Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy

Rodger, Marc; Kahn, Susan R.; Wells, Philip S.; Anderson, David R.; Chagnon, Isabelle; Gal, Grégoire Le; Solymoss, Susan; Crowther, Mark; Perrier, Arnaud; White, Richard; Vickars, Linda M.; Ramsay, Tim; Betancourt, Marisol; Kovacs, Michael J.

doi:10.1503/cmaj.080493

Cited by 516 publications

(353 citation statements)

References 37 publications

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“…Rodger et al prospectively followed 600 patients with a first unprovoked venous thromboembolic event for a mean of 18 months following cessation of anticoagulant therapy. 80 The investigators used 69 potential predictors of recurrence documented before warfarin cessation to determine a rule that could identify patients with an annual risk of VTE of less than 3%. No combination of clinical predictors satisfied this criteria in men; however, women with one or fewer of leg hyperpigmentation, edema, redness; VIDAS D-dimer level of 250 μg FEU/L or greater while taking warfarin; body mass index of at least 30 kg/m 2 or age 65 years or greater had an annual risk of recurrence of 1.6% (95% CI, 0.3 to 4.6%).…”

Section: D-dimer Testing For Duration Of Anticoagulant Therapymentioning

confidence: 99%

D-Dimer Assays in Diagnosis and Management of Thrombotic and Bleeding Disorders

Bates

2012

Semin Thromb Hemost

103

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).D-dimer is a global indicator of coagulation activation and fibrinolysis and, therefore, an indirect marker of thrombotic activity. This specific cross-linked fibrin degradation product is formed through the sequential action thrombin, activated factor XIII (FXIIIa), and plasmin (►Fig. 1). 1-3 First, thrombin, generated when coagulation is activated, converts fibrinogen to fibrin and activates FXIII. Second, FXIIIa covalently crosslinks D-domains in adjacent fibrin monomers. Third, plasmin (formed on the fibrin surface by plasminogen activation) cleaves substrate fibrin at specific sites, and when it cleaves fibrin cross-linked by FXIIIa, it generates D-dimer. D-dimer is cleared through the kidneys and the reticuloendothelial system and has a plasma half-life of approximately 8 hours. 4 Low levels of D-dimer can be found circulating under normal physiologic conditions, while pathologically elevated levels can be found in any condition associated with enhanced fibrin formation and fibrinolysis (►Table 1). 1-3 The utility of D-dimer measurement has been evaluated in several clinical situations; however, the D-dimer assays have been best validated for the exclusion of venous thromboembolism (VTE) and the diagnosis and monitoring of disseminated intravascular coagulation (DIC). This article will review the available evidence for the utilization of D-dimer antigen measurement in the management of thrombotic and bleeding disorders. Measurement of D-DimerThe presence of D-dimer in plasma can be detected using monoclonal antibodies that recognize an epitope present in FXIIIa-cross-linked fragment D-domain of fibrin but not in fibrinogen degradation products or noncross-linked fibrin degradation products. Many different D-dimer assays have been developed and marketed. All of these tests rely on the use of monoclonal antibodies to detect D-dimer molecules. In general, three techniques are available to assay D-dimer (►Fig. 2). 1-3 These are (1) enzyme-linked immunosorbent assays (ELISAs) that rely on antibody capture and labeling of D-dimer; (2) a whole-blood agglutination assay (SimpliRED, Siemens Healthcare Diagnostics, Newcastle, DE), that uses a bispecific antibody conjugate with binding sites for both D-dimer and a red cell antigen and is performed on whole blood; (3) latex agglutination assays that also use bispecific antibodies with specificity for the latex particle and D-dimer antigen. Earlier latex agglutination assays for D-dimer were qualitative or semiquantitative; however, newer automated, quantitative D-dimer assays (which are immunoturbidometric assays) are performed on routine, automated coagulation instruments. It is important to recognize that results are not comparable between different assays, even between those of similar formats. Potential reasons for the lack of comparable results are listed in ►Table 2. Numeric results of D-dimerAbstract D-dimer is a global indicator of coagulation activation and fibrinolysis and, therefore, an indirect marker of thrombotic activity. The utility of D-dimer measur...

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Section: D-dimer Testing For Duration Of Anticoagulant Therapymentioning

confidence: 99%

D-Dimer Assays in Diagnosis and Management of Thrombotic and Bleeding Disorders

Bates

2012

Semin Thromb Hemost

103

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“…This approach also seems more patient‐friendly as only one (outpatient) contact moment, which can be combined with blood draw, is necessary. This was for example done in the derivation and in the majority of patients in the validation study of the HERDOO2 model, in which d ‐dimer levels were measured on vitamin K antagonist (VKA) treatment 8, 9. Treatment with VKA influences d ‐dimer levels, probably due to its anticoagulant effect 10.…”

Section: Introductionmentioning

confidence: 99%

Measurement of coagulation factors during rivaroxaban and apixaban treatment: Results from two crossover trials

Scheres

Lijfering

Cheung

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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BackgroundPrediction models for venous thromboembolism recurrence will likely be improved by adding levels of coagulation factors. Risk assessment is ideally performed during anticoagulant treatment, however, the influence of direct oral anticoagulants on coagulation factors is uncertain.ObjectiveTo assess the influence of rivaroxaban and apixaban on several coagulation factor levels.MethodsIn two crossover trials we assessed the influence of rivaroxaban and apixaban intake on factor (F)VIII, FXI and FXII‐activity and fibrinogen, von Willebrand factor (VWF:Ag), and d‐dimer levels. At three sessions with a washout period in between, blood was taken from 12 healthy male individuals immediately before intake of rivaroxaban 15 mg twice daily (n = 6) or apixaban 10 mg twice daily (n = 6) and three hours after the last intake.ResultsOverall, measured levels were lower after rivaroxaban/apixaban intake. The paired mean difference after rivaroxaban intake was −38 IU/dL (95% CI −43; −33) for FVIII:C, −29 U/dL (95% CI −45; −12) for FXI:C, −22 IU/dL (95% CI −43; −1) for FXII:C, −0.11 g/L (95% CI −0.25; 0.03) for fibrinogen, −7 IU/dL (95% CI −18; 3) for VWF:Ag, −27 ng/mL (95% CI −50; −4) for d‐dimer and −0.36 (95% CI −0.57; −0.15) for Ln d‐dimer. After apixaban intake this was −29 IU/dL (95% CI −38; −21) for FVIII:C, −29 IU/dL (95% CI −36; −22) for FXI:C, −19 IU/dL (95% CI −24; −15) for FXII:C, −0.18 g/L (95% CI −0.33; 0.03) for fibrinogen, −52 ng/mL (95% CI −100; −4) for d‐dimer, 0.25 (−0.60; 0.09) for Ln d‐dimer and 1 IU/dL (95% CI −7; 9) for VWF:Ag.Conclusion FVIII:C, FXI:C, FXII:C, and d‐dimer measurements were influenced by rivaroxaban/apixaban intake, while fibrinogen and VWF:Ag were not.

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“…All four HAS‐BLED users (Brazil, Canada, Poland, the Netherlands) indicated cognizance of the score's original purpose, yet hailed its usefulness and applicability to bleeding risk assessment in VTE, especially in the absence of a dedicated VTE bleeding risk score. Other risk scores that were mentioned by the interviewees were the “Men continue and HER DOO2” clinical decision rule proposed in the REVERSE15 cohort study (Canada), the Padua risk score for VTE (Philippines)16 and the Caprini score for DVT (Philippines) 17…”

Section: Resultsmentioning

confidence: 99%

Secondary prophylaxis decision‐making in venous thromboembolism: interviews on clinical practice in thirteen countries

Cate

Prins

2017

Research and Practice in Thrombosis and Haemostasis

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Essentials Thrombosis experts still struggle to reach consensus regarding the optimal type, dosage and duration of treatment.We asked 13 leaders in the field to comment on the prevention of venous thromboembolism (VTE) in their respective countries.Universally relevant risk factors as well as area‐specific barriers to adequate treatment are identified.Local guidelines may be beneficial to guide decision‐making in areas where universal guidelines fall short. ObjectivesSecondary prevention of venous thromboembolism (VTE) remains a topical and contentious point of debate for thrombosis experts around the globe. This discussion centers around two aspects: optimum treatment duration and which type and dosage of thromboprophylaxis to prescribe. Collectives of thrombosis experts have tried to steer the debate by issuing periodical best‐practice guidelines. However, the lack of adherence to said guidelines is such that there is a growing body of research devoted to this very problem. Most of the studies on the subject retrospectively observe a single setting, which leaves important questions as to the generalizability of their findings. As each setting appears to face its own unique challenges, the overarching question of why there is so much variance between physicians when it comes to the secondary prevention of VTE is never fully addressed.MethodsFor this study, we asked thirteen senior‐level physicians representing equally as many countries about the current state of clinical practice regarding the secondary prevention of VTE.ResultsThe discussion identifies several barriers to adequate VTE prevention, and hints at area‐specific idiosyncrasies that may explain why physicians from different locales treat VTE patients differently.ConclusionUniversal treatment guidelines may not fully translate to clinical practice in many areas, and that promoting local guidelines to supplement the universal guidelines may be beneficial.

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Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy

Cited by 516 publications

References 37 publications

D-Dimer Assays in Diagnosis and Management of Thrombotic and Bleeding Disorders

D-Dimer Assays in Diagnosis and Management of Thrombotic and Bleeding Disorders

Measurement of coagulation factors during rivaroxaban and apixaban treatment: Results from two crossover trials

Secondary prophylaxis decision‐making in venous thromboembolism: interviews on clinical practice in thirteen countries

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