Systematic Review: <scp>d</scp>-Dimer to Predict Recurrent Disease after Stopping Anticoagulant Therapy for Unprovoked Venous Thromboembolism

Verhovsek, Madeleine; Douketis, James D.; Yi, Qilong; Shrivastava, Sadhana; Tait, Robert C.; Baglin, Trevor; Poli, Daniela; Lim, Wendy

doi:10.7326/0003-4819-149-7-200810070-00008

Cited by 249 publications

(151 citation statements)

References 44 publications

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“…D-Dimer is a well-studied biomarker in the diagnosis and management of VTE and a risk factor for VTE recurrence with potential implications for deciding on the duration of oral anticoagulation for secondary VTE prophylxis in noncancer patients. [26][27][28][29] sPselectin is a cell adhesion molecule that promotes thrombus formation and exhibits procoagulant properties per se. 26,30,31 Recent data suggest that sP-selectin is associated with primary and recurrent thrombosis in noncancer patients.…”

Section: Discussionmentioning

confidence: 99%

Prediction of venous thromboembolism in cancer patients

Ay¹,

Dunkler²,

Marosi³

et al. 2010

Blood

686

600

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The risk of venous thromboembolism (VTE) is increased in cancer patients. To improve prediction of VTE in cancer patients, we performed a prospective and observational cohort study of patients with newly diagnosed cancer or progression of disease after remission. A previously developed risk scoring model for prediction of VTE that included clinical (tumor entity and body mass index) and laboratory (hemoglobin level and thrombocyte and leukocyte count) parameters was expanded by incorporating 2 biomarkers, soluble P-selectin, and D-Dimer. Of 819 patients 61 (7.4%) experienced VTE during a median follow-up of 656 days. The cumulative VTE probability in the original risk model after 6 months was 17.7% in patients with the highest risk score (> 3, n ‫؍‬ 93), 9.6% in those with score 2 (n ‫؍‬ 221), 3.8% in those with score 1 (n ‫؍‬ 229), and 1.5% in those with score 0 (n ‫؍‬ 276). In the expanded risk model, the cumulative VTE probability after 6 months in patients with the highest

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Section: Discussionmentioning

confidence: 99%

Prediction of venous thromboembolism in cancer patients

Ay¹,

Dunkler²,

Marosi³

et al. 2010

Blood

686

600

View full text Add to dashboard Cite

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“…Two systematic reviews that examined the use of D-dimer measured after discontinuation of anticoagulants for unprovoked VTE reported approximately a doubling of the risk of recurrence for those with a positive D-dimer result compared with those with a negative D-dimer. 71,72 In only one of the studies included in these meta-analyses was D-dimer measurement used to manage patients. The PROLONG study was a multicentre trial of 708 patients with a first unprovoked venous thromboembolic event who had received at least 3 months of oral anticoagulant therapy.…”

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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“…[22][23][24][25][26][27][28] A meta-analysis, including seven studies of 1,888 patients who completed at least 3 months of anticoagulation, found that a D-dimer level of less than approximately 500 ng/mL ("a negative test") was associated with a 3.5% (95% CI, 2.7-4.3) annual risk of recurrence, whereas a D-dimer over this level ("a positive test") was (Table 2). 29 Potential difficulties of this approach, however, are lack of agreement and different cutpoints for the various D-dimer assays (there is no D-dimer "standard"). Clinicians must, therefore, rely on an assay manufacturer's cutpoint for a positive or negative D-dimer test based on individual studies using D-dimer to assess recurrence risk.…”

Section: Clinical Vignette: a 52-year-old Male Presented With An Unprmentioning

confidence: 99%

Duration of Anticoagulation: Applying the Guidelines and Beyond

Bauer

2010

Hematology

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Despite an improved understanding of the risk factors underlying venous thromboembolism (VTE), extensive clinical investigation, and detailed clinical guidelines, the decision to extend anticoagulation indefinitely for an individual patient with VTE is often problematic. Patients with VTE in association with major surgery, trauma, immobilization, or pregnancy are at relatively low risk of recurrence and generally do not require more than 3 to 6 months of anticoagulant therapy. For patients with a first unprovoked, or idiopathic, episode of VTE, an individualized approach should be taken in deciding on the duration of anticoagulation based on the patient's recurrence and bleeding risk, as well as their personal preference. Although the presence of genetic thrombophilic disorders (factor V Leiden and prothrombin G20210A gene mutations; deficiencies of antithrombin, protein C, and protein S) predispose patients to a first episode of VTE, there is inconsistent data on whether testing for these defects changes patient outcomes or should alter their management. In patients with a single unprovoked VTE, measurement of D-dimer several weeks following the completion of anticoagulant therapy appears useful in stratifying patients with a first unprovoked episode of VTE with regard to recurrence risk. Through a series of clinical vignettes, the utility of the laboratory in risk-stratifying patients with respect to recurrence risk will be discussed, along with decision making regarding the duration of anticoagulation. The potential impact of having a nonremovable inferior vena caval filter will also be addressed.

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Systematic Review: d-Dimer to Predict Recurrent Disease after Stopping Anticoagulant Therapy for Unprovoked Venous Thromboembolism

Cited by 249 publications

References 44 publications

Prediction of venous thromboembolism in cancer patients

Prediction of venous thromboembolism in cancer patients

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

Duration of Anticoagulation: Applying the Guidelines and Beyond

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