Binding of a new monoclonal antibody against N-terminal heptapeptide of fibrin α-chain to fibrin polymerization site ‘A’

Dempfle, Carl-Erik; Dollman, M.; Lill, Helmut; Puzzovio, D; Dessauer, Andreas; Heene, D. L.

doi:10.1097/00001721-199302000-00013

Cited by 25 publications

(22 citation statements)

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“…Early test systems for soluble fibrin included the ethanol gelation test (12), protamine paracoagulation assays (13), and the erythrocyte agglutination assay (14,15). Later assays were based on the cofactor role of soluble fibrin in t-PA-induced plasminogen activation (16), and on specific epitopes generated by release of fibrinopeptides A from fibrinogen (17)(18)(19), and fibrin polymerization (8,(20)(21)(22)(23)(24). To date, no published studies have demonstrated an advantage for the determination of soluble fibrin or fibrin monomer over D-dimer antigen in the diagnosis or prognosis of defined clinical conditions.…”

Section: Discussionmentioning

confidence: 99%

Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score

Dempfle¹,

Wurst²,

Smolinski³

et al. 2004

Thromb Haemost

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The overt DIC score of the DIC subcommittee of the ISTH includes a fibrin-related marker (FRM) as indicator of intravascular fibrin formation. The type of marker to be used has not been specified, but D-dimer antigen, or fibrin degradation products are used by most investigators. Soluble fibrin complexes have been suggested as more specific indicators of acute intravascular fibrin formation. The aim of the present study was to compare the predictive value of the overt DIC score concerning clinical outcome in a surgical intensive care cohort, using either D-dimer antigen, or soluble fibrin antigen as FRM. The cutoff values for 2 and 3 score points for the FRM were assigned on the basis of the 25% and 75% quartiles of 1870 plasma samples obtained from 359 ICU patients during a period of 6 months. For 331 patients with complete diagnostic workup and day 1 blood samples, the Iatro SF as FRM component of the overt DIC score displayed the highest prognostic power concerning clinical outcome. The 28-day mortality of patients with overt DIC at day 1, using Iatro SF as FRM assay was 50.0%, whereas 28-day mortality of patients without overt DIC was 14.0% (p <0.0001). Using MDA D-dimer, and TINAquant D-dimer, 28-day mortality was between 35.5% and 39.3% in patients with overt DIC, and 15.5% to 15.6% in patients without overt DIC. Selection of the FRM as component of the DIC score has a small, but relevant impact on the prognostic performance of the overt DIC score. The present data on the distribution of values may provide a basis for the selection of appropriate cutoff points for assigning 2, and 3 points in the score.

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Section: Discussionmentioning

confidence: 99%

Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score

Dempfle¹,

Wurst²,

Smolinski³

et al. 2004

Thromb Haemost

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“…Anti-FPA mAb binds both the free peptide and the intact segment at the N terminus of the A␣-chain of fibrinogen (A␣1-16). Anti-fibrin ␣17-23 mAb was affinity-purified as described (30) and binds to fibrin lacking FPA, but not to fibrinogen with FPA intact. The binding of anti-fibrin ␣17-23 mAb to fibrin occurs only after denaturation of the fibrin (30).…”

Section: Methodsmentioning

confidence: 99%

“…To address this question, we carried out electrophoretic analyses using GPR analogs of the fibrin aggregation site as aggregation inhibitors to stage gel shifts that distinguish the self-aggregating from the non-aggregating derivatives in thrombin/fibrinogen reaction mixtures. We subsequently immunoprobed the gels with anti-FPA mAb (anti-fibrinogen A␣1-16) (29) and anti-fibrin ␣17-23 mAb (30) to distinguish the components retaining FPA from those lacking it, respectively. The results demonstrate that an intermediary product lacking one FPA is, indeed, produced prior to detectable ␣-fibrin monomer, but this intermediate, which we call "␣-profibrin," has such weak aggregation characteristics that it is difficult to distinguish it from fibrinogen, except for differences in strength of complexing with fibrin monomer.…”

mentioning

confidence: 99%

Isolation and Characterization of the Fibrin Intermediate Arising from Cleavage of One Fibrinopeptide A from Fibrinogen

Shainoff

Smejkal

DiBello

et al. 1996

Journal of Biological Chemistry

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The thrombin-catalyzed cleavage of N-terminal fibrinopeptide A (FPA) from the two Aalpha-chains of fibrinogen exposes aggregation sites with the critical sequence GPR located just behind FPA. It is well known that exposure of both GPR sites transforms fibrinogen into self-aggregating, fully coagulable alpha-fibrin monomers, but the fibrin precursor with one site exposed and one FPA intact has eluded description. The formation of this "alpha-profibrin" in the course of thrombin reactions and its distribution among both the aggregating and non-aggregating components of the reactions are characterized here by immunoprobing electrophoretic and gel chromatographic separations using monoclonal antibodies specific for FPA and for exposed GPR sites. These analyses show alpha-profibrin to be a non-aggregating derivative indistinguishable from fibrinogen in solutions that are rich in fibrinogen relative to dissolved fibrin. But alpha-profibrin forms soluble complexes with alpha-fibrin monomer under conditions in which it and fibrin predominate over fibrinogen. It was isolated as a complex with fibrin by gel chromatography of cryoprecipitates and then separated from the fibrin either by electrophoretic gel shifts induced with a peptide analog of the GPR aggregation site or by chromatographic gel shifts induced with monoclonal anti-FPA antibody. The weak aggregation of alpha-profibrin with itself and with fibrinogen conforms with prior indications that coupled interactions through the paired GPR sites on fibrin monomers are pivotal to their aggregation. It is suggested that alpha-profibrin may be a hypercoagulable fibrin precursor because it is converted to alpha-fibrin monomer faster than fibrinogen converts to monomer.

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“…The kit is performed in streptavidin-coated polystyrene assay tubes, using monoclonal antibody 2B5 as biotinconjugated capture antibody and perioxidase-labelled tagging antibody, specific for the N-terminal heptapeptide of the fibrin u-chain [19,20]. (MRR: 0.0-6.Opg/ ml).…”

Section: Assaysmentioning

confidence: 99%

Postoperative Activation of the Haemostatic System - Influence of Prolonged Thromboprophylaxis in Patients Undergoing Total Hip Arthroplasty

Andersen

1997

Pathophysiol Haemos Thromb

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Tissue injury during hip surgery results in the activation of the haemostatic system. The aim of this study was to detect markers of haemostatic activity, i.e. prothrombin fragment 1 and 2 (Fl+2), thrombin-antithrombin (TAT) complexes, fibrin degradation products (FbDP), and soluble fibrin monomers (SF), preoperatively, and on days 1, 7 and 35 in plasma of patients undergoing total hip arthroplasty. The study was part of a mul-ticentre study in which the patients were randomized to receive a subcutanous injection of low molecular weight heparin (LMWH, dalteparin, Fragmin®) once daily for 5 weeks or placebo following a 1-week LMWH treatment (once daily). Bilateral phlebography was performed between days 33 and 35 or before if patients had clinical symptoms of deep vein thrombosis. A lung scan was performed in patients with clinical symptoms of pulmonary embolism. Levels of the markers were significantly increased on day 35 in the patients receiving LMWH for 7 days compared to patients receiving LMWH for 35 days. In patients receiving LMWH for 5 weeks, levels of FbDP and SF were significantly higher during the entire study period, but TAT and Fl+2 were normalized on day 35. The markers were increased two to five times on the 1 st postoperative day in patients with diagnosed venous thromboembo-lism.

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Binding of a new monoclonal antibody against N-terminal heptapeptide of fibrin α-chain to fibrin polymerization site ‘A’

Cited by 25 publications

References 0 publications

Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score

Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score

Isolation and Characterization of the Fibrin Intermediate Arising from Cleavage of One Fibrinopeptide A from Fibrinogen

Postoperative Activation of the Haemostatic System - Influence of Prolonged Thromboprophylaxis in Patients Undergoing Total Hip Arthroplasty

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