Evaluation of a Soluble Fibrin Assay in Patients with Suspected Deep Vein Thrombosis

Summary

Background. The objective of this study was to determine the clinical utility of an enzyme immunoassay (HIA) for soluble fibrin in patients with clinically suspected deep vein thrombosis (DVT).

Methods and Results. 101 unselected patients with clinically suspected DVT underwent blood sampling for measurement of plasma levels of soluble fibrin, and objective testing for DVT. According to results of the objective tests, patients were classified as DVT-positive (n = 34) or DVT-negative (n = 67). Using different cut-points of soluble fibrin results, the sensitivities, specificities, positive and negative predictive values of the soluble fibrin assay were calculated. A soluble fibrin result of ≤0.75 mg/ml showed a sensitivity and negative predictive value of 100%, and a specificity of 17.9% for DVT, a soluble fibrin result of ≤ 1.40 mg/ml showed a sensitivity of 91.2% and a negative predictive value of 93.6%, and a specificity of 65.7% for DVT, whereas a soluble fibrin result of ≤ 8.0 mg/ml showed a specificity and positive predicive value of 100% for DVT.

Conclusions. This study demonstrates that the soluble fibrin assay used in the study has potential clinical utility as a diagnostic test in patients with clinically suspected DVT and supports further evaluation of this assay.

• References

• 1 Wheeler HB, Anderson FA. Diagnostic approaches for deep vein thrombosis. Chest 1986; 89: 407-412
• 2 Hull RD, Carter CJ, Jay RM, Ockelford PA, Hirsh J, Turpie AG G, Zielin- sky P, Gent M, Powers PJ. The diagnosis of acute, recurrent, deep-vein thrombosis: A diagnostic challenge. Circulation 1983; 67: 901-906
• 3 Heijboer H, Jongbloets MM, Buller HR, Lensing AW A, ten Cate JW. Clinical utility of real-time for diagnostic management of patients with recurrent venous thrombosis. Acta Radiologica 1992; 33: 297-300
• 4 Cronan JJ, Leen V. Recurrent deep venous thrombosis: Limitations of US¹ . Radiology 1989; 170: 739-742
• 5 Mantoni M. Deep venous thrombosis: Longitudinal study with Duplex US¹ . Radiology 1991; 179: 271-273
• 6 Jay RM, Hull PD, Hirsh J, Carter CJ, Ockelford PA, Buller HR, Turpie AG G. Outcome of abnormal impedance plethysmography results in patients with proximal vein thrombosis: Frequency of return to normal. Thromb Res 1984; 36: 259-263
• 7 Huisman MV, Buller HR, ten Cate JW, Heijermans HS F, van der Laan J, van Maanen DJ. Management of clinically suspected acute venous thrombosis in outpatients with serial impedance plethysmography in a community hospital setting. Arch Intern med 1989; 149: 511-513
• 8 Hull RD, Hirsh J, Carter CJ, Jay RM, Ockelford PA, Buller HR, Turpie AG G, Powers P, Kinch D, Dodd PE, Gill GJ, Leclerc JR, Gent M. Diagnostic efficacy of impedance plethysmography for clinically suspected deep-vein thrombosis: a randomized trial. Ann Intern Med 1985; 102: 21-28
• 9 Huisman MV, Buller HR, ten Cate JW, Vreeken J. Serial impedance plethysmography for suspected deep venous thrombosis in outpatients. N Engl J Med 1986; 314: 823-828
• 10 Heijboer H, Buller HR, Lensing AW A, Turpie AG G, Colly LP, ten Cate JW. A Comparison of real time with impedance plethysmography for the diagnosis of deep-vein thrombosis in symptomatic outpatients. N Engl J Med 1993; 329: 1365-1369
• 11 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: 385-388
• 12 Bridey F, Philipotteau C, Dreyfus M, Simonneau G. Plasma D-Dimer and pulmonary embolism. Lancet 1989; 1: 791-792
• 13 Speiser W, Leitha T, Duczak R, Lechner K. Letter to the editor,. Lancet 1989; 1: 792
• 14 Goldhaber SZ, Vaughan DE, Tumeh SS, Loscalzo J. Utility of cross-linked fibrin degradation products in the diagnosis of pulmonary embolism. Am Heart J 1988; 116: 505-508
• 15 Bounameaux H, Cirafici P, DeMoerloose P, Schneider PA, Slosman D, Reber G, Unger PF. Measurement of D-dimer as diagnostic aid in suspected pulmonary embolism. Lancet 1991; 337: 196-200
• 16 Pelzer H, Schwarz A, Heimburger N. Determination of human thrombin- antithrombin III complex in plasma with an enzymelinked immunosorbent assay. Thromb Haemost 1988; 59: 101-106
• 17 Rowbotham BJ, Carrol P, Whitaker AN, Bunce IH, Colcroft RG, Elms ME, Masci PP, Bundesen PG, Rylatt DB, Webber AJ. Measurement of cross- linked fibrin derivates-use in the diagnostic of venous thrombosis. Thromb Haemost 1987; 57: 59-61
• 18 Bounameaux H, Schneider PA, Reber G, De Moerloose P, Krahenbuhl B. Measurement of plasma D-Dimer for diagnosis of deep venous thrombosis. AJCP 1989; 91: 82-85
• 19 Demers C, Ginsberg JS, Johnston M, Brill-Edwards P, Panju A. D-dimer and thrombin-antithrombin III complexes in patients with clinically suspected pulmonary embolism. Thromb Haemost 1992; 67: 408-412
• 20 Heaton DC, Billings JD, Hickton CM. Assessment of D-dimer assays for the diagnosis of deep venous thrombosis. J Lab Clin Med 1987; 110: 588-591
• 21 Ginsberg JS, Brill-Edwards P, Demers C, Donovan D, Panju A. D-dimer in patients with clinically suspected pulmonary embolism. Chest 1993; 104: 1679-1684
• 22 Heijboer H, Ginsberg JS, Buller HR, Lensing AW A, Colly LP, ten Cate JW. The use of the D-dimer test in combination with non-invasive testing versus serial non-invasive testing alone for the diagnosis of deep-vein thrombosis. Thromb Haemost 1992; 67: 510-513
• 23 Brenner B, Pery M, Lanir N, Jabbarin A, Kraftori JK, Gaitini D, Rylatt D. Application of SimpliRED D-dimer in the diagnosis of deep vein thrombosis. Thromb Haemost 1993; 69: 832 (1042a)
• 24 Shaukat N, Rowlands DJ, Cotter L, Walker MG, Douglas JT. The specificity and sensitivity of various Elisa methods for fibrin degradation products in the diagnosis of arterial and venous thrombosis. Thromb Haemost 1993; 69: 839 (1065a)
• 25 Bounameaux H, de Moerloose P, Perrier A, Reber G. Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost 1994; 71: 1-6
• 26 John MA, Elms MJ, O’Reilly EJ, Rylatt DB, Bundesen PG, Hillyard CJ. The simpliRED D-dimer test: a novel assay for the detection of cross- linked fibrin degradation products in whole blood. Thromb Res 1990; 58: 273-281
• 27 Ginsberg JS, Wells PS, Brill-Edwards P, Donovan D, Panju AA, Patel MA. Application of a novel and rapid whole blood assay for D-dimer in patients with clinically suspected pulmonary embolism Thromb Haemost. 1995; 73: 35-38
• 28 Wells PS, Brill-Edwards P, Stevens P, Panju A, Patel A, Douketis J, Massicotte MP, Hirsh J, Weitz JI, Kearon C, Ginsberg JS. A novel and rapid whole blood assay for D-dimer in patients with clinically suspected deep vein thrombosis. Circulation. (in press)
• 29 Prins MH, Hirsh J. A critical review of the evidence supporting a relationship between impaired fibrinolytic activity and venous thromboembolism. Arch Intern Med 1993; 151: 1721-1731
• 30 Gaffney P. The occurrence and clinical relevance of fibrin fragments in blood. Ann NY Acad Sc 1983; 408: 407-422
• 31 Ridker PW, Vaughan DE, Stampfer MJ, Manson JE, Shen C, Newcomer LM, Goldhaber SZ, Hennekens CH. Baseline fibrinolytic state and the risk of future venous thrombosis. A prospective study of endogenous tissue- type plasminogen activator and plasminogen activator inhibitor Circulation 1992; 85 (05) 1822-1827
• 32 Levi M, Lensing AW A, Buller HR, Prandoni P, Dooijewaard G, Cuppini S, ten Cate JW. Deep vein thrombosis and fibrinolysis. Defective urokinase type plasminogen activator release Thromb Haemost 1991; 66 (04) 426-429
• 33 Grimaudo V, Bachmann F, Hauert J, Christe MA, Kruithof EK O. Hypo- fibrinolysis in patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism. Thromb Haemost 1992; 67 (04) 397-401
• 34 Harbourne T, O’Brien D, Nicolaides AN. Fibrinolytic activity in patients with idiopathic and secondary deep vein thrombosis. Thromb Res 1991; 64: 543-550
• 35 Sasaki T, Page IH, Shainoff JR. Soluble complex of fibrinogen and fibrin. Science 1966; 152: 1069
• 36 Alkajersig N, Fletcher AP. Formation of soluble fibrin oligomers in purified system and in plasma. Biochem J 1983; 213: 75
• 37 Niewiarowski S, Gurewich V. Laboratory identification of intravascular coagulation. The serial dilution protamine sulfate test for the detection of fibrin monomer and FDP J Lab Clin Med 1971; 77: 665
• 38 Rabinov K, Paulin S. Roentgen diagnosis of venous thrombosis in the leg. Arch Surg 1972; 104: 134-144
• 39 Lensing AW A, Prandoni P, Brandjes DP M, Huisman PM, Vigo M, Tomasella G, Krekt J, ten Cate JW, Huisman MV, Buller HR. Detection of deep-vein thrombosis by real-time B-mode ultrasonography. N Engl J Med 1989; 320: 342-345
• 40 Simels DL, Samsas GP, Matchar DB. Likelihood ratios with confidence: sample size estimation for diagnostic test studies. J Clin Epidemiol 1991; 44: 763-770
• 41 Dempfle CE, Dolmann M, Lill H, Muhlhofer W, Dessauer A, Heene DL. Activation parameters of blood coagulation in medical and surgical patients developing DVT: evaluation of a new fibrin monomer ELISA. Thromb Haemost 1993; 69: 1004 (1649a)
• 42 Hansson PO, Eriksson H, Eriksson E, Jagenburg R, Lukes P, Risberg B. Can laboratory testing improve screening strategies for deep vein thrombosis at an emergency unit;. J Int Med 1994; 235: 143-151