanuel J. Favaloro

Laboratory Testing in the Era of Direct or Non- Vitamin K Antagonist Oral Anticoagulants: A Practical Guide to Measuring Their Activity and Avoiding Diagnostic Errors

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.

International Survey on D-Dimer Test Reporting: A Call for Standardization

D-dimer is the biochemical gold standard for diagnosing a variety of thrombotic disorders, but result reporting is heterogeneous in clinical laboratories. A specific five-item questionnaire was developed to gain a clear picture of the current standardization of D-dimer test results. The questionnaire was opened online (December 24, 2014-February 10, 2015) on the platform Google Drive (Google Inc., Mountain View; CA), and widely disseminated worldwide by newsletters and alerts. A total of 409 responses were obtained during the period of data capture, the largest of which were from Italy (136; 33%), Australia (55; 22%), Croatia (29; 7%), Serbia (26; 6%), and the United States (21; 5%). Most respondents belonged to laboratories in general hospitals (208; 51%), followed by laboratories in university hospitals (104; 26%), and the private sector (94; 23%). The majority of respondents (i.e., 246; 60%) indicated the use of fibrinogen equivalent unit for expressing D-dimer results, with significant heterogeneities across countries and health care settings. The highest prevalence of laboratories indicated they were using ng/mL (139; 34%), followed by mg/L (136; 33%), and µg/L (73; 18%), with significant heterogeneity across countries but not among different health care settings. Expectedly, the vast majority of laboratories (379; 93%) declared to be using a fixed cutoff rather than an age-adjusted threshold, with no significant heterogeneity across countries and health care settings. The results of this survey attest that at least 28 different combinations of measurement units are currently used to report D-dimer results worldwide, and this evidence underscores the urgent need for more effective international joined efforts aimed to promote a worldwide standardization of D-dimer results reporting.

Allergy and Venous Thromboembolism: A Casual or Causative Association.

Allergic diseases are very frequent conditions worldwide. The pathogenesis of allergic reactions and venous thromboembolism (VTE) shares several risk factors and predisposing conditions. In particular, the concentration of immunoglobulin E (IgE) is considerably increased in patients with allergic diseases, and this immunoglobulin exert many prothrombotic and antifibrinolytic activities, especially through interaction with mast cells. Therefore, this narrative review is aimed to provide an overview of the current scientific evidence supporting a potential relationship between allergy and the risk of VTE. Although no prospective studies have been published so far, the evidence provided by six large cross-sectional studies and several case reports support the existence of an unquestionable epidemiological association between different allergic diseases (especially atopy, asthma, and celiac disease) and venous thrombosis. Two additional investigations reported that the concentration of IgE might predict the onset of severe complications of pulmonary embolism such as pulmonary infarction and pleural fluid accumulation. Therefore, the existence of a convincing epidemiologic link between allergy and VTE paves the way to future investigations aimed to establish whether the prevention or treatment of allergic diseases might be regarded as an effective measure to lower the risk of VTE.