The role of fibrin monomers in optimizing the diagnostic work-up of deep vein thrombosis.
ABSTRACT Despite the use of a clinical score and D-dimers to exclude deep vein thrombosis (DVT), the majority of patients still need repeated ultrasound (US). The aim of the study was to investigate whether fibrin monomers (FMs), as markers of thrombin generation, have additional value in the diagnosis of DVT. This is a posthoc analysis of 464 outpatients, participants in a management study using D-dimers (Tina-Quant and a clinical score in the exclusion of DVT. Two new FM assays (Auto LIA-FM and IATRO SF, Japan) were performed. Overall sensitivity, negative predictive value (NPV) and specificity of the D-dimer test were 98%, 98% and 42%. The optimal cut-off point for the Auto LIA-FM test was <or=3 microg/ml with values of 88%, 88% and 59%, respectively. The IATRO SF test had an optimal cut-off point of <or=2 microg/ml with values of 92%, 81 and 22%, respectively. The NPV of a non-high clinical score and a normal D-dimer (n=97) was 100%. In patients with a high clinical score (n=160), the NPV of the D-dimer was 88%. In these patients, a single US combined with a normal D-dimer or FM test had an equal NPV as serial US (100 versus 98%, respectively) and lead to a reduction in the need for US by 36-53%, respectively. In patients with abnormal D-dimer concentrations (n=343), a normal US combined with a normal Auto LIA-FM test had a NPV of 97%, which was also true for serial US. This could lead to a reduction in the need for US by 45%. The present studied FMs are inferior to the Tina-Quant D-dimer test when used as primary screening tool to exclude DVT. Adding these FMs to patients with a normal Tina-Quant D-dimer has no benefit. In patients with a high pretest clinical probability score, a single US in combination with a normal D-dimer or FM test might be as safe as serial US. In patients with abnormal D-dimer concentrations and a normal US, a normal FM test might be able to replace the second US.
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ABSTRACT: The exclusion of deep venous thrombosis (DVT) in the elderly is hampered by low specificity in clinical decision of D-dimer assays in older patients. To reduce false-positive results, we evaluated specific fibrin(ogen) degradation product assays for their contribution in the diagnosis of DVT. In a post-hoc study with outpatients suspected for DVT, we evaluated the elastase-specific fibrinogen (fibrinogen elastase degradation product, FgEDP) and D-E-specific fibrin (fibrin degradation product, FbDP) degradation product assays in relation to DVT. Results were combined with five D-dimer assays as ratio, with a specific focus on age-dependency. In 437 patients (DVT prevalence 39%), FgEDP correlated with D-dimer in DVT-negative patients (P < 0.001), but not in DVT-positive patients (P > 0.55). FbDP results correlated with D-dimer in both groups (P < 0.001). The values of the area under the curve of the receiver operating characteristic curve for both assays were lower than D-dimer. Using the ratios, only in the fourth age quartile D-dimer/FgEDP ratios had diagnostic value with lower number needed to test (1.8-12.7) as compared to D-dimer less than 500 μg/l alone (5.4-102). The D-dimer/FbDP ratios in DVT-negative elderly patients increased to a plateau by increasing D-dimer. In DVT-positive patients, these ratios were near constant for increasing values of D-dimer. In elderly patients, the D-dimer/FgEDP ratios may improve the number of patients in whom DVT could be excluded. The D-dimer/FbDP ratios showed differences in composition of fibrin degradation products between DVT-negative and DVT-positive patients and between young and old DVT-negative patients.Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 11/2012; · 1.25 Impact Factor
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ABSTRACT: Many studies have investigated the clinical accuracy of the D-dimer test in combination with pretest probability score for deep venous thrombosis (DVT) exclusion. However, few have evaluated its potential when combined with additional markers such as fibrin monomer. The aim of this study was to test the incremental usefulness of fibrin monomer for DVT screening in a bi-marker approach. This was achieved by adding the fibrin monomer to logistic models that included different D-dimer tests. Plasma concentrations of D-dimer and fibrin monomer were measured in 96 outpatients suspected of having DVT and in 76 patients selected from the total patient group according to pretest probability score (termed the DVT-unlikely group). We constructed receiver operating characteristic curves for three different D-dimer assays. Predictive probabilities from different logistic regression models and pair-wise comparisons of the areas under the receiver operating characteristic curve (AUCs) were calculated without and with fibrin monomer included in the models. For all three D-dimer assays, the AUCs were higher in the DVT-unlikely group compared with AUCs in the total patient group [but the differences were without statistical significance (P > 0.05)]. The calculated fibrin monomer AUCs (0.724 in the total patient group and 0.683 in the DVT-unlikely group) were lower than the D-dimer tests' AUCs. The AUCs obtained from logistic regression models that included the three D-dimer tests in the total patient group and the DVT-unlikely group were significantly increased when fibrin monomer was included in the model to such an extent that the AUCs for one of them indicated outstanding discriminative abilities. Simultaneous D-dimer and fibrin monomer determination provides a more valuable approximation for DVT exclusion compared with just D-dimer analysis. Bearing in mind that the fibrin monomer assay is now both more practical and more suited for routine clinical use, fibrin monomer determination could be a more commonly used parameter together with D-dimer and pretest probability score for DVT diagnosis in the future.Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 09/2009; 20(7):546-51. · 1.25 Impact Factor
Article: Analytisch: Hematologie