Comparison of Three D-Dimer Assays for the Diagnosis of DVT: ELISA, Latex and an Immunofiltration Assay (NycoCard D-Dimer)

Dale, S.; Gogstad, Geir O.; Brosstad, Frank; Godal, H. C.; Holtlund, Jostein; Mørk, Einar; Brandsnes, Øystein; Borch, S. M.

doi:10.1055/s-0038-1642428

Cited by 83 publications

(56 citation statements)

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“…35 Immunofiltration tests yield results within 2 minutes, allowing for prompt reporting and clinical management. 36 Automated techniques that quantitate latex agglutination rates also have excellent sensitivity and have been demonstrated to maintain good correlation with ELISA. 37 ELISA and latex turbidimetric methods have both been approved by the US Food and Drug Administration for the exclusion of venous thromboembolism and are used worldwide for this purpose.…”

Section: D-dimer Laboratory Assaysmentioning

confidence: 99%

D-dimer antigen: current concepts and future prospects

Adam

Key

Greenberg

2009

Blood

543

453

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The D-dimer antigen is a unique marker of fibrin degradation that is formed by the sequential action of 3 enzymes: thrombin, factor XIIIa, and plasmin. First, thrombin cleaves fibrinogen producing fibrin monomers, which polymerize and serve as a template for factor XIIIa and plasmin formation. Second, thrombin activates plasma factor XIII bound to fibrin polymers to produce the active transglutaminase, factor XIIIa. Factor XIIIa catalyzes the formation of covalent bonds between D-domains in the polymerized fibrin. Finally, plasmin degrades the crosslinked fibrin to release fibrin degradation products and expose the D-dimer antigen. D-dimer antigen can exist on fibrin degradation products derived from soluble fibrin before its incorporation into a fibrin gel, or after the fibrin clot has IntroductionFibrinogen is a soluble plasma glycoprotein that is transformed into highly self-adhesive fibrin monomers after thrombin cleavage. 1 A detailed overview of the process of fibrin formation was recently published. 2 In brief, in the first step of D-dimer formation, thrombin cleavage exposes a previously cryptic polymerization site on fibrinogen that promotes the binding of either another fibrinogen or a monomeric fibrin molecule. 3 Fibrin monomers then bind to one another in an overlapping manner to form 2 molecule thick protofibrils ( Figure 1). 4,5 Plasma remains fluid until 25% to 30% of plasma fibrinogen is cleaved by thrombin, 6 allowing time for fibrin to polymerize while simultaneously promoting thrombin activation of plasma factor XIII. 7 Thrombin remains associated with fibrin, 8 and as additional fibrin molecules polymerize, it activates plasma factor XIII bound to fibrinogen. 9 The complex between soluble fibrin polymers, thrombin, and plasma factor XIII promotes the formation of factor XIIIa before a fibrin gel is detected. 6 In the second step of D-dimer formation, factor XIIIa covalently cross links fibrin monomers via intermolecular isopeptide bonds formed between lysine and glutamine residues within the soluble protofibrils and the insoluble fibrin gel. 10 D-dimer antigen remains undetectable until it is released from crosslinked fibrin by the action of plasmin. In the final step of D-dimer formation, plasmin formed on the fibrin surface by plasminogen activation cleaves substrate fibrin at specific sites ( Figure 1). 11 Fibrin degradation products are produced in a wide variety of molecular weights, including the terminal degradation products of crosslinked fibrin containing D-dimer and fragment E complex (Figure 1). 12,13 It is uncommon to detect circulating terminal fibrin degradation products (D-dimer-E complex) in human plasma, whereas soluble high-molecular-weight fragments that contain the "D-dimer antigen" are present in patients with DIC and other thrombotic disorders. 14 These fragments may be derived from soluble fibrin before it has been incorporated into a fibrin gel, or alternatively may be derived from high-molecular-weight complexes released from an insoluble clot (Figure 2). 15,16 "D-...

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Section: D-dimer Laboratory Assaysmentioning

confidence: 99%

D-dimer antigen: current concepts and future prospects

Adam

Key

Greenberg

2009

Blood

543

453

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“…ELISA has consistently shown high sensitivity: 98% (Dale et al, 1994), 96 . 8% (Bournameux et al, 1994) and negative predictive values: 95% (Dale et al, 1994) for the diagnosis of DVT. Low specificity for predicting DVT: 38% (Dale et al, 1994), 35 .…”

mentioning

confidence: 99%

“…Although accurate, ELISA is time consuming and is not a realistic choice for a screening test in an emergency or outpatient setting. Latex agglutination is faster but only has a sensitivity of 73% for the diagnosis of DVT (Dale et al, 1994), making it unsuitable as an exclusion test.NYCOCARD D-dimer (Nycomed Pharma AS, Norway) is an immunofiltration system. Preliminary results suggest that the sensitivity of the NycoCard system for D-dimer approaches that of ELISA.…”

mentioning

confidence: 99%

Comparison of immunofiltration assay of plasma D‐dimer with diagnostic imaging in deep vein thrombosis

Killick¹,

Pentek²,

Mercieca³

et al. 1997

Br J Haematol

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Summary. This prospective study was designed to assess the diagnostic sensitivity, specificity and negative predictive value of the NycoCard D-dimer plasma immunofiltration assay in patients with suspected deep vein thrombosis (DVT) confirmed by ultrasonography/venography. 84 medical patients were recruited: 43 patients (51%) had proven venous thrombosis, 33 by venography and 10 by ultrasonography. The sensitivity of NycoCard D-dimer in patients with DVT was 95 . 3%, the specificity was 22 . 0% and the negative predictive value was 81 . 8%. An algorithm including the NycoCard D-dimer test for the acute management of DVT is proposed. This would enable low-risk patients to be discharged early from hospital, without imaging or anticoagulant therapy.Keywords: deep vein thrombosis, D-dimer, diagnosis, laboratory tests.The lifetime risk of developing a DVT is approximately 2-5% (Davies & Tuddenham, 1987). Diagnosis and management of this condition therefore forms a substantial part of the acute workload in most hospitals.The clinical diagnosis of DVT is unreliable. The 'gold standard' for diagnosis is ascending radiographic venography, which has significant morbidity: local pain, allergic reactions to the contrast material and thrombosis induced by the procedure itself. In addition, the delay before a definitive result is known incurs extra cost if protective hospital admission and anticoagulation occur.D-dimer is a specific degradation product of cross-linked fibrin. Plasma concentration is raised in thromboembolism, reflecting fibrin formation and dissolution, so measurement of plasma D-dimer has a potential use in the diagnosis of DVT. Monoclonal antibodies against neoantigens exposed in the split products of fibrin allow direct plasma assay.Methods for testing D-dimer include ELISA, latex agglutination and immunofiltration. ELISA has consistently shown high sensitivity: 98% (Dale et al, 1994), 96 . 8% (Bournameux et al, 1994) and negative predictive values: 95% (Dale et al, 1994) for the diagnosis of DVT. Low specificity for predicting DVT: 38% (Dale et al, 1994), 35 . 2% (Bournameux et al, 1994 and positive predictive value: 54% (Dale et al, 1994), limits D-dimer to a test of exclusion only. Although accurate, ELISA is time consuming and is not a realistic choice for a screening test in an emergency or outpatient setting. Latex agglutination is faster but only has a sensitivity of 73% for the diagnosis of DVT (Dale et al, 1994), making it unsuitable as an exclusion test.NYCOCARD D-dimer (Nycomed Pharma AS, Norway) is an immunofiltration system. Preliminary results suggest that the sensitivity of the NycoCard system for D-dimer approaches that of ELISA. (Dale et al, 1994). The assay time is less than 2 min, so the test is suitable for use in acute care. PATIENTS AND METHODSThe study was designed as a double-blind prospective investigation of the use of the NycoCard D-dimer test in patients with suspected DVT. Entry criteria for the study population were medical inpatients or outpatients referred to the St Helier ...

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“…A very good profile of D-dimer was observed in the initial studies and evaluations (sensitivity and negative predictive value >95%) (15,37). However, recent investigation was less convincing.…”

Section: D-dimer Poc Assaysmentioning

confidence: 96%

»Point-of-Care« D-Dimer Testing

Antović¹

2010

Journal of Medical Biochemistry

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Kratak sadr`aj: Odre|ivanje D-dimera omogu}ava efikasno isklju~ivanje venskog tromboembolizima (VTE). Labo ratorijsko testiranje D-dimera prete`no se izvodi u centralizovanim laborato rijama u okviru bolnica, iako se ve}ina pacijenata kod kojih se sumnja na VTE javlja na pregled u ustanove primarne zdravstvene za{tite. Tako|e, skra}enje ukupnog trajanja laboratorijskog testiranja bi znatno pobolj{alo efikasnost u urgentnim centrima. Stoga bi uvo|e -nje brzog »Point of Care (POC)« D-dimer testa koji se lako izvodi, dovelo do pobolj{anja dijagnostike VTE u primarnoj zdravstvenoj za{titi kao i u urgentnim centrima, ali tako|e i u dijagnostici drugih te{kih klini~kih stanja (diseminovana intravaskularna koagulacija (DIK), aneurizma aorte) u kojima je D-dimer povi{en. Ve}ina dostupnih POC D-dimer testova ispunjava kriterijume za brzo i sigurno isklju~ivanje VTE-a. U na{em ispitivanju tri testa (Stratus, Pathfast i Cardiac) pokazala su karakteristike sli~ne D-dimer testu koji je u rutinskoj upotrebi u na{oj laboratoriji (Tinaquant).

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Comparison of Three D-Dimer Assays for the Diagnosis of DVT: ELISA, Latex and an Immunofiltration Assay (NycoCard D-Dimer)

Cited by 83 publications

References 24 publications

D-dimer antigen: current concepts and future prospects

D-dimer antigen: current concepts and future prospects

Comparison of immunofiltration assay of plasma D‐dimer with diagnostic imaging in deep vein thrombosis

»Point-of-Care« D-Dimer Testing

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