Plasma Measurement of D-Dimer as Diagnostic Aid in Suspected Venous Thromboembolism: An Overview

Summary

This paper reviews the published experience with plasma measurement of D-dimer (DD), a specific degradation product of crosslinked fibrin, in the diagnostic approach of venous thromboembolism (VTE). Pooling 11 studies (with weighting of the figures according to sample size) with a total of 1337 patients clinically suspected of deep venous thrombosis (DVT) (prevalence of DVT 35%) disclosed an average weighted sensitivity of 96.8% (95% CI: 95.2–98.4) and specificity of 35.2% (95% Cl: 32.0–38.4) for the presence of DVT when the ELISA technique was used. In 908 patients suspected of pulmonary embolism (PE) from 9 trials (prevalence of PE 38%), the ELISA technique was associated with a weighted sensitivity of 96.8% (95% Cl: 95.0–98.6) and specificity of 45.1% (95% Cl: 40.8–49.4) for the disease. Figures obtained with latex assays were definitely lower, precluding their use in the diagnostic approach of VTE.

These results show that a low concentration of plasma DD measured by the ELISA technique (usually less than 500 μg/1) might be used to rule out VTE in clinically suspected patients. Increased plasma concentrations are of no utility because of the low specificity of this test result.

The clinical usefulness of the DD ELISA test should now be assessed in management trials under routine conditions, in the frame of clinical decision-making diagnostic processes. Lastly, the promising data obtained in a small number of asymptomatic, postoperative patients at risk of VTE deserve confirmation before the test can be recommended for initial screening in thrombo-prophylactic trials.

• References

• 1 Kroneman R, Nieuwenhuizen W, Knot EA R. Monoclonal antibody-based plasma assays for fibrin(ogen) and derivatives, and their clinical relevance. Blood Coag Fibrinol 1990; 1: 91-111
• 2 Biiller HR, Lensing AW A, Hirsh J, ten Cate JW. Deep vein thrombosis: new non-invasive diagnostic tests. Thromb Haemostas 1991; 66: 133-7
• 3 Heaton DC, Billings JD, Hickton CM. Assessment of D dimer assays for the diagnosis of deep vein thrombosis. J Lab Clin Med 1987; 110: 588-91
• 4 Rowbotham BJ, Carroll P, Whitaker AN, Bunce IH, Cobcroft RG, Elms MJ, Masci PP, Bundesen PG, Rylatt DB, Webber AJ. Measurement of crosslinked fibrin derivatives – Use in the diagnosis of venous thrombosis. Thromb Haemostas 1987; 57: 59-61
• 5 Ott P, Astrup L, Hartving Jensen R, Nyeland B, Pedersen B. Assessment of D-dimer in plasma: diagnostic value in suspected deep venous thrombosis of the leg. Acta Med Scand 1988; 224: 263-7
• 6 Bounameaux H, Schneider PA, Reber G, de Moerloose P, Krahenbuhl B. Measurement of plasma D-dimer for diagnosis of deep venous thrombosis. Am J Clin Pathol 1989; 91: 82-5
• 7 Chapman CS, Akhtar N, Campbell S, Miles K, O’Connor J, Mitchell VE. The use of D-Dimer assay by enzyme immunoassay and latex agglutination techniques in the diagnosis of deep vein thrombosis. Clin Lab Haemat 1990; 12: 37-42
• 8 Mossaz A, Gandrille S, Vitoux JF, Abdoucheli-Baudot N, Aiach M, Fiessinger JN. Valcur des D-dimères dans le diagnostic en urgence des thromboses veincuses. Presse méd 1990; 19: 1055
• 9 van Bergen PFMM, Knot EA R, Jonker JJ C, de Boer AC, de Maat MP M. Is quantitative determination of fibrin(ogcn) degradation products and thrombin-antithrombin III complexes useful to diagnose deep venous thrombosis in outpatients?. Thromb Haemostas 1989; 62: 1043-5
• 10 Elias A, Aillaud MF, Roul C, Villain Ph, Serradimigni A, Juhan-Vague I. Assessment of D-dimer measurement by ELISA or latex methods in deep vein thrombosis diagnosed by ultrasonic duplex scanning. Fibrinolysis 1990; 4: 237-40
• 11 Boneu B, Bes G, Pelzcr H, Sié P, Boccalon H. D-dimers, thrombin-antithrombin III complexes and prothrombin fragments 1+2: diagnostic value in clinically suspected deep vein thrombosis. Thromb Haemostas 1991; 65: 28-32
• 12 Chang-Liem GS, Lustermans FA T, van Wersch JW J. Comparison of the appropriateness of the latex and Elisa D-dimer determination for the diagnosis of deep venous thrombosis. Haemostasis 1991; 21: 106-10
• 13 Heijboer H, Ginsberg JS, Biiller HR, Lensing AW A, Colly LP, ten Cate JW. The use of the D-dimer test in combination with non-invasive testing alone for the diagnosis of deep-vein thrombosis. Thromb Haemostas 1992; 67: 510-13
• 14 Bounameaux H, Khabiri E, Huber O, Schneider PA, Didicr D, de Moerloose P, Reber G. Value of liquid crystal contact thermography and plasma level of D-dimer for screening of deep venous thrombosis following general abdominal surgery. Thromb Haemostas 1992; 67: 603-6
• 15 Rowbotham BJ, Whitaker AN, Harrison J, Murtaugh P, Reasbeck P, Bowie EJ W. Measurement of crosslinked fibrin derivatives in patients undergoing abdominal surgery: use in the diagnosis of postoperative venous thrombosis. Blood Coag Fibrinol 1992; 3: 25-31
• 16 Lensing AW A, Hirsh J. ¹²⁵I-Fibrinogen leg scanning: reassessment of its role for the diagnosis of venous thrombosis in post-operative patients. Thromb Haemostas 1993; 69: 2-7
• 17 Alderson PO, Martin EC. Pulmonary embolism: diagnosis with multiple imaging modalities. Radiology 1987; 167: 297-312
• 18 Hull RD, Raskob GE, Coates G, Panju AA. Clinical validity of a normal perfusion lung scan in patients with suspected pulmonary embolism. Chest 1990; 97: 23-6
• 19 Kipper SM, Moser KM, Kortman KE, Ashburn WL. Longterm follow-up of patients with suspected pulmonary embolism and a normal lung scan. Chest 1982; 82: 411-25
• 20 The PIOPED Investigators.. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990; 263: 2653-9
• 21 Bounameaux H, Cirafici P, de Moerloose P, Slosman D, Reber G, Unger PF. Measurement of D-Dimer in plasma as diagnostic aid in suspected pulmonary embolism. Lancet 1991; 337: 196-200
• 22 Bounameaux H, Slosman D, de Moerloose P, Reber G. Diagnostic value of plasma D-dimer in suspected pulmonary embolism. Lancet 1988; II: 628-9
• 23 Goldhaber SZ, Vaughan DE, Tumeh SS, Loscalzo J. Utility of cross-linked fibrin degradation products in the diagnosis of pulmonary embolism. Am Heart J 1989; 116: 505-8
• 24 Bounameaux H, Schneider PA, Slosman D, de Moerloose P, Reber G. Plasma D-dimer in suspected pulmonary embolism: a comparison with pulmonary angiography and ventilation-perfusion scintigraphy. Blood Coag Fibrinol 1990; 1: 577-9
• 25 Bounameaux H, Slosman D, de Moerloose P, Reber G. Laboratory diagnosis of pulmonary embolism: value of increased levels of plasma D-dimer and thrombin-antithrombin III complexes. Biomed Pharmacother 1989; 43: 385-8
• 26 Rowbotham BJ, Egerton-Vernon J, Whitaker AN, Elms MJ, Bunce IH. Plasma cross linked fribrin degradation products in pulmonary embolism. Thorax 1990; 45: 684-7
• 27 Lichey J, Reschofski I, Dissmann T, Priesnitz M, Hoffmann M, Lode H. Fibrin degradation product D-dimer in the diagnosis of pulmonary embolism. Klin Wschr 1991; 69: 522-6
• 28 Demers C, Ginsberg JS, Gohnston M, Brill-Edwards P, Panju A. D-dimer and thrombin-antithrombin III complexes in patients with clinically suspected pulmonary embolism. Thromb Haemostas 1992; 67: 408-12
• 29 Goldhaber SZ, Simons GR, Elliott CG, Haire WD, Toltzis R, Blacklow SC, Doolittle MH, Weinberg DS. Quantitative plasma D-Dimer levels among patients undergoing pulmonary angiography for suspected pulmonary embolism. JAMA. 1993. (in press)
• 30 van Beek EJ R, van den Ende B, Berckmans RJ, van der Heide Y, Brandjes DP M, Sturk A, ten Cate JW. A comparative analysis of D-Dimer assays in patients with clinically suspected pulmonary embolism. Thromb Haemostas 1993; 70: 408-13
• 31 Leitha T, Speiser W, Dudzak R. Pulmonary embolism. Efficacy of D-dimer and thrombin-antithrombin III complex determinations as screening tests before lung scanning. Chest 1991; 100: 1536-41
• 32 de Boer WA, de Haan MA, Huisman JW, Klaassen CH L. D-dimer latex assay as screening method in suspected deep venous thrombosis of the leg. A clinical study and review of the literature. Neth J Med 1991; 38: 65-9
• 33 Lesprit P, Gepner P, Piette AM, de Tovar G, Filiole M, Didon D, Chapman A. Phlébites profondes des membres inférieurs. Intérêt diagnostique du dosage des D-dimères. Presse méd 1991; 20: 1927-9
• 34 Carter CJ, Doyle DL, Dawson N, Fowler S, Devine DV. Investigations into the clinical utility of latex D-dimer in the diagnosis of deep venous thrombosis. Thromb Ilaemustas 1993; 69: 8-11
• 35 Harrison KA, Haire WD, Pappas AA, Purnell GL, Palmer S, Holdeman KP, Fink LM, Dalrymple GV. Plasma D-dimer: a useful tool for evaluating suspected pulmonary embolism. J Nucl Med 1993; 34: 896-8
• 36 Raimondi P, Bongard O, de Moerloose P, Reber G, Waldvogel F, Bounameaux H. D-Dimer plasma concentration in various clinical conditions: Implication for the use of this test in the diagnostic approach of venous thromboembolism. Thromb Res 1993; 69: 125-30
• 37 Reber G, de Moerloose P, Minazio P, Bounameaux H. Comparison of two new latex assays for D-dimer with an ELISA method. Thromb Haemostas 1993; 69: 838 (abstract)
• 38 Cadroy Y, Pierrejean D, Fontan B, Sié P, Boneu B. Influence of aging on the activity of the hemostasis system: prothrombin fragment 1+2, thrombin-antithrombin III complexes and D-dimers in 80 healthy subjects with age ranging from 20 to 94 years. Nouv Rev Fr Hematol 1992; 34: 43-6
• 39 Sox HC, Blatt MA, Higgins MC, Marton KI. Medical decision making. Butterworths, Boston. 1988: pp. 67-101
• 40 Perrier A, Bounameaux H, Morabia A, de Moerloose P, Unger PF, Slosman D, Junod AF. Contribution of plasma D-dimer and lower limb venous ultrasound to the diagnosis of pulmonary embolism: a decision analysis. Am Heart J (in press);