Analysis of fibrin formation and proteolysis during intravenous administration of ancrod

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2793-2802
Author(s):  
Carl-Erik Dempfle ◽  
Sotiria Argiriou ◽  
Klaus Kucher ◽  
H. Müller-Peltzer ◽  
Klaus Rübsamen ◽  
...  
Keyword(s):  
Degradation Products ◽  
Monomer Unit ◽  
Threshold Concentration ◽  
Tissue Type ◽  
Considerable Proportion ◽  
Fibrinogen Concentration ◽  
Stroke Treatment ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
High Concentrations

Ancrod is a purified fraction of venom from the Malayan pit viper, Calloselasma rhodostoma, currently under investigation for treatment of acute ischemic stroke. Treatment with ancrod leads to fibrinogen depletion. The present study investigated the mechanisms leading to the reduction of plasma fibrinogen concentration. Twelve healthy volunteers received an intravenous infusion of 0.17 U/kg body weight of ancrod for 6 hours. Blood samples were drawn and analyzed before and at various time points until 72 hours after start of infusion. Ancrod releases fibrinopeptide A from fibrinogen, leading to the formation of desAA-fibrin monomer. In addition, a considerable proportion of desA-profibrin is formed. Production of desA-profibrin is highest at low concentrations of ancrod, whereas desA-profibrin is rapidly converted to desAA-fibrin at higher concentrations of ancrod. Both desA-profibrin and desAA-fibrin monomers form fibrin complexes. A certain proportion of complexes carries exposed fibrin polymerization sites EA, indicating that the terminal component of the protofibril is a desAA-fibrin monomer unit. Soluble fibrin complexes potentiate tissue-type plasminogen activator-induced plasminogen activation. Significant amounts of plasmin are formed when soluble fibrin in plasma reaches a threshold concentration, leading to the proteolytic degradation of fibrinogen and fibrin. In the present setting, high concentrations of soluble fibrin are detected after 1 hour of ancrod infusion, whereas a rise in fibrinogen and fibrin degradation products, and plasmin-α2–plasmin inhibitor complex levels is first detected after 2 hours of ancrod infusion. Ancrod treatment also results in the appearance of cross-inked fibrin degradation productd-dimer in plasma.

Analysis of fibrin formation and proteolysis during intravenous administration of ancrod

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2793-2802 ◽  
Author(s):  
Carl-Erik Dempfle ◽  
Sotiria Argiriou ◽  
Klaus Kucher ◽  
H. Müller-Peltzer ◽  
Klaus Rübsamen ◽  
...  
Keyword(s):  
Degradation Products ◽  
Monomer Unit ◽  
Threshold Concentration ◽  
Tissue Type ◽  
Considerable Proportion ◽  
Fibrinogen Concentration ◽  
Stroke Treatment ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
High Concentrations

Abstract Ancrod is a purified fraction of venom from the Malayan pit viper, Calloselasma rhodostoma, currently under investigation for treatment of acute ischemic stroke. Treatment with ancrod leads to fibrinogen depletion. The present study investigated the mechanisms leading to the reduction of plasma fibrinogen concentration. Twelve healthy volunteers received an intravenous infusion of 0.17 U/kg body weight of ancrod for 6 hours. Blood samples were drawn and analyzed before and at various time points until 72 hours after start of infusion. Ancrod releases fibrinopeptide A from fibrinogen, leading to the formation of desAA-fibrin monomer. In addition, a considerable proportion of desA-profibrin is formed. Production of desA-profibrin is highest at low concentrations of ancrod, whereas desA-profibrin is rapidly converted to desAA-fibrin at higher concentrations of ancrod. Both desA-profibrin and desAA-fibrin monomers form fibrin complexes. A certain proportion of complexes carries exposed fibrin polymerization sites EA, indicating that the terminal component of the protofibril is a desAA-fibrin monomer unit. Soluble fibrin complexes potentiate tissue-type plasminogen activator-induced plasminogen activation. Significant amounts of plasmin are formed when soluble fibrin in plasma reaches a threshold concentration, leading to the proteolytic degradation of fibrinogen and fibrin. In the present setting, high concentrations of soluble fibrin are detected after 1 hour of ancrod infusion, whereas a rise in fibrinogen and fibrin degradation products, and plasmin-α2–plasmin inhibitor complex levels is first detected after 2 hours of ancrod infusion. Ancrod treatment also results in the appearance of cross-inked fibrin degradation productd-dimer in plasma.

Fibrinolytic system, fibrinogen degradation products and soluble fibrin monomer complexes of renal venous and aortal blood

1969 ◽  
Vol 25 (9) ◽  
pp. 996-997
Author(s):  
A. Nowak ◽  
S. Niewiarowski ◽  
Z. Czekala ◽  
K. Worowski ◽  
J. Dosiak ◽  
...  
Keyword(s):  
Degradation Products ◽  
Fibrinolytic System ◽  
Fibrinogen Degradation Products ◽  
Soluble Fibrin ◽  
Fibrin Monomer

scholarly journals General casual hypothermia as a threat of thrombosis in rats

2014 ◽  
Vol 95 (3) ◽  
pp. 385-388
Author(s):  
N A Lycheva ◽  
I I Shakhmatov
Keyword(s):  
Platelet Aggregation ◽  
Peripheral Blood ◽  
Adenosine Diphosphate ◽  
Cold Injury ◽  
Clotting Factor ◽  
Fibrinogen Concentration ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
Third Stage ◽  
Aggregation Activity

Aim. To study the hemostasis at the pre-reactive period of cold injury occurred at the third stage of the decompensated phase of general casual hypothermia. Methods. Experiments were performed on on 23 Wistar rats. General casual hypothermia was simulated by placing the animals in individual cages in a freezer with in-temperature of -25 °C. Animals were kept in the freezer until the rectal body temperature of +30 °С. Blood samples of 10 animals, kept at 22°C during the same exposure time, were used as a control. Hemostasis parameters, including platelets and coagulation panel, as well as blood serum anticoagulant and fibrinolytic activity, were assessed in peripheral blood. Induced platelet aggregation was measured by aggregometer, with 10 μg/ml adenosine diphosphate solution as the inductor. Results. General casual hypothermia was not associates with changes in the peripheral blood. At the same time, increased platelet count by 19% (р 0.05) and reduced platelet aggregation activity by 9 times (р 0.05) was observed. The coagulation panel at the pre-reactive period of cold injury was associated with Echitox coagulation time increase by 42% (р 0.05), together with fibrinogen concentration drop by 25% (р 0.05). Increased polymerization time of circulating soluble fibrin monomer complexes by 36% (р 0.05) was suggestive of reduced I clotting factor serum concentrations. In the same animals, the serum concentration of soluble fibrin monomer complexes was increased by 96% (р 0.05), suggesting the increased clotting activity. Conclusion. Decompensated phase of general casual hypothermia was associated with significant changes of on the hemostasis. The set of observed changes was suggestive of increased clotting activity as the response to the cold trauma and predisposition to clotting in experimental animals.

The Resistance of Soluble Derivatives of Fibrinogen and the Sensitivity of Its Insoluble Forms to Fibrinolytic Degradation in Blood

1974 ◽  
Vol 32 (02/03) ◽  
pp. 582-591 ◽  
Author(s):  
Victor Gurewich ◽  
Andrzej Nowak ◽  
Izabella Lipinska ◽  
Boguslaw Lipinski
Keyword(s):  
Fibrinolytic Activity ◽  
Degradation Products ◽  
Venous Occlusion ◽  
Protamine Sulfate ◽  
Electrophoretic Method ◽  
Soluble Fibrin ◽  
Fibrin Degradation Products ◽  
Fibrin Monomer ◽  
Derivatives Of

SummaryThe effect of naturally induced fibrinolytic activity on fibrinogen and certain soluble and insoluble derivatives was studied. Experiments were performed on blood removed after venous occlusion of the arm and immediately after death. A previously described electrophoretic method was used by which the heterogeneity of fibrinogen can be demonstrated directly in intact plasma. It was shown that fibrinogen, soluble fibrin monomer (FM) complexes and fibrin degradation products are resistant to degradation by naturally-induced fibrinolytic activity. By contrast, rapid lysis of fibrin, protamine sulfate (PS) precipitated fibrinogen, and PS and ethanol induced gels of FM occurred. The observations are believed relevant to our understanding of the pathway of fibrinogen and FM catabolism and the interpretation of the origin of serum FDP.

The Effect of Human Recombinant Tissue-Type Plasminogen Activator on Clinical and Laboratory Parameters of Hemostasis and Systemic Plasminogen Activation in the Dog and the Rat

1988 ◽  
Vol 60 (02) ◽  
pp. 271-279 ◽  
Author(s):  
John C Bloom ◽  
Teresa S Sellers ◽  
Gary C Gries ◽  
Eric B Wheeldon ◽  
Susan R O'Brien ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Degradation Products ◽  
Tissue Type ◽  
Fibrinogen Concentration ◽  
Plasminogen Activation ◽  
Post Mortem ◽  
Major Hemorrhage ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Dose Dependent

SummaryThe effect of human recombinant tissue-type plasminogen activator (rt-PA) on parameters of hemostasis and systemic plasminogen activation was studied in the dog and rat. Effects on screening coagulation times, fibrinogen concentration, fibrin/fibrinogen degradation products, and plasminogen and α2-anti- plasmin (α2-AP) activities in plasma were examined following single bolus injections of 0.5-5.0 mg/kg, single and repeated 3 hr infusions of 0.75-7.5 mg/kg and 24 hr infusions of 6.0 and 30.0 mg/kg administered intravenously to dogs. Rats receiving single or 14 daily injections of 5.0-30.0 mg/kg i.v. were similarly monitored. Systemic fibrinogenolysis (>50% decrease in fibrinogen, plasminogen or α2-AP values) was observed in dogs receiving ≥1.0 mg/kg as a bolus, ≥3.75 mg/kg (20.8 μg or 1.19 × 104 IU kg−1min−1) as a 3 hr infusion and >6 mg/kg (4.2 μg or 2.42 × 103IU kg−1min−1) as a 24 hr infusion; and in rats treated with bolus injections of 30 mg/kg rt-PA. Clinical and laboratory indications of impaired hemostasis and bleeding (anemia, prolonged coagulation times and post-mortem evidence of hemorrhage) were associated with these effects, which together were dose-dependent and influenced by the rate of infusion. The incidence of major hemorrhage was variable and limited to animals receiving prolonged (24 hr) or repeated infusions.

DETECTION OF SOLUBLE FIBRIN MONOMER COMPLEXES - COMPARISON OF A HAEMAGGLUTINATION ASSAY WITH THE ETHANOL GELATION TEST

1987 ◽  
Author(s):  
G Oehler ◽  
H Klaus ◽  
E Spanuth ◽  
K E Stötzer
Keyword(s):  
Degradation Products ◽  
Positive Test ◽  
Test Results ◽  
Soluble Fibrin ◽  
Fibrin Degradation Products ◽  
Fibrin Monomer ◽  
At Iii ◽  
Positive Results ◽  
Fibrin Monomers ◽  
Gelation Test

Hypercoagulability and disseminated intravascularcoagulation (DIC) are characterized by the presenceof circulating fibrin monomer complexes in plasma.In342 patients with possible DIC fibrin monomers, fibrinogen, reptilase time, antithrombin III and othercoagulation parameters were determined at frequent intervals.Testing of soluble fibrin monomer complexeswas performed using a sensitive and reliable haemagglut- ination assay, with red cells sensitized by fibrin monomers (FM-Test) and the ethanol gelation test(EGT). Method comparison regarding the influence offibrinogen levels and fibrin degradation products shows that high fibrinogen levels lead to false positive results with EGT. The same effect is observed forfibrin degradation products and EGT whereas no influence of fibrinogen level and fibrin degradation products on the FM-Test occurs.It could be shown that with normal fibrinogen concentrations (200-400 mg/dl) the positive test results by FMT and EGT are comparable, whereas with fibrinogen concentrations below 200 mg/dl the number of positive results obtained with the EGT amounted to half the number given by FMT. In the case of fibrinogen concentrations above 400 mg/dl, positive results obtained with EGT were 3.3 times higher than FMT. Nearlyidentical results were obtained by comparing the influence of degradation products. In case of high degradation product concentrations, EGT gives 4.5 timesmore positive results than FMT.Further we compared the number of positive test results obtained by the FMT with the level of AT III because it is wellknown that the AT IIIHevel decreases caused by proteolytic activity generated in DIC.In this study it could be shown that fibrin monomer increases in parallel with the decrease of AT III. Thiseffect does not occur with fibrin degradation products.

Measurement of soluble fibrin monomer-fibrinogen complex in plasmas derived from patients with various underlying clinical situations

2003 ◽  
Vol 89 (05) ◽  
pp. 832-836 ◽  
Author(s):  
Yumiko Kazahaya ◽  
Yuichi Shintani ◽  
Kensuke Yamazumi ◽  
Yutaka Eguchi ◽  
Shin Koga ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Disseminated Intravascular Coagulation ◽  
Degradation Products ◽  
Research Society ◽  
Distinct Entity ◽  
Soluble Fibrin ◽  
Intravascular Coagulation ◽  
Fibrin Degradation Products ◽  
Fibrin Monomer ◽  
D Dimer

SummaryWe previously reported a monoclonal antibody named IF-43 that specifically recognizes thrombin-modified fibrinogen (desAA- and desAABB- fibrin monomer) bound with fibrinogen or other D1 domain-containing plasmic fragments such as fragments X, Y, and D1, but not intact fibrinogen or cross-linked fibrin degradation products (XDP). Here, we tentatively named such complexes, soluble fibrin monomer (FM) -fibrinogen complex.By utilizing IF-43, we have developed a kit to measure soluble FM-fibrinogen complex and compared the profiles with those of two established molecular markers for thrombo-embolic disorders: i.e. the thrombin-antithrombin complex (TAT) and the D-dimer in plasma of patients who underwent surgery without any thrombo-embolic complications. The result indicated that soluble FM-fibrinogen complex is a distinct entity from the two established molecular markers. We have also attempted to observe their profiles in patients with the disseminated intravascular coagulation syndrome (DIC). Although the profiles of soluble FM-fibrinogen complex in individual patients appeared to vary from one patient to the other, the plasma level of soluble FM-fibrinogen complex was found to be increased at the initial phase of disseminated intravascular coagulation syndrome. Thus, the soluble FM-fibrinogen complex may serve as an independent molecular marker for the detection of thrombin generation and the diagnosis of thrombosis. The soluble FM-fibrinogen complex may also serve as a risk factor for thrombosis, because it may precipitate as insoluble complexes beyond its threshold in plasma, or when it is modified by thrombin.Part of this paper was originally presented at the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

DDE COMPLEX DETERMINATION AS A SPECIFIC MARKER FOR FIBRINOLYSIS

1987 ◽  
Author(s):  
J Soria ◽  
C Soria ◽  
Me Mirshahi ◽  
S Mirshahi ◽  
M Mirshahi ◽  
...  
Keyword(s):  
Degradation Products ◽  
Clinical Investigation ◽  
Polyacrylamide Gel Electrophoresis ◽  
Tissue Type ◽  
Specific Marker ◽  
Fibrin Degradation Products ◽  
Pathological Conditions ◽  
Fibrin Monomer ◽  
Type Plasminogen Activator ◽  
Conventional Elisa

Monoclonal antibodies (McAb) reacting with fibrin degradation products (FbDP), but not with fibrinogen have been produced in order to determine specifically FbDP directly in plasma. Most of the McAb available however do also react with fragment D. Our anti D neo McAb reacts about 10 times less with fragment D than with FbDP but does not react with fibrinogen, fragment X or Y.In clinical investigation, even in pathological conditions in which there is a great release of tissue-type plasminogen activator (tpA), we have shown that fragment D is not generated in patients plasma. Therefore, the reactivity of our McAb with fragment D did not alter the specificity of FbDP assay.On the contrary, using polyacrylamide gel electrophoresis in the presence of SDS followed by immunorevelation, we have evidenced that fragment D is generated in patients undergoing thrombolytic therapy even with rtpA. Therefore, using conventional Elisa procedure (capture of FbDP on polystyrene-immobilized anti D neo antibody and detection by peroxidase-labelled anti fragment D immunoglobulins), the presence of fragment D in patients plasma leads to an overevaluation of FbDP. To avoid this overestimation we have modified the Elisa procedure. The structure of FbDP was taken into acount in order to render the technique specific of FbDP. In FbDP fragment D coming from one fibrin monomer is always associated with fragment E from another fibrin monomer, as DDE complex for example. Therefore after capture of fragment D by the polystyrene-bound anti D neo McAb, FbDP were specifically revealed by peroxidase-labelled anti E antibody (polyclonal or monoclonal anti E may be used). For this reason, this test was named DDE determination and DDE determination can be used in any circumstances to evaluate fibrin degradation.

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