Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the course of fibrin formation, the D-domains of adjacent fibrin molecules within the fibrin polymer are covalently linked by factor XIIIa, leading to the formation of a D-domain dimer. Proteolysis of this cross-linked fibrin generates fibrin fragments D-dimer and E as terminal products. Fragment D-dimer therefore is an indicator for the proteolysis of cross-linked fibrin, whereas the monomeric fragment D can stem from fibrinogen and non-cross-linked fibrin. Various monoclonal antibodies have been prepared that distinguish between fragments D-dimer and D and allow the detection of fibrin derivatives in the presence of fibrinogen. These anti-D-dimer-antibodies have been shown to react with fragment D-dimer, but also detect dimeric D-domains within larger fibrin compounds, including cross-linked fibrin complexes generated in an early phase of coagulation activation. Assay systems for D-dimer antigen therefore may uncover intravascular clot formation early, by detection of fibrin complexes, and after completion of clot formation, by the detection of proteolytic fragments released from the particulate clot. Various trials have shown that low concentrations of D-dimer antigen in the blood exclude recent venous thrombosis or pulmonary embolism. Elevated levels may be caused by venous thrombotic disease, but also by a variety of other conditions, leading to intra- or extravascular fibrin formation. Assay systems include manual immunoagglutination assays, immunofiltration assays, microtiter plate enzyme-linked immunosorbent assay (ELISA) systems, automated ELISA systems, and latex-enhanced photometric immunoassays. According to clinical studies, D-dimer assays may be the "first line" of technical screening in symptomatic outpatients with suspected venous thrombosis or pulmonary embolism, but further prospective management trials, and improved standardization of assay systems, are needed for the validation of this approach.
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PMID:Use of D-dimer assays in the diagnosis of venous thrombosis. 1114 Aug

D-dimer is an indicator for in vivo fibrin formation, reflecting the formation of fibrin crosslinked by factor XIIIa. D-dimer assays are frequently used in emergency situations, such as diagnosis of venous thrombosis and pulmonary embolism, or disseminated intravascular coagulation. In these conditions, short sample turnaround times are essential. The PATHFAST D-dimer assay allows rapid quantitative measurement of D-dimer in plasma and whole blood. The study shows an excellent correlation between whole blood and plasma measurement of D-dimer both in the high range, as well as in the normal range. Intra-assay and inter-assay coefficients of variation (CV) were below 10%. The upper limit of normal (ULN = mean value measured in 100 samples from healthy blood donors + 2 x S.D.) was approximately 1 microg/ml FEU, using the assay-specific calibration. The maximal value measured in 20 replicates of calibrator 1 containing no D-dimer antigen was 0.00052 microg/ml FEU, and this 10-fold lower than the declared detection limit of 0.005 microg/ml FEU. In conclusion, the PATHFAST D-dimer assay is the first automated fully quantitative D-dimer assay, which can use plasma and whole blood as sample materials in parallel.
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PMID:Performance evaluation of a new rapid quantitative assay system for measurement of D-dimer in plasma and whole blood: PATHFAST D-dimer. 1717 10

D-dimer is an important marker of different coagulation diseases, such as venous thromboembolism (including deep vein thrombosis and pulmonary embolism) and disseminated intravascular coagulation. Though it is frequently used in many clinical diagnostic situations, the D-dimer assays currently lack standardization due to its inherent heterogeneity which makes the antibody-based methods have different quantitative results and cutoffs to define an abnormal value. In this study, we report the first antibody-free D-dimer quantification method. In the method, a cross-linked peptide of fibrin D domain carboxyl terminal cross-linked by the factor XIIIa was used to represent the D-dimer. By using a filter-aided sample preparation and a nickel immobilized metal affinity chromatography enrichment strategy, the complexity of the plasma sample was significantly reduced, and the cross-linked peptide was enriched effectively for analysis with parallel reaction monitoring in mass spectrometry. The linear range of this method was 3.125-400 nmol/L which spans over two magnitudes. Recovery and reproducibility of the method were found to be good. To further demonstrate the performance of our method, D-dimer concentrations of 25 human plasma samples were analyzed, and the results had a good correlation between with the commercial D-dimer assay kit used in hospitals. This method was completely antibody-free and has the potential to promote the standardization of D-dimer analysis.
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PMID:A Mass-Spectrometry-Based Antibody-Free Approach Enables the Quantification of D-Dimer in Plasma. 3251 45