Accuracy of D‐dimer/fibrinogen ratio to predict pulmonary embolism: a prospective diagnostic study – reply to a rebuttal

Abstract

Calvo‐Romero investigated functional fibrinogen levels and a semiquantitative latex agglutination D‐dimer test in a study of 40 Emergency Department patients with deep vein thrombosis (DVT) [1Calvo‐Romero JM. Accuracy of D‐dimer/fibrinogen ratio to predict pulmonary embolism: a prospective diagnostic study – a rebuttal. J Thromb Haemost 2004; 2: 1862–3.Google Scholar]. The main findings were that (i) fibrinogen levels were similar in eight patients with a negative and 32 with a positive D‐dimer test, and (ii) fibrinogen levels were not different between 19 patients with concomitant DVT and pulmonary embolism (PE) and 21 patients with ‘isolated’ DVT. Unfortunately, sensitivity of the semiquantitative latex agglutination D‐dimer assay for DVT is only 78%[95% confidence interval (CI) 69, 87][2Stein P.D. Hull R.D. Patel K.C. Olson R.E. Ghali W.A. Brant R. Biel R.K. Bharadia V. Kalra N.K. D‐dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review.Ann Intern Med. 2004; 140: 589-602Crossref PubMed Google Scholar]. In contrast, the rapid quantitative ELISA D‐dimer assay has a sensitivity for DVT of 96% (95% CI 91, 100) [1Calvo‐Romero JM. Accuracy of D‐dimer/fibrinogen ratio to predict pulmonary embolism: a prospective diagnostic study – a rebuttal. J Thromb Haemost 2004; 2: 1862–3.Google Scholar]. Diagnosis of venous thromboembolism remains challenging despite the availability of sophisticated imaging tests. There is no mention of the diagnostic strategy used in this study. PE imaging tests were not performed in the entire cohort but in patients with symptoms compatible with PE. Although approximately half of the DVT patients have silent PE [3Meignan M. Rosso J. Gauthier H. Brunengo F. Claudel S. Sagnard L. D'Azemar P. Simonneau G. Charbonnier B. Systematic lung scans reveal a high frequency of silent pulmonary embolism in patients with proximal deep venous thrombosis.Arch Intern Med. 2000; 160: 145-6Crossref PubMed Google Scholar], in the present study, patients with DVT and no symptoms of PE were classified as ‘isolated’ DVT patients. It also remains unclear whether patients with massive PE were included. Not surprisingly, the study results suggest that patients with concomitant DVT and PE cannot be separated from DVT patients without PE symptoms based on test results of a semiquantitative D‐dimer assay and a quantitative fibrinogen assay. However, no conclusion can be drawn from this study regarding the diagnostic utility of fibrinogen in DVT since there was no control group of patients with suspected but excluded DVT. In addition, the study results do not allow a conclusion regarding D‐dimer and fibrinogen levels in acute PE because (i) the sample size was too small, (ii) the PE patients included were not representative of the entire PE population, and (iii) no quantitative D‐dimer test was used. In our controlled study of 191 Emergency Department patients with suspected PE, a consumption phenomenon (low fibrinogen and exceedingly high ELISA D‐dimer levels) was particularly found in patients with massive PE and a high pulmonary occlusion rate as assessed by chest computed tomography [4Kucher N. Kohler H.P. Dornhofer T. Wallmann D. Lammle B. Accuracy of D‐dimer/fibrinogen ratio to predict pulmonary embolism: a prospective diagnostic study.J Thromb Haemost. 2003; 1: 708-13Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 5Kucher N. Kohler H.P. Doernhoefer T. Wallmann D. Laemmle B. Potential role of D‐dimer to rule in pulmonary embolism: reply to a rebuttal.J Thromb Haemost. 2004; 2: 369-70Abstract Full Text Full Text PDF Google Scholar]. Conversely, fibrinogen levels were mostly in the normal range and D‐dimer levels were only moderately elevated in patients with non‐massive PE and a low pulmonary occlusion rate. There was no consumption coagulopathy in patients with suspected but excluded PE. By receiver operating characteristic analysis, the D‐dimer/fibrinogen ratio had a higher specificity for predicting PE than the ELISA D‐dimer test alone. Further studies are needed to confirm that the D‐dimer/fibrinogen ratio is useful to rule in PE.