New Combinational Assay Using Soluble Fibrin and D-Dimer Determinations: A Promising Strategy for Identifying Patients with Suspected Venous Thromboembolism

AIM: To establish a new and reliable assay for quantification of the soluble fibrin (SF) in combination with that of D-dimer for early diagnosis of venous thromboembolism. METHODS AND SAMPLES: The SF assay is based on D-dimer generated after incubation of plasma with tissue-type plasminogen activator (t-PA). SF and standard D-dimer assays, run in blind, were used to test 119 untreated outpatients with clinically suspected deep-vein thrombosis (DVT, 49 patients) or pulmonary embolism (PE, 70 patients) consulting at the emergency unit of the hospital. Thromboses were confirmed by current imaging methods such as ultrasonography, scintigraphy, computed tomographic pulmonary angiography (CTPA) and ventilation/perfusion scan. RESULTS: SF assay was validated in 270 healthy volunteers [51.8% males; mean age years ± SD: 41±13; age range 19 to 65]. Among these normal plasmas, SF levels were ≤200 ng/mL in 97.8% of them, and 200–250 ng/mL in the remainder [26–46 years old; 50% males]. ROC curves were used to determine the SF cut-off value for plasma SF positivity, which was found to be 300 ng/mL. In patients with suspected venous thromboembolism, SF sensitivities for DVT and PE (92% and 94%, respectively) were comparable to those of D-dimer (96% and 94%), whereas SF specificities (86% and 95%) were higher than those of D-dimer (50% and 54%). Positive-predictive values for SF (89% and 94%) were again higher than those of D-dimer (70% and 65%) in DVT and PE. The amount of circulating SF normalized rapidly after anticoagulant therapy. CONCLUSION: Results from this small group of patients suggest that the evaluation of plasma SF, in combination with that of D-dimer, represents a potentially useful tool for the early diagnosis of venous thromboembolism, provided that the patients have not been treated previously by anticoagulants.