Subunit and macromolecular structure of circulating fibrin from obstetric patients with intravascular coagulation

Graeff, H.; Hafter, R.; Bachmann, L.

doi:10.1016/0049-3848(79)90079-3

Cited by 37 publications

(29 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…35 The binding of thrombin36,37 and factor X11I38 to fibrin may explain the increase in thrombin-catalyzed factor XIIIa by fibrin polymers in plasma.10 Prior studies provided indirect evidence for circulating crosslinked fibrin polymers by identifying y chain dimers in extracts of plasma obtained from patients with thrombotic disease. [15][16][17][18][19]39 Using an electrophoretic technique, we have shown directly a low concentration of crosslinked fibrin dimer in normal plasma and a significant elevation in patients with acute myocardial infarction. 7 Tissue plasminogen activator has a high affinity for fibrin29,30 and preferentially activates fibrinbound plasminogen,4041 which are properties that localize physiologic fibrinolysis and that also form the theoretical basis for the relative fibrin selectivity of t-PA as a therapeutic agent.…”

Section: Discussionmentioning

confidence: 99%

Increased immunoreactivity of plasma after fibrinolytic activation in an anti-DD ELISA system. Role of soluble crosslinked fibrin polymers.

et al. 1989

View full text Add to dashboard Cite

After addition of a low concentration of thrombin to normal plasma, a progressive and significant increase in crosslinked fibrin polymers was found by sodium dodecyl sulfate agarose gel electrophoresis, reaching 27% of total fibrinogen and fibrin before gel formation. As measured by enzyme-linked immunosorbent assay with a monoclonal antibody specific for an epitope near the yy crosslink site, increased immunoreactivity of plasma did not occur after adding thrombin despite formation of crosslinked fibrin polymers, which indicates that the antibody does not recognize the epitope in the polymers. Addition of tissue-type plasminogen activator (t-PA) to plasma resulted in a more rapid degradation of fibrin polymers than of fibrinogen, indicating that the fibrin specificity of t-PA is retained with soluble fibrin. Coincident with degradation of plasma crosslinked fibrin polymers, plasma DD immunoreactivity increased 70-fold from 50.3±4.5 (mean±SD) to 3,560±1,235 ng/ml. The presence of increased crosslinked fibrin polymers produced by adding thrombin to plasma significantly increased maximum immunoreactivity after t-PA-induced degradation to 18,500±11,780 ng/ ml. The increase in DD immunoreactivity was dependent on t-PA concentration; no elevation occurred below 0.01 ug/ml, and maximal increases occurred above 100 ,ug/ml. Analysis of gel electrophoretic patterns of thrombin and t-PA-treated plasma samples suggests that the DD reactivity of t-PA-treated plasma is mainly due to degradation of soluble crosslinked fibrin polymers. Our findings indicate that plasmic degradation of soluble fibrin polymers in plasma may be an important source of fragment DD during thrombolytic therapy. (Circulation 1989;79: 666-673) U nder physiologic conditions, fibrin formation is localized either intravascularly in the formation of hemostatic plugs or extravascularly in inflammatory foci. However, low concentrations of soluble fibrin circulate, and increased concentrations have been identified in patients with thrombotic disease,1-7 reflecting a systemic effect of thrombin activity that can also be measured by plasma fibrinopeptide levels.8,9 Solu-

show abstract

Section: Discussionmentioning

confidence: 99%

Increased immunoreactivity of plasma after fibrinolytic activation in an anti-DD ELISA system. Role of soluble crosslinked fibrin polymers.

et al. 1989

View full text Add to dashboard Cite

show abstract

“…Studying the time course, using the same in vitro method, members of the same group found that crosslinked fibrin was degraded rapidly, liberating 75% of the insoluble material within 2 h and dissolving 96% of it in 48 h. A method to detect circulating crosslinked derivatives of fibrin by a heat extraction-SDS gel electrophoretic technique was also developed and suggested that high molecular weight fibrinolysis products were circulating during DIC as also proposed previously by others [6]. The subunit structure of circulating fibrin and fibrin degradation products have also been later discussed by others, for example [5,23]. The calibration method presented is however suited for methods giving similar results for early and late fibrinolysis products.…”

Section: General Remarksmentioning

confidence: 88%

A proposed stoichiometrical calibration procedure to achieve transferability of D-dimer measurements and to characterize the performance of different methods

Edlund

Nilsson

2006

Clinical Biochemistry

View full text Add to dashboard Cite

“…It was presumed that D dimer would be the largest soluble fragment derived from crosslinked insoluble fibrin. However, subsequently soluble domainal aggregates of about 2 × 10 6 molecular weight have been generated from fibrin by plasmin under controlled conditions of lysis,35 and similar fragments have been found in blood during a variety of clinical states 36–39. These variously sized fragments of fibrin are held together by both the non‐covalent fibrin polymerization bonds and the g chain crosslinks that were present in the originating fibrin (see reviews in Refs.…”

Section: Fibrin Digestionmentioning

confidence: 99%

“…Large aggregates (X‐oligomers) held together by both γ chain crosslinks and fibrin polymerization sites can have molecular weights as large as or exceeding 2 × 10 6 daltons. The group of fragments indicated here as X‐oligomers37,38 has been characterized into various sized fractions,3 one of the major features of which is the number of X‐like structures in each of the subclassifications. Although Figure 3 shows only two types of XL‐FDP (one large and one small) the general formula for these fragments can be given as (Y/D‐X n ‐Y/D) 2 .…”

Section: Fibrin Digestionmentioning

confidence: 99%

Fibrin Degradation Products

Gaffney

2001

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

This review attempts to relate subunit structures of fibrin degradation products (FnDP) made in vitro with structures found in vivo. The domainally directed fragmentation in vitro of both fibrinogen and fibrin is emphasized, all fragments being various associations of the two core fibrin fragments D and E. The digestion of fibrinogen by plasmin in vivo is rare, and the crosslinking of fibrin in vivo takes place at a very early stage in the clotting/polymerization process. The notion that as fibrin forms in vivo it orchestrates its own destruction is developed. Plasmas from patients suffering from dessiminated intravascular coagulation demonstrate very large crosslinked FnDP fragments in their plasmas which seem to contain not alone fibrinopeptide A but also subunits with intact alpha chains. This is interpreted to mean that many of the large soluble fragments found in vivo, and heretofore known as FnDP, are in reality long fibrin polymers, random parts of whose structures have been converted to FnDP by lysis of the carboxy terminal regions of the alpha chains in the polymer. The ratio of intact fibrin to FnDP in these large soluble structures may be a useful clinical marker; however, such data can only be relied upon when blood samples are taken into an anticoagulant mix that contains a fibrinolytic inhibitor. Some of the biological effects of FnDP structures in vivo (fibrinogen synthesis, vasoactivity) are still quite ambiguous.

show abstract

Subunit and macromolecular structure of circulating fibrin from obstetric patients with intravascular coagulation

Cited by 37 publications

References 17 publications

Increased immunoreactivity of plasma after fibrinolytic activation in an anti-DD ELISA system. Role of soluble crosslinked fibrin polymers.

Increased immunoreactivity of plasma after fibrinolytic activation in an anti-DD ELISA system. Role of soluble crosslinked fibrin polymers.

A proposed stoichiometrical calibration procedure to achieve transferability of D-dimer measurements and to characterize the performance of different methods

Fibrin Degradation Products

Contact Info

Product

Resources

About