Analytical and clinical validation of a new point-of-care testing system for determination of D-Dimer in human blood.

D-Dimer testing is used for exclusion of deep venous thrombosis (DVT). AQT90 FLEX D-Dimer (AQT D-Dimer) is a novel time-resolved fluorescence based point-of-care test for quantification of D-Dimer in whole blood or plasma. Presently we have determined the analytical and clinical performance of AQT D-Dimer and compared it with four routine D-Dimer assays. The within-run CV of AQT D-Dimer was 3.8-7.2% and the between-run CV was 5.7- 9.7%. Excellent agreement was found between the D-Dimer concentrations recorded in citrate-, heparin- and EDTA stabilised blood. The plasma concentration of D-Dimer was determined with AQT D-Dimer, AxSYM, Biopool Auto-Dimer, STA-Liatest and Vidas New in 170 consecutive patients suspected for DVT. Phlebograms were positive in 64 patients (22 distal, 42 proximal). ROC-curves (ROC), the negative and positive predictive values (NPV, PPV), the sensitivity and specificity of the tests were compared. The area under ROC was comparable for all tests. NPV for all DVT was 87-88%, the sensitivity was 88-92% and the PPV was 45-55%. For proximal DVT the NPV and sensitivity were 100% for all tests, whereas the PPV was 37-48%. For distal DVT we obtained a NPV of 87-88%. The sensitivity was 64-77%, the PPV was 19-24% whereas a specificity of 32-58% was observed. The AQT D-Dimer demonstrates excellent analytical and diagnostic performance. The test is rapidly performed and the measuring range of the assay is wide. The NPV, PPV, specificity, sensitivity and AUC of AQT D-Dimer for both proximal and distal DVT are comparable to routine D-Dimer assays.

[1]  Herbert L. Abrams,et al.  Abrams angiography : vascular and interventional radiology , 1983 .

[2]  B. Lämmle,et al.  Usefulness of the D‐dimer/fibrinogen ratio to predict deep venous thrombosis , 2005, Journal of thrombosis and haemostasis : JTH.

[3]  K. Jochmans,et al.  Diagnostic accuracy of the Triage D-dimer test for exclusion of venous thromboembolism in outpatients. , 2008, Thrombosis research.

[4]  E. DeLong,et al.  Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. , 1988, Biometrics.

[5]  A. Akobeng,et al.  Understanding diagnostic tests 3: receiver operating characteristic curves , 2007, Acta paediatrica.

[6]  C. Legnani,et al.  A new rapid bedside assay for quantitative testing of D-Dimer (Cardiac D-Dimer) in the diagnostic work-up for deep vein thrombosis. , 2003, Thrombosis research.

[7]  T. Lindahl,et al.  Normal D-dimer concentration is a common finding in symptomatic outpatients with distal deep vein thrombosis , 2005, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[8]  E. M. Cott.  Point-of-care testing in coagulation. , 2009 .

[9]  P. Sandset,et al.  Validation of a new D-dimer microparticle enzyme immunoassay (AxSYM D-Dimer) in patients with suspected pulmonary embolism (PE). , 2007, Thrombosis research.

[10]  K. Valji,et al.  Vascular and Interventional Radiology , 1999 .

[11]  M. Huisman,et al.  Sensitivity and specificity of a quantitative point of care D-dimer assay using heparinized whole blood, in patients with clinically suspected deep vein thrombosis , 2006, Thrombosis and Haemostasis.

[12]  N. Shah,et al.  A systematic review of the accuracy of ultrasound in the diagnosis of deep venous thrombosis in asymptomatic patients , 2004, Thrombosis and Haemostasis.

[13]  J. Jespersen,et al.  Lupus anticoagulant is significantly associated with inflammatory reactions in patients with suspected deep vein thrombosis , 2007, Scandinavian journal of clinical and laboratory investigation.

[14]  E. Minar,et al.  Multicentre evaluation of a new point-of-care test for the quantitative determination of D-dimer. , 2001, Clinica chimica acta; international journal of clinical chemistry.

[15]  H R Büller,et al.  Diagnostic accuracy of D‐dimer test for exclusion of venous thromboembolism: a systematic review , 2007, Journal of thrombosis and haemostasis : JTH.

[16]  W. Bablok,et al.  A New Biometrical Procedure for Testing the Equality of Measurements from Two Different Analytical Methods. Application of linear regression procedures for method comparison studies in Clinical Chemistry, Part I , 1983, Journal of clinical chemistry and clinical biochemistry. Zeitschrift fur klinische Chemie und klinische Biochemie.

[17]  N. Perkins,et al.  The inconsistency of "optimal" cutpoints obtained using two criteria based on the receiver operating characteristic curve. , 2006, American journal of epidemiology.

[18]  Mark Stevenson,et al.  Measurement of the clinical and cost-effectiveness of non-invasive diagnostic testing strategies for deep vein thrombosis. , 2006, Health technology assessment.

[19]  K. Oniszh,et al.  Accuracy of compression ultrasound in screening for deep venous thrombosis in acutely ill medical patients , 2007, Thrombosis and Haemostasis.

[20]  J. Hirsh,et al.  Accuracy of Ultrasound for the Diagnosis of Deep Venous Thrombosis in Asymptomatic Patients after Orthopedic Surgery , 1995, Annals of Internal Medicine.

[21]  J. Philbrick,et al.  The d-dimer test for deep venous thrombosis: gold standards and bias in negative predictive value. , 2003, Clinical chemistry.

[22]  William A Ghali,et al.  d-Dimer for the Exclusion of Acute Venous Thrombosis and Pulmonary Embolism , 2004, Annals of Internal Medicine.

[23]  K. Forbes,et al.  The use of power Doppler ultrasound in the diagnosis of isolated deep venous thrombosis of the calf. , 1998, Clinical radiology.

[24]  F. Vitzthum,et al.  Factor VII-activating protease in patients with acute deep venous thrombosis. , 2008, Thrombosis research.

[25]  B. Woodhams,et al.  Stability of coagulation proteins in frozen plasma , 2001, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[26]  Martin W. Bunder,et al.  The inconsistency of , 1976, Journal of Symbolic Logic.

[27]  M. Borggrefe,et al.  Point of care coagulation tests in critically ill patients. , 2008, Seminars in thrombosis and hemostasis.

[28]  B. Reiser,et al.  Estimation of the Youden Index and its Associated Cutoff Point , 2005, Biometrical journal. Biometrische Zeitschrift.

[29]  J. Jespersen,et al.  Tissue factor pathway inhibitor relates to fibrin degradation in patients with acute deep venous thrombosis , 2008, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[30]  M. Siadaty,et al.  D-dimer testing for deep venous thrombosis: a metaanalysis. , 2004, Clinical chemistry.

[31]  A J Sutton,et al.  Variation in the diagnostic performance of D-dimer for suspected deep vein thrombosis. , 2005, QJM : monthly journal of the Association of Physicians.

[32]  K J M Janssen,et al.  Excluding venous thromboembolism using point of care D-dimer tests in outpatients: a diagnostic meta-analysis , 2009, BMJ : British Medical Journal.