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

Abstract

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 ...

Exclusion of Deep Venous Thrombosis with D-Dimer Testing

“…With regard to sensitivity our result for INSTANT I.A. is consistent with that of other investigations (12,15,23,(26)(27)(28), while for Nyco-Card our result is slightly better than that of most other studies (12,15,18,23,26,(29)(30)(31). Reported specificities for DVT and PE vary widely for INSTANT I.A (19-93%) as well as for NycoCard (0-80%), which might be caused, at least in part, by differences in composition of the population evaluated.…”

Combined use of rapid D-dimer testing and estimation of clinical probability in the diagnosis of deep vein thrombosis: systematic review

“…After review of titles and abstracts we retrieved 84 for detailed examination (figure). Sixty nine did not meet our inclusion criteria because they were letters, editorials, or reviews25 – 38; did not evaluate both a D-dimer assay and a clinical probability tool39 – 78; did not categorise patients into low risk, moderate or intermediate risk, and high risk for deep vein thrombosis15; were not prospective79 – 81; included only inpatients or did not allow for separate analysis of outpatients82 – 88; included data that did not allow separate analysis of patients with a diagnosis of deep vein thrombosis and pulmonary embolism89; or had follow up of less than three months' duration 90 – 92…”

D-Dimer Testing for Deep Venous Thrombosis: A Metaanalysis

“…Twenty-three studies were designated Level 1, and their results form the basis for this review (14 -36 ). We excluded those studies that failed to adequately describe the method of patient selection (Standard 3) (37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51), studied a population that did not represent the full spectrum of disease (Standard 6) (40,42,46,52,53 ), or based the performance of the reference standard on the results of the D-dimer testing (Standard 7) (40, 41, 44, 46, 48, 51, 52, 54 -56 ).…”