Delayed release of an abnormal fibrinopeptide A from fibrinogen Manchester: effect of the Aα 16 Arg → His substitution upon fibrin monomer polymerization and the immunological crossreactivity of the peptide

1983 ◽  
Vol 53 (4) ◽  
pp. 587-597 ◽  
Author(s):  
D. A. Lane ◽  
C. Southan ◽  
H. Ireland ◽  
E. Thompson ◽  
M. Kehl ◽  
...  
Keyword(s):  
Fibrinopeptide A ◽  
Delayed Release ◽  
Fibrin Monomer ◽  
Immunological Crossreactivity

scholarly journals Hemostatic evaluation in patients with prosthetic heart valves with special reference to fibrinopeptide A and soluble fibrin monomer complex.

1986 ◽  
Vol 17 (3) ◽  
pp. 242-247
Author(s):  
Masaharu HANANO ◽  
Hoyu TAKAHASHI ◽  
Tohru IZUMI ◽  
Tomio TAKESHIGE ◽  
Sinichiro TAKIZAWA ◽  
...  
Keyword(s):  
Special Reference ◽  
Heart Valves ◽  
Prosthetic Heart Valves ◽  
Fibrinopeptide A ◽  
Soluble Fibrin ◽  
Fibrin Monomer

Fibrinogen Zurich I: Impaired Release of Fibrinopeptide A

1979 ◽  
Vol 41 (04) ◽  
pp. 709-713 ◽  
Author(s):  
V Hofmann ◽  
W P Gati ◽  
P W Straub
Keyword(s):  
Normal Population ◽  
Fibrinopeptide A ◽  
Fibrin Monomer

SummaryFibrinogen Zurich I is characterized by an abnormal fibrin monomer polymerization. It consists of two fractions of molecules, one with a normal aggregation and one not aggregating at all and interfering with the aggregation of the normal population. Using a radioimmunoassay for fibrinopeptide A, only approximately half of the expected fibrinopeptide A could be recovered after thrombin or Defibrase proteolysis. The defective fibrinopeptide A release could be confirmed by measurement of the N-terminal Gly/Tyr ratio. It is likely that the abnormal fibrin monomer aggregation of the abnormal fraction of fibrinogen Zurich I is due to the defective fibrinopeptide A release of this fraction.

Dysfibrinogenaemia Characterized by Abnormal Fibrin Monomer Polymerization and Normal Fibrinopeptide A Release

1980 ◽  
Vol 44 (3) ◽  
pp. 483-494 ◽  
Author(s):  
D. A. Lane ◽  
B. Cuddigan ◽  
M. VanRoss ◽  
V. V. Kakkar
Keyword(s):  
Fibrinopeptide A ◽  
Fibrin Monomer

Polymerisation Defect of Fibrinogen London

1979 ◽  
Author(s):  
D.A. Lane ◽  
M. VanRoss ◽  
B. Cuddigan ◽  
V.V. Kakkar
Keyword(s):  
Ionic Strength ◽  
Gel Electrophoresis ◽  
Fibrinopeptide A ◽  
Protamine Sulphate ◽  
Terminal Domain ◽  
Coagulation Defect ◽  
Fibrin Monomer ◽  
Ca Ions ◽  
Polypeptide Chains ◽  
Fibrin Monomers

In the present study further work has been carried out on fibrinogen that has been isolated from a patient with a coagulation defect tentatively designated fibrinogen London. The dysfibrinogenemia was characterised by normal polypeptide chains on SDS gel electrophoresis, normal release of fibrinopeptide A and a delayed polymerisation of fibrin monomers. The polymerisation defect was pH and ionic strength dependent and partially corrected by protamine sulphate and Ca++ ions. Studies on the NH2 and COOH terminal polymerisation domains were carried out using insolubilised fibrin monomers prepared from patient and normal fibrinogen (Kudryk et al, Thromb. Res, 9,25. 1976). High MW fragment D, prepared by plasmin digestion of normal fibrinogen, bound to both normal and patient fibrin monomer and was eluted with 8M urea indicating no gross malfunction of the NH2 terminal polymerisation domain. Also purified fibrinogens from normal and patient plasma a bound to normal fibrin monomer sepharose, suggesting that the COOH terminal domain is capable of binding to the NH2 terminal domain of normal fibrin. These results suggest that the polymerisation defect of fibrinogen London is different in character to that of fibrinogen Detroit, where the NH2 terminal domain does not bind to the normal COOH terminal domain.

scholarly journals Kinetic characterization of a saturable pathway for rapid clearance of circulating fibrin monomer

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 680-688
Author(s):  
BN Dardik ◽  
JR Shainoff
Keyword(s):  
Plasma Concentrations ◽  
Kinetic Mechanism ◽  
Soluble Form ◽  
Order Kinetic ◽  
Fibrinopeptide A ◽  
Extravascular Space ◽  
Fibrin Monomer ◽  
Aggregation Site ◽  
Rapid Clearance ◽  
Alpha Beta

The mechanism of clearance of circulating fibrin monomer was investigated in rabbits through (1) study of decay in plasma concentrations of 125I-labeled monomers with variant fibrinopeptide content and (2) concurrent analysis of decay of the monomers relative to coinjected 131I-fibrinogen. Under the conditions employed, essentially all of the fibrin became distributed in a soluble form in plasma and decayed independently of the coinjected fibrinogen. Among the species of fibrin studied, monomer lacking fibrinopeptide A alone (alpha-fibrin) underwent very rapid clearance by a saturable mechanism that was not evident in relatively sluggish clearance of monomer lacking either fibrinopeptide B alone (beta-fibrin) or both fibrinopeptides A and B (alpha beta-fibrin). Decay of alpha-fibrin conformed with a kinetic mechanism involving first-order permeation of the fibrin into extravascular space at a rate equivalent to that of permeation of fibrinogen; unlike fibrinogen, however, the alpha-fibrin underwent immediate absorption in parallel with permeation (t1/2 = 2.6 hours) at doses below an apparent saturating level of 3 mg/kg. At doses near the absorptive limit, the uptake accompanying permeation diminished as in a second-order kinetic mechanism, and at very high doses the plasma decay of the alpha-fibrin approached that of fibrinogen. The beta- and alpha beta-fibrins also permeated extravascular space in parallel with fibrinogen, but absorption proceeded sluggishly (t1/2 = 11 and 16 hours, respectively) at low doses and did not change with increasing dose. The uniquely rapid and saturable clearance of alpha-fibrin is suggested to involve uptake through the fibrin aggregation site that is blocked by fibrinopeptide A in fibrinogen and beta-fibrin and by tight binding to fibrinogen in soluble complexes formed by alpha beta-fibrin. A corollary of this hypothesis is that rapid uptake depends on dissociability of fibrin complexes for access to the aggregation site, a mechanism that is just the converse of uptake through aggregation.

scholarly journals Kinetic characterization of a saturable pathway for rapid clearance of circulating fibrin monomer

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 680-688 ◽  
Author(s):  
BN Dardik ◽  
JR Shainoff
Keyword(s):  
Plasma Concentrations ◽  
Kinetic Mechanism ◽  
Soluble Form ◽  
Order Kinetic ◽  
Fibrinopeptide A ◽  
Extravascular Space ◽  
Fibrin Monomer ◽  
Aggregation Site ◽  
Rapid Clearance ◽  
Alpha Beta

Abstract The mechanism of clearance of circulating fibrin monomer was investigated in rabbits through (1) study of decay in plasma concentrations of 125I-labeled monomers with variant fibrinopeptide content and (2) concurrent analysis of decay of the monomers relative to coinjected 131I-fibrinogen. Under the conditions employed, essentially all of the fibrin became distributed in a soluble form in plasma and decayed independently of the coinjected fibrinogen. Among the species of fibrin studied, monomer lacking fibrinopeptide A alone (alpha-fibrin) underwent very rapid clearance by a saturable mechanism that was not evident in relatively sluggish clearance of monomer lacking either fibrinopeptide B alone (beta-fibrin) or both fibrinopeptides A and B (alpha beta-fibrin). Decay of alpha-fibrin conformed with a kinetic mechanism involving first-order permeation of the fibrin into extravascular space at a rate equivalent to that of permeation of fibrinogen; unlike fibrinogen, however, the alpha-fibrin underwent immediate absorption in parallel with permeation (t1/2 = 2.6 hours) at doses below an apparent saturating level of 3 mg/kg. At doses near the absorptive limit, the uptake accompanying permeation diminished as in a second-order kinetic mechanism, and at very high doses the plasma decay of the alpha-fibrin approached that of fibrinogen. The beta- and alpha beta-fibrins also permeated extravascular space in parallel with fibrinogen, but absorption proceeded sluggishly (t1/2 = 11 and 16 hours, respectively) at low doses and did not change with increasing dose. The uniquely rapid and saturable clearance of alpha-fibrin is suggested to involve uptake through the fibrin aggregation site that is blocked by fibrinopeptide A in fibrinogen and beta-fibrin and by tight binding to fibrinogen in soluble complexes formed by alpha beta-fibrin. A corollary of this hypothesis is that rapid uptake depends on dissociability of fibrin complexes for access to the aggregation site, a mechanism that is just the converse of uptake through aggregation.

In Vitro and in Vivo Induction of Cryofibrinogen and “Paracoagulation” by Reptilase

1972 ◽  
Vol 27 (02) ◽  
pp. 337-348 ◽  
Author(s):  
A.J Harder ◽  
P.W Straub
Keyword(s):  
Snake Venom ◽  
Sedimentation Rate ◽  
Fibrinopeptide A ◽  
Intravascular Coagulation ◽  
Fibrin Monomer ◽  
Small Doses ◽  
In Vivo Induction

SummarySmall doses of Reptilase, a snake venom enzyme which exclusively liberates fibrinopeptide A from fibrinogen, leads to formation of cryofibrinogen as well as ethanol- and protamine-precipitability of plasma both in vitro and in vivo. Precipitates obtained in vitro were shown to contain both fibrinogen and fibrin monomer. At 20° C Reptilase-treated fibrinogen solutions contained complexes with a sedimentation rate of 11-11.6 s20W, similar to those observed after thrombin. The artificial production of cryofibrinogenemia in volunteers is discussed in relation to spontaneously occurring cryofibrinogenemias in patients with intravascular coagulation.

Fibrin Detected in Plasma of Patients with Disseminated intravascuiar Coagulation by Fibrin-specific Antibodies Consists Primarily of High Molecular Weight Factor XIIIa-crosslinked and Plasmin-modified Complexes Partially Containing Fibrinopeptide A

1997 ◽  
Vol 78 (03) ◽  
pp. 1069-1078 ◽  
Author(s):  
Susanne A Pfitzner ◽  
Carl-Erik Dempfle ◽  
Michio Matsuda ◽  
Dieter L Heene
Keyword(s):  
Molecular Weight ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Factor Xiiia ◽  
Fibrinopeptide A ◽  
Weight Factor ◽  
Fibrin Monomer ◽  
N Terminus ◽  
Α Chain ◽  
D Dimer

SummaryPooled plasma from 40 patients with severe disseminated intravascuiar coagulation (DIC) secondary to septic conditions was subjected to gel permeation chromatography on Sephacryl S-500 HR after sample pretreatment with KSCN for dissociation of non-covalent fibrin complexes. Fibrin antigen in eluates was detected by an array of ELISA tests, using two monoclonal antibodies against fibrin degradation product D-dimer, a monoclonal antibody against an epitope generated by plasmin cleavage of the D-domain, and an antibody against the neo-N- terminus of the α-chain of fibrin exposed by cleavage of fibrinopeptide A. Tag antibodies were a polyclonal antibody against the fibrinogen/ fibrin D-domain, a POD-conjugated version of the monoclonal antibody against fibrin α-chain neo-N-terminus, and a polyclonal antibody against fibrinopeptide A. Most fibrin-related material present in the pooled DIC plasma was of higher molecular mass than fibrinogen. Fibrin polymers were reactive with antibodies against D-dimer, plasmin cleaved D-domain, and fibrin α-chain neo-N-terminus. Part of the polymers reacted with antibodies against fibrinopeptide A, indicating presence of fibrinogen or desA-fibrin monomer within the covalently linked complex. In conclusion, the primary analytes detected by monoclonal antibodies for D-dimer, plasmin-specific epitopes of fibrin degradation products, as well as sites exposed by fibrinopeptide cleavage in plasma from patients with disseminated intravascuiar coagulation are high molecular weight factor XIIIa-crosslinked fibrin complexes, containing plasmin-cleaved D-domains, intact fibrin monomer units, and fibrinogen or desA-fibrin monomer.

Course of indicators of thrombin activity in the early phase of acute myocardial infarction: effect of fibrinolytic therapy and acute percutaneous coronary angioplasty

2003 ◽  
Vol 90 (07) ◽  
pp. 147-154 ◽  
Author(s):  
Jens Kaden ◽  
Karl Haase ◽  
Martin Borggrefe ◽  
Carl-Erik Dempfle
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Fibrinolytic Therapy ◽  
Fibrinopeptide A ◽  
Platelet Surface ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
Thrombin Activity ◽  
D Dimer

SummaryWe evaluated assay systems for detection of in vivo thrombin activity in patients with acute myocardial infarction. The study included 31 consecutive patients with acute myocardial infarction treated either with fibrinolytic therapy (FLT), or acute PTCA. Blood samples were drawn at admission, after 30 min, 1 h, 3 h, 6 h, 12 h, 24, and 48 h. Assays related to the enzymatic action of thrombin included fibrinopeptide A ELISA, a novel latex-enhanced photometric immunoassay for soluble fibrin complexes, fibrin monomer antigen, D-dimer antigen, and soluble platelet glycoprotein V, which is released from the platelet surface by thrombin cleavage.The soluble fibrin assay displayed a high degree of correlation with fibrinopeptide A, and no correlation with D-dimer antigen, indicating that this parameter allows monitoring of in vivo thrombin activity in patients with acute myocardial infarction. Fibrin monomer antigen, and D-dimer antigen, were influenced by FLT, indicating cross-reactivity with proteolytic fragments of fibrin. No significant changes in soluble glycoprotein V were observed.The results show that the novel soluble fibrin assay appears to be a promising method for measurement of in vivo fibrin formation in patients with acute myocardial infarction, irrespective of the primary treatment decision for FLT or acute PTCA.

Fibrinogen Matsumoto V: a Variant with Aα19 Arg → Gly (AGG → GGG)

2001 ◽  
Vol 85 (01) ◽  
pp. 108-113 ◽  
Author(s):  
Hitoshi Tanaka ◽  
Fumiko Terasawa ◽  
Toshiro Ito ◽  
Shin-ichi Tokunaga ◽  
Fumihiro Ishida ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Normal Control ◽  
Amino Acid Residue ◽  
Systemic Lupus Erythematous ◽  
Fibrinopeptide A ◽  
Systemic Lupus ◽  
Fibrin Polymerization ◽  
Fibrin Monomer ◽  
A Site

SummaryFibrinogen Matsumoto V (M-V) is a dysfibrinogen identified in a 52-year-old woman with systemic lupus erythematous. The triplet AGG encoding the amino acid residue Aα19 was replaced by GGG, resulting in the substitution of Arg→Gly. Residue Aα19 has been shown to be one of the most important amino acids in the so-called ‘A’ site or α-chain knob. The thrombin-catalyzed release of fibrinopeptide A from M-V fibrinogen was only slightly delayed yet release of fibrinopeptide B was significantly delayed. Both thrombin-catalyzed fibrin polymerization and fibrin monomer polymerization were markedly impaired compared to normal fibrinogen. In addition, reptilase-catalyzed fibrin polymerization of M-V was much more impaired than thrombin-catalyzed fibrin polymerization. These results indicate ‘B’ and/or ‘b’ site of M-V fibrinogen play a more important role in thrombin- catalyzed fibrin polymerization than that of normal control fibrinogen.

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