Identification of D dimer-E complex in disseminated intravascular coagulation

Whitaker, A N; Rowe, E.; Masci, Paul P.; Gaffney, Patrick J.

doi:10.1016/0049-3848(80)90340-0

Cited by 34 publications

(10 citation statements)

References 13 publications

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“…18 In contrast, proteolysis of fibrinogen or non-crosslinked fibrin (non-XL-Fg) results in formation of monomeric fragment D. The dimeric D-domain therefore may serve as indicator of in vivo fibrin formation. 19 Monoclonal antibodies generated by immunisation with fragment DD react with XL-Fg in general, including fibrin oligomers of variable size. 20 21 DD testing has limited specificity because many conditions are associated with fibrin formation (box 1).…”

Section: See End Of Article For Authors' Affiliationsmentioning

confidence: 99%

Role of fibrin D-dimer testing in emergency medicine

Wakai

2003

Emergency Medicine Journal

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Objectives: Systemic values of the fibrinolytic plasma marker fibrin D-dimer are raised in a variety of acute clinical conditions. D-dimer values can now be rapidly determined and used to aid diagnosis in emergency medicine. However, despite clinical guidelines, inappropriate and unnecessary measurement of D-dimer 1 Systemic DD values are raised in a variety of clinical conditions 2-7 and inclusion of DD testing may provide cost effective diagnostic strategies.8 9 In addition to the diagnostic use of DD, it may also be of potential prognostic use in many conditions. 10-14 Currently, despite the implementation of clinical guidelines, inappropriate DD testing is a significant problem. 15 It is, consequently, valuable for emergency physicians to be knowledgeable about the pathophysiological basis and limitations of DD testing to ensure its appropriate clinical use.The place of DD measurement in the diagnostic investigation of suspected venous thromboembolism (VTE) is now well established. This review updates experience on DD testing for VTE and discusses potential areas for the extension of indications for DD testing in emergency medicine. PATHOPHYSIOLOGY OF FIBRIN DDPlasmin is the fibrinolytic enzyme derived from its inactive precursor, plasminogen, by the action of thrombin and plasminogen activators. The main plasminogen activators are tissue plasminogen activator (tPA) and pro-urokinase, which is activated into urokinase by, among others, the contact system of coagulation. 16 Plasmin is neutralised by α 2 antiplasmin thereby restricting its fibrinogenolytic activity and localising the fibrinolysis on the fibrin clot. 16Fibrin is the main component of a thrombus. It is formed by the activation of the coagulation system. Its production is followed by activation of the fibrinolytic system, resulting in plasmin generation and subsequent fibrin lysis (fig 1). Under normal physiological conditions there is a balance of the two opposing processes. Dissolution of crosslinked fibrin (XL-Fg) leads to formation of specific degradation products, including DD, 17 which can be measured in both whole blood and plasma using monoclonal antibodies directed against epitopes located in the DD fragment. The activity of DD is considered to reflect the overall activity of clot formation and lysis. Because DD is not artificially generated in vitro during blood collection, its measurement more consistently reflects in vivo haemostatic activity than do other assays for coagulation or fibrinolytic activities that may be activated in vitro. Its absence excludes the presence of intravascular thrombus. Abbreviations: DD, D-dimer; VTE, venous thromboembolism; tPA, tissue plasminogen activator; XL-Fg, crosslinked fibrin; FDP, fibrin degradation product; ELISA, enzyme linked immunosorbent assay; HMW, high molecular weight; LMW, low molecular weight; FACT, Fibrin Assay Comparison Trial; CT, computed tomography; PE, pulmonary embolism; DVT, deep vein thrombosis; PTP, pretest probability; CHD, coronary heart disease; ACS, acute coronary syndrom...

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Section: See End Of Article For Authors' Affiliationsmentioning

confidence: 99%

Role of fibrin D-dimer testing in emergency medicine

Wakai

2003

Emergency Medicine Journal

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“…The dimeric D-domain is used as a marker of in-vivo fibrin formation [18]. In the clinical routine laboratory, the automated latex-enhanced light-scattering assay is the most commonly used type [19].…”

Section: Introductionmentioning

confidence: 99%

Comparison of six D-dimer assays for the detection of clinically suspected deep venous thrombosis of the lower extremities

Boeer

Siegmund²,

Schmidt³

et al. 2009

Blood Coagulation &Amp; Fibrinolysis

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Deep venous thrombosis is a common disease that may lead to life-threatening embolism of the lung as a common complication. Therefore, early diagnosis followed by sufficient treatment is necessary to decrease mortality of this disease. D-dimer testing is established as a standard to rule out deep venous thrombosis in selected patient groups. However, there is no standardization among D-dimer assays, and a periodical comparison of assay performance in a select patient group is indispensable. We evaluated six commonly used D-dimer assays for their assay performance in an outpatient cohort with clinically suspected deep venous thrombosis. Although area under the curve for these assays did not differ significantly (0.83-0.88), differences in sensitivity (90-100%) and specificity (10-40%) of the assays were detected. Alternative cut-offs were established, and these cut-offs could enhance assay performance in some cases. This points to the fact that the manufacturers should more regularly review studies on the performance of their respective assays to widen the data basis for their recommended cut-offs and increase assay performance.

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“…The first generation of D-dimer assays was thought to replace non-fibrin-specific degradation product assays performed with use of serum. Because the major proportion of high-molecular-weight fibrin complexes is incorporated into the clot during serum preparation, the analyte to be detected by the D-dimer assays is fibrin fragment D-dimer, mainly complexed with fragment E, 5,12 making serum D-dimer antigen an indicator of fibrin proteolysis.…”

Section: Development Of D-dimer Assay Systemsmentioning

confidence: 99%

Use of D-Dimer Assays in the Diagnosis of Venous Thrombosis

Dempfle¹

2000

Semin Thromb Hemost

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In the course of fibrin formation, the D-domains of adjacent fibrin molecules within the fibrin polymer are covalently linked by factor XIIIa, leading to the formation of a D-domain dimer. Proteolysis of this cross-linked fibrin generates fibrin fragments D-dimer and E as terminal products. Fragment D-dimer therefore is an indicator for the proteolysis of cross-linked fibrin, whereas the monomeric fragment D can stem from fibrinogen and non-cross-linked fibrin. Various monoclonal antibodies have been prepared that distinguish between fragments D-dimer and D and allow the detection of fibrin derivatives in the presence of fibrinogen. These anti-D-dimer-antibodies have been shown to react with fragment D-dimer, but also detect dimeric D-domains within larger fibrin compounds, including cross-linked fibrin complexes generated in an early phase of coagulation activation. Assay systems for D-dimer antigen therefore may uncover intravascular clot formation early, by detection of fibrin complexes, and after completion of clot formation, by the detection of proteolytic fragments released from the particulate clot. Various trials have shown that low concentrations of D-dimer antigen in the blood exclude recent venous thrombosis or pulmonary embolism. Elevated levels may be caused by venous thrombotic disease, but also by a variety of other conditions, leading to intra- or extravascular fibrin formation. Assay systems include manual immunoagglutination assays, immunofiltration assays, microtiter plate enzyme-linked immunosorbent assay (ELISA) systems, automated ELISA systems, and latex-enhanced photometric immunoassays. According to clinical studies, D-dimer assays may be the "first line" of technical screening in symptomatic outpatients with suspected venous thrombosis or pulmonary embolism, but further prospective management trials, and improved standardization of assay systems, are needed for the validation of this approach.

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Identification of D dimer-E complex in disseminated intravascular coagulation

Cited by 34 publications

References 13 publications

Role of fibrin D-dimer testing in emergency medicine

Role of fibrin D-dimer testing in emergency medicine

Comparison of six D-dimer assays for the detection of clinically suspected deep venous thrombosis of the lower extremities

Use of D-Dimer Assays in the Diagnosis of Venous Thrombosis

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