Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism

Bounameaux, Henri; Cirafici, P.; Moerloose, P de; Schneider, Pierre-Alain; Slosman, Daniel O.; Reber, Guido; Unger, Pierre-François

doi:10.1016/0140-6736(91)92158-x

Cited by 277 publications

(133 citation statements)

References 18 publications

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“…[1][2][3][7][8][9][10] However, because D-dimer levels may also be increased in a variety of nonthrombotic disorders, D-dimer is a sensitive but nonspecific marker for venous thrombosis. Consequently, although a positive result is not useful in confirming the diagnosis of DVT or PE, a negative result can aid in the exclusion of these conditions and limit the need for further investigation with expensive and invasive radiologic tests.…”

Section: • Myocardial Infarctionmentioning

confidence: 99%

“…Consequently, although a positive result is not useful in confirming the diagnosis of DVT or PE, a negative result can aid in the exclusion of these conditions and limit the need for further investigation with expensive and invasive radiologic tests. 1,3,[7][8][9][10] In hospitalized and other acutely ill patients commonly affected by the conditions listed in ►Table 1, D-dimer testing has less utility because of the high frequency of false-positive results. 7,11,12 Most of the data validating the use of D-dimer testing in suspected VTE come from evaluations of patients in the ambulatory setting (i.e., outpatient or emergency departments).…”

Section: • Myocardial Infarctionmentioning

confidence: 99%

“…To safely rule out VTE, a negative D-dimer assay result when used alone or with other tests, should yield equivalent failure rates in clinical follow-up as reference standard tests such as negative venography for DVT and negative pulmonary angiography or a normal ventilationperfusion lung scan for PE (i.e., failure rates of 2% or less; negative predictive value of at least 98%). 3,[7][8][9][10][11][12][13][15][16][17] Multiple studies have investigated the use of D-dimer testing, either alone or in combination with noninvasive tests or clinical pretest probability assessment, to manage patients with suspected lower extremity DVT or PE. 3,9,10,13,18-42 Based on the results of these investigations, recent guidelines recommend the use of initial D-dimer testing when evaluating patients with either a low (with either a moderately or highly sensitive D-dimer assay) or moderate pretest probability (highly sensitive D-dimer only) of DVT.…”

Section: • Myocardial Infarctionmentioning

confidence: 99%

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

Bates

2012

Semin Thromb Hemost

102

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: • Myocardial Infarctionmentioning

confidence: 99%

Section: • Myocardial Infarctionmentioning

confidence: 99%

Section: • Myocardial Infarctionmentioning

confidence: 99%

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

Bates

2012

Semin Thromb Hemost

102

103

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“…Although increased plasma DD level is generally thought to be associated with the presence of DVT, the positive predictive value of DD is 36 -44%. Conversely, the negative predictive value of DD is 89 -100% (Bounameaux et al, 1991;Harrison et al, 1993;Wells et al, 2003;Righini et al, 2006). We have recently reported that increased DD levels are associated with the presence of silent VTE before treatment in ovarian cancer (DD o1.5 mg ml À1 , 0 of 26 (0%); DD X1.5 mg ml À1 , 18 of 46 (39%)) .…”

mentioning

confidence: 99%

Silent venous thromboembolism before treatment in endometrial cancer and the risk factors

et al. 2008

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Venous thromboembolism (VTE) often occurs after surgery and can even occur before surgery in patients with gynaecological malignancies. We investigated the incidence of VTE before treatment of endometrial cancer and associated risk factors. Plasma D-dimer (DD) levels before initial treatment were examined in 171 consecutive patients with endometrial cancer. Venous ultrasound imaging (VUI) of the lower extremities was performed in patients with DD X1.5 mg ml À1 , as the negative predictive value of DD for VTE is extremely high. For patients with deep vein thrombosis (DVT), pulmonary scintigraphy was performed to ascertain the presence of pulmonary thromboembolism (PTE). Risk factors for VTE were analysed using univariate and multivariate analyses for 171 patients. Of these, 37 patients (21.6%) showed DD X1.5 mg ml À1 , 17 (9.9%) displayed DVT by VUI and 8 (4.7%) showed PTE on pulmonary scintigraphy. All patients with VTE were asymptomatic. Univariate analysis for various risk factors revealed older age, non-endometrioid histology and several variables of advanced disease as significantly associated with VTE before treatment. Obesity, smoking and diabetes mellitus were not risk factors. Multivariate analysis confirmed extrauterine spread and non-endometrioid histology as independently and significantly associated with risk of VTE. These data suggest that silent or subclinical VTE occurs before treatment in at least around 10% of patients with endometrial cancer. Risk factors for VTE before treatment might not be identical to those after starting treatment.

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“…The SF levels reflect the changes that occur during the early phase of a thrombotic event, while D-dimer levels reflect secondary fibrinolysis after clot formation (8). Elevated levels of circulating plasma SF indicate the conversion of fibrinogen to fibrin by thrombin.…”

Section: Discussionmentioning

confidence: 99%

Changes in soluble fibrin levels during the perioperative period of gynecologic cancer surgery

et al. 2012

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Abstract. The purpose of this study was to evaluate the changes in plasma soluble fibrin (SF) levels over time in gynecologic cancer patients following surgery. Furthermore, we examined the duration of the coagulation stage and determined a suitable duration for which thromboprophylaxis with anticoagulant agents should be administered. We retrospectively studied 311 patients with invasive gynecologic cancer who underwent surgery at Okayama University Hospital, Japan. The plasma SF levels were measured serially prior to the operation and on postoperative days 0, 1, 3, 5, 7, 10, 14, 21 and 28. The plasma SF levels increased rapidly, peaked on postoperative day 1 and then decreased. The SF levels of patients with venous thromboembolism (VTE) were significantly different from those of VTE-negative patients on postoperative days 0-10. The SF levels on each day did not significantly differ between patients treated with chemical anticoagulants and those treated mechanically. The plasma SF levels were elevated (≥7.0 µg/ml) in 159 of the 311 patients (51.1%) on one of the days when these levels were measured. Among the patients with elevated plasma SF levels, 110 patients (69.2%) peaked on days 0-3 and only 9 patients (5.7%) peaked on days 21-28. Although only 1 of the 14 patients (7.1%) who showed peak levels on day 14 had undergone chemotherapy following surgery, 8 of the 9 patients (88.9%) whose levels peaked on days 21-28 had undergone chemotherapy following surgery (P= 0.0002). In conclusion, the plasma SF levels increased rapidly, peaked on postoperative day 1 and then decreased. These levels peaked within 14 days of surgery in most cases. Therefore, chemical thromboprophylaxis may be administered for at least up to 14 days following surgery. IntroductionCancer is widely accepted as a risk factor for venous thromboembolism (VTE) and, to a lesser extent, arterial thrombosis. This risk is attributable to factors such as the expression of prothrombotic factors and compression of the blood vessels by tumors, inflammatory response to malignancies by the host, immobility, surgery, indwelling central venous catheters, and certain antitumor therapies (1). In surgical oncology patients, VTE is the predominant cause of mortality during the first 30 postoperative days (2). VTE is also a common complication associated with gynecologic cancer surgery, and patients with gynecological malignancies are classified under the highestrisk group (3).Coagulation and fibrinolysis in the blood are complex processes, and numerous markers of thrombin and plasmin action in patients with VTE have been identified (4). Soluble fibrin (SF) and D-dimer are sensitive markers for VTE. D-dimer is a stable end-product of fibrin degradation, and D-dimer levels increase as a result of fibrin formation and fibrinolysis. Conversely, SF reflects thrombi activation and the cleavage of fibrinogen during the early stage of disease and is used as an indicator of coagulation (5). We recently reported the changes in plasma D-dimer levels over time in gynecologi...

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Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism

Cited by 277 publications

References 18 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

Silent venous thromboembolism before treatment in endometrial cancer and the risk factors

Changes in soluble fibrin levels during the perioperative period of gynecologic cancer surgery

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