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PubMedDate not supplied

[Fibrinolytics and defibrinating agents].

Therapeutic fibrinolysis represents the only logical means of curing thromboses, by assuring the destruction of the thrombus. This kind of therapy, which was introduced clincally over 10 years ago, has been used on only a limited scale because of the high risk of haemorrhage and the need for highly specialized laboratory control tests. Different methods of administration, overcoming one or other of these disadvantages, have resulted recently in its wider use but this has been accompanied by a reduction in efficacity. The very satisfactory clinical results obtained in some cases remain limited and thus in this context the indications should not be restricted.

Batroxobin↗
PubMed1975

Determination of human fibrinopeptide A by radioimmunoassay in purified systems and in the blood.

The formation of fibrin clots or circulating soluble fibrin is accompanied by the appearance of fibrinopeptides. Measurement of the fibrinopeptide concentration in plasma can provide important information on the rate of conversion of fibrinogen to fibrin by thrombin. This rate varies under different physiologic and pathologic conditions. Fibrinopeptide A is a better molecular marker of the conversion than fibrinopeptide B since it is the first peptide to be cleaved by thrombin. A radioimmunoassay technique has been developed for the quantitative determination of human fibrinopeptide A. The procedure detects human fibrinopeptide A at a concentration of approximately 0.05 ng/ml. The variation of fibrinopeptide A content in normal persons may reflect its rapid formation and catabolism. A significantly increased concentration of this peptide was found in a patient during defibrination therapy with a purified enzyme from the venom of Agkistrodon rhodostoma and in patients suffering from retinal vascular occlusions.

Amino Acid Sequence↗
PubMed2002

Effect of electroporation and iontophoresis on skin permeation of Defibrase--a purified thrombin-like enzyme from the venom of Agkistrodon halys ussuriensis Emelianov.

The purpose of this study was to investigate electroporation and iontophoresis as a means for in vitro delivery of Defibrase--a thrombin-like enzyme (TLE) from Agkistrodon halys ussuriensis Emelianov snake venom--through human epidermis membrane (HEM). Electroporation was carried out using an exponential decay pulse generator (BioR-ad Genepulser, USA) for a period of 0.5 h, followed by a period of 5.5 h passive diffusion or iontophoresis. The results indicated that the combined use of electroporation and anodal iontophoresis in pH 6.4 permeation medium could effectively enhance the skin permeation of Defibrase, whose apparent permeability coefficient was 1.6 +/- 0.8 x 10(-4) cm.h-1. The delivery of Defibrase by the combined use of electroporation and anodal iontophoresis was more effective than by electroporation alone (P < 0.01) or by the combined use of electroporation and cathodal iontophoresis (P < 0.01). Moreover, when the pH of the permeation medium was raised from 6.4 to 7.4 the permeation of Defibrase caused by a combined use of electroporation and anodal iontophoresis showed a tendency to increase. These results implied that electroosmotic flow effect might be important for the iontophoretic (following electroporation) skin permeation of Defibrase.

Batroxobin↗
PubMed2002

[Hemocoagulase in abdominal operation and its effect on hemoagglutination].

OBJECTIVE: To evaluate the hemostatic role of hemocoagulase in abdominal operation and its effects on coagulation. METHODS: 180 patients receiving abdominal operation were studied prospectively by randomized, double-blind controlled and multicenter design. They were divided into Hemocoagulase group (60 patients), lizhixue group (60), and manitol hexanitrate group (60). The groups were, observed in terms of the effects on hemostatic time, hemorrhagic volume, hemorrhagic volume per square unit, and body coagulation (BT, CT, PT, APTT and PLT) parameters. RESULTS: The groups received different drugs. The average hemostatic time in the hemocoagulase group was 121.6 s, hemorrhagic volume was 9.6 g, and hemorrhagic volume per square unit was 0.2 g. The similar results were observed in the lizhixue group (P > 0.05), but they were significantly different (P < 0.05) from those of the manitol hexanitrate group (159.2 s, 12.49 g, 0.3 g). In the hemocoagulase and lizhixue groups hemorrhagic and hemoagglution time decreased 30 minutes and 1 day after operation. This finding was significantly differenct from that in the manitol hexanitrate group (P < 0.05). CONCLUSION: Hemocoagulase plays a good hemostatic role in the hemorrhagic capillary at abdominal incision.

Abdomen↗
PubMed2003

Different mechanisms contribute to the biphasic pattern of carboxypeptidase U (TAFIa) generation during in vitro clot lysis in human plasma.

Carboxypeptidase U (CPU,TAFIa) recently gained interest as a significant player in dampening the fibrinolytic rate. The aim of this study was to investigate the time course of the generation of CPU activity during coagulation and fibrinolysis using an in vitro clot lysis model in human plasma. A first peak of CPU activity appeared after initiation of the coagulation phase and a second rise in CPU activity was observed during the fibrinolysis. The decrease in the proCPU plasma concentration followed the same trend as the appearance of the CPU activity. The direct thrombin inhibitor inogatran eliminated the CPU generation during coagulation but not during fibrinolysis. Addition of the plasmin inhibitor aprotinin during fibrinolysis resulted in a decrease in CPU activation during the lysis phase. These results demonstrate that proCPU was activated during coagulation by thrombin and during fibrinolysis by plasmin. Addition of a CPU inhibitor before initiation of clotting decreased the clot lysis time as expected. However, addition in the time period between the two peaks of CPU activity had no apparent effect on the clot lysis time.

Amino Acid Chloromethyl Ketones↗
PubMed1976

Induction of endogenous fibrinolysis inhibition in the dog. Effect of intravascular coagulation and release of free fatty acids.

Possible mechanisms underlying the development of fibrinolysis inhibition following trauma were studied. In order to investigate the role of intravascular coagulation dogs were subjected to infusions of thrombin or endotoxin, which both caused an increase in urokinase inhibitor activity in serum after 24 and 48 hours. The inhibitor increase following thrombin infusion was not, however, prevented by previous defibrinogenation with Defibrase or by induction of thrombocytopenia with antiplatelet serum, suggesting that neither platelets nor fibrinogen are necessary for the post-traumatic occurrence of fibrinolysis inhibition. In all groups subjected to infusion of thrombin an increase in plasma free fatty acids (FFA) was observed. The role of this increase for the development of fibrinolysis inhibition was tested by infusion of norepinephrine alone and in combination with nicotinic acid. Norepinephrine caused an increase of FFA after 2 hours and in urokinase inhibitor activity after 24-48 hours. Both of these were diminished by high doses of nicotinic acid, indicating that the release of FFA rather than intravascular coagulation might be the principal mechanism underlying the occurrence of fibrinolysis inhibition following trauma.

Animals↗
PubMed1976

Comparison of a direct latex-agglutination technic with the tanned red cell hemagglutination inhibition immunoassay (TRCHII) for semiquantitation of fibrinogen/fibrin degradation products.

A new latex-agglutination kit for rapid screening for fibrinogen/fibrin degradation products (FDP/fdp) has been compared with a standard tanned red cell hemagglutination inhibition immunoassay (TRCHII). The latex-agglutination test results agreed with the TRCHII results for 489 of 588 samples (83%). FDP/fdp values were elevated by the latex-agglutination kit when normal by the TRCHII for 79 (13%) samples, and the reverse was true for 20 (3%) samples. Serial dilution of serum sample allowed reliable semiquantitation of FDP/fdp levels compared with TRCHII results (r=less than .001). The latex-agglutination test gave FDP/fdp values of larger than or equal to 10 mug. per ml. for sera from 11 of 13 patients who had acute pulmonary embolism and for only one of 24 normal control samples. The direct latex-agglutination kit for FDP/fdp appears to have appropriate sensitivity to serve as a screening test for acute pulmonary embolism in patients not receiving heparin therapy.

Batroxobin↗
PubMed1992

Thrombolytic actions of reptilase.

In thrombolytic model in vitro, reptilase (Rep, defibrase) did not show appreciable thrombolytic actions on red and white thrombi. After daily iv infusion of Rep 0.25 IU for 10 d, the time of 50% lysis of euglobulin (ELT1/2) was shortened from 9.3 +/- 0.8 to 6.7 +/- 1.0 h (P < 0.01), alteplase activity was increased from 1.9 +/- 0.7 to 3.7 +/- 0.9 IU.ml-1, and plasminogen inactivator (PI) activity reduced from 4.3 +/- 0.6 to 1.8 +/- 0.9 AU.ml-1 (all P < 0.01). The findings indicate that the thrombolytic action of Rep shown in vivo may not be from the direct action on thrombi but from the influence on alteplase and PI activity.

Adult↗
PubMed1976

Detection of soluble intermediates of the fibrinogen-fibrin conversion using erythrocytes coated with fibrin monomers.

The presence of minimal amounts of fibrinogen-fibrin intermediates in human plasma was visualized by an agglutination reaction of glutaraldehyde-treated human erythrocytes coated with purified fibrin monomers. A degree of monomer coating was established which produced erythrocytes not agglutinated by normal plasma but by plasma containing minimal amounts of soluble complexes of fibrinogen with fibrin monomers. Under standardized conditions of coating, erythrocyte concentration, temperature, pH, and incubation time, the agglutination time varied with the ratio of soluble fibrin to fibrinogen in plasma. The test was sensitive down to a soluble fibrin concentration of 0.675% of the plasma fibrinogen concentration. Early fibrinogen and fibrin degradation products (FDP) in the plasma led to a prolongation of the agglutination time at a concentration of more than 16 mg/100 ml. Late FDP in a concentration of 100 mg/100 ml did not convert a positive test to negative. The test was not affected by heparin and protamine at concentrations of up to 12.5 and 50 NIH units/ml, respectively.

Batroxobin↗