Gastric Fibrinolysis

1975 ◽  
Vol 34 (02) ◽  
pp. 409-418 ◽  
Author(s):  
I. M Nilsson ◽  
S.-E Bergentz ◽  
U Hedner ◽  
K Kullenberg
Keyword(s):  
Gastric Ulcer ◽  
Gastric Juice ◽  
High Activity ◽  
Fibrinolytic Activity ◽  
Duodenal Juice ◽  
Bleeding Tendency ◽  
Local Fibrinolysis ◽  
Heated Plates

SummaryGastric juice from 15 normals, 20 patients with gastric ulcer and 4 patients with erosive haemorrhagic gastroduodenitis was investigated in respect of its activity on unheated and heated fibrin plates and its content of FDP and plasminogen or plasmin with immunochemical methods. Gastric juice from normals showed no activity on unheated and heated fibrin plates, and no FDP or plasminogen could be demonstrated. In the patients with gastric ulcer the gastric juice showed little or no fibrinolytic activity on fibrin plates except in 2, who had regurgitation of duodenal juice and neutral pH of the juice. These patients had equally high activity on heated as on unheated plates and no plasmin could be demonstrated. It was shown that this activity was not due to fibrinolysis, but to non-specific proteolytic activity (probably trypsin). The patients with erosive haemorrhagic gastroduodenitis exhibited quite a different picture. The gastric juice from these patients showed extremely high activity on fibrin plates, the activity was higher on unheated than on heated plates. The activity was inhibited in vitro by addition of EACA and in vivo after administration of AMCA. The occurrence of plasmin could be demonstrated directly immunologically in the gastric juice. By comparison of plasmin and trypsin in various assays it could further be proved that the gastric juice in these cases contained plasminogen activator and plasmin. The patients with erosive haemorrhagic gastroduodenitis showed no increase in fibrinolysis in the blood, but low values for plasminogen and α2M, and the serum contained FDP. These findings in the blood and gastric juice were interpreted as signs of local fibrinolysis in the stomach and duodenum. There is reason to assume that this gastric fibrinolysis contributes substantially to the bleeding tendency. The effect of administration of AMCA on fibrinolytic activity and the haemorrhage lends support to the assumption of such a mechanism.

Coagulation Studies in a Case of Hageman Trait

1961 ◽  
Vol 05 (02) ◽  
pp. 187-200 ◽  
Author(s):  
E. A Loeliger ◽  
A Hensen
Keyword(s):  
High Activity ◽  
Blood Coagulation ◽  
Fibrinolytic Activity ◽  
Coagulation Factors ◽  
Normal Rate ◽  
Hageman Factor ◽  
Haemorrhagic Diathesis ◽  
Anticoagulant Property

SummaryAfter a brief review of the data concerning the cases of Hageman trait hitherto reported in the literature, a patient with severe Hageman factor (HF) “deficiency” (HF-activity below 0.05% of normal) is described. The patient has no haemorrhagic diathesis.In vitro, intrinsic coagulability and fibrinolytic activity are grossly disturbed. On the basis of a diminished fibrinolytic activity in vivo, the rather high activity of several coagulation factors in patient’s plasma could be explained.Thromboplastin formation, once initiated, is normal as to rate; the amount of thromboplastin formed is possibly slightly diminished. Prothrombin consumption is normal. These findings are in agreement with a normal rate ot clot formation, as measured by means of thrombelastography.Normal HF seems to be an initiator of blood coagulation only and not an activator or a substrate involved in thromboplastin formation.The weak anticoagulant property of Hageman trait plasma, described by several authors, is not necessarily due to an inhibitor; it can be explained by the assumption that, in Hageman trait, HF shows normal glass adsorbability and only a very deficient glass activation.

High Level of Fibrinolysis and Low Factor XIII in Erosive Haemorrhagic Gastroduodenitis

1975 ◽  
Author(s):  
I. M. Nilsson ◽  
S.-E. Bergentz ◽  
U. Hedner
Keyword(s):  
Platelet Count ◽  
Gastric Juice ◽  
Fibrinolytic Activity ◽  
Factor Xiii ◽  
Proteolytic Enzymes ◽  
Bleeding Tendency ◽  
Erosive Gastritis ◽  
Local Fibrinolysis ◽  
High Level ◽  
Gastrointestinal Canal

Erosive haemorrhagic gastroduodenitis was found to be combined with high fibrinolytic activity of the gastric juice. This activity was due to a plasmin-like enzyme and not to other gastric proteolytic enzymes. No increase in fibrinolytic activity could be demonstrated in blood, but the values found for fibrinogen, plasminogen and α2M were low. A high content of FDP was found in serum. A markedly decreased content of factor XIII was found with the dansylcadaverine method. Platelet count and other coagulation components were normal. These findings were interpreted as local fibrinolysis in the diseased parts of the gastrointestinal canal. The bleeding stopped after administration of A MCA (Cyclo-kapron® ) and factor XIII concentrate. The results indicate that the high local fibrinolytic activity in the stomach together with the low content of factor XIII contributes substantially to the increased bleeding tendency in erosive gastritis. This may lead to a revision of the treatment of such cases.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

The Effects of Some Synthetic Compounds on In Vitro Fibrinolytic Activity Measured by Different Methods and the Relevance to Activity In Vivo

1972 ◽  
Vol 28 (03) ◽  
pp. 351-358
Author(s):  
A.J Baillie ◽  
A. K Sim
Keyword(s):  
Inhibitory Activity ◽  
Substrate Concentration ◽  
Fibrinolytic Activity ◽  
Synthetic Compounds ◽  
In Vitro Methods ◽  
Narrow Concentration Range

SummaryThe activity of several synthetic compounds, rated from good to poor (or inactive) fibrinolytic activators, has been assessed by two different commonly-used in vitro methods. Compounds shown to be active over a narrow concentration range in the hanging clot test were shown to be inhibitors of plasmin and trypsin in the casein-olytic test. The inhibitory activity of these compounds was shown to increase with increasing substrate concentration and apparent activity in the hanging clot test. Possible explanations and relevance of these observations are discussed.

Preparation Of Antithrombin, High Activity Heparin And A Heparin-Antithrombin Complex By A Rapid Two-Step Affinity Method

1981 ◽  
Author(s):  
R Jordan ◽  
T Zuffi ◽  
M Fournel ◽  
D Schroeder
Keyword(s):  
Ionic Strength ◽  
High Activity ◽  
Tight Binding ◽  
Therapeutic Benefit ◽  
Purification Scheme ◽  
The Matrix ◽  
Low Ionic Strength ◽  
Potential Therapeutic Benefit

The tight binding affinity of antithrombin for heparin makes possible a relatively selective purification scheme based on salt elution from heparin-Sepharose. We have found, however, that purity can often be greatly increased if the elution is carried out with soluble heparin instead. This heparin can be removed from the antithrombin, either in whole or part, by a second affinity step on Concanavalin A Sepharose. The antithrombin, which binds to the matrix through its glycosidic moieties, retains its ability to bind heparin at physiological ionic strengths. Thus, the complex of antithrombin and heparin is readily isolated free of unbound heparin species. The complex can be eluted intact with low ionic strength buffers containing sugars which compete for binding to the lectin. Alternatively, the high activity heparin (400–500 units/mg) can be obtained separately by a 1 M NaCl wash which is then followed by a carbohydrate wash to obtain the purified antithrombin.We have made certain preliminary biochemical and anticoagulant characterizations of these materials. Not unexpectedly, both the high activity heparin and its complex with antithrombin show significantly greater in vitro potency in comparison to unfractionated heparin. In vivo anticoagulant efficacy, as evaluated in a rabbit infusion model, confirmed the in vitro findings and further suggests some potential therapeutic benefit may be derived from infusion of a preformed heparin-antithrombin complex.

Pathogenesis of Fibrinolysis in Defibrination Syndrome: Effect of Heparin Administration

Blood ◽  
1964 ◽  
Vol 24 (6) ◽  
pp. 701-715 ◽  
Author(s):  
CLARENCE MERSKEY ◽  
ALAN J. JOHNSON ◽  
JAMES H. PERT ◽  
HERBERT WOHL
Keyword(s):  
Warfarin Therapy ◽  
Blood Platelets ◽  
Factor V ◽  
Normal Limits ◽  
Heparin Administration ◽  
Fibrinolytic Inhibitors ◽  
Local Fibrinolysis

Abstract 1. Spontaneous local fibrinolysis occurred with, and was probably a consequence of thrombosis, with defibrination in vivo. 2. The efficacy of heparin in the prevention of defibrination was clearly demonstrated; warfarin therapy seemed to be ineffective. 3. The efficacy of heparin in the prevention of the associated fibrinolysis was clearly inferred. 4. Serum immunoelectrophoresis against anti-fibrinogen sera demonstrated abnormal precipitin bands, during defibrination and fibrinolysis, which disappeared during heparin administration. 5. The serum bands showed immunologic identity with in vitro plasmin digests of fibrinogen and the intensity and position of these precipitin bands appeared to depend on the amount of fibrinogen and the duration of the in vivo digestion period. 6. In this hypofibrinogenemic state, defibrination was indicated by markedly reduced levels of anti-hemophilic factor and Factor V and a fall in blood platelets. The presence of fibrinolysis was shown by the lowered levels of plasminogen, streptokinase and urokinase inhibitors, prolonged thrombin clotting times and fibrinolytic breakdown products in the serum even though little or no lysis occurred on fibrin plates and the euglobulin lysis times were within normal limits. 7. The administration of fibrinolytic inhibitors is strongly contraindicated under these circumstances.

scholarly journals "Impotent" Platelets in Albinos With Prolonged Bleeding Times

Blood ◽  
1972 ◽  
Vol 39 (4) ◽  
pp. 490-499 ◽  
Author(s):  
Harold M. Maurer ◽  
James A. Wolff ◽  
Sue Buckingham ◽  
Arthur R. Spielvogel
Keyword(s):  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Bleeding Tendency ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time ◽  
Normal Platelet ◽  
Tryptophan Metabolites ◽  
History Of

Abstract Functional, biochemical, and morphologic platelet abnormalities are reported in four children with the syndrome of albinism, mild bleeding tendency, prolonged bleeding time, and normal platelet count. In these children, primary platelet aggregation with adenosine diphosphate occurred normally, but secondary aggregation was impaired. Collagen and norepinephrine produced almost no platelet aggregation. Platelet content of serotonin (5-HT) was markedly reduced, and uptake and retention of 5-HT by the platelets in vivo and in vitro was poor. In one child who was given a tryptophan load, urinary tryptophan metabolites were normal, suggesting that there was no evidence of a block in the 5-HT synthetic pathway in the gastrointestinal tract. Electron microscopy revealed an absence of densely osmophilic granules in 5-HT poor platelets. Platelets from other albinos with no history of bleeding contained normal amounts of 5-HT and densely osmophilic granules.

scholarly journals Improved Antithrombotic Activity and Diminished Bleeding Side Effect of a PEGylated αIIbβ3 Antagonist, Disintegrin

Toxins ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 426
Author(s):  
Yu-Ju Kuo ◽  
Yao Tsung Chang ◽  
Ching-Hu Chung ◽  
Woei-Jer Chuang ◽  
Tur-Fu Huang
Keyword(s):  
Platelet Aggregation ◽  
Side Effect ◽  
Half Life ◽  
Platelet Rich Plasma ◽  
Drug Stability ◽  
Severe Thrombocytopenia ◽  
Bleeding Tendency ◽  
Dependent Manner

Polymer polyethylene glycol (PEG), or PEGylation of polypeptides improves protein drug stability by decreasing degradation and reducing renal clearance. To produce a pharmaceutical disintegrin derivative, the N-terminal PEGylation technique was used to modify the disintegrin derivative [KGDRR]trimucrin for favorable safety, pharmacokinetic profiles, and antithrombotic efficacy. We compared intact [KGDRR]trimucrin (RR) and PEGylated KGDRR (PEG-RR) by in vitro and in vivo systems for their antithrombotic activities. The activity of platelet aggregation inhibition and the bleeding tendency side effect were also investigated. PEG-RR exhibited optimal potency in inhibiting platelet aggregation of human/mouse platelet-rich plasma activated by collagen or ADP with a lower IC50 than the intact derivative RR. In the illumination-induced mesenteric venous thrombosis model, RR and PEG-RR efficaciously prevented occlusive thrombosis in a dose-dependent manner. In rotational thromboelastometry assay, PEG-RR did not induce hypocoagulation in human whole blood even given at a higher concentration (30 μg/mL), while RR slightly prolonged clotting time. However, RR and PEG-RR were not associated with severe thrombocytopenia or bleeding in FcγRIIa-transgenic mice at equally efficacious antithrombotic dosages. We also found the in vivo half-life of PEGylation was longer than RR (RR: 15.65 h vs. PEG-RR: 20.45 h). In conclusion, injectable PEG-RR with prolonged half-life and decreased bleeding risk is a safer anti-thrombotic agent for long-acting treatment of thrombus diseases.

Independence of activation of the fibrinolytic system from certain immunologic systems

1959 ◽  
Vol 196 (2) ◽  
pp. 431-435 ◽  
Author(s):  
S. N. Kolmen ◽  
D. R. Celander ◽  
M. Mason Guest
Keyword(s):  
Fibrinolytic Activity ◽  
Complement Fixation ◽  
Fibrinolytic System ◽  
Complement Activity ◽  
Antibody Reaction ◽  
Antigen Antibody

Activation of the immunologic system either in vitro or in vivo results in nearly complete consumption of complement without activation of the fibrinolytic system. However complement activity decreased upon the induction of fibrinolytic activity even in the absence of an antigen-antibody reaction. Presumably this is due to proteolysis of some part of the complement complex since complement activity was found to be destroyed in the presence of small quantities of purified fibrinolysin. These observations are consistent with the conclusion that a) the components of complement and those of the fibrinolytic system are separate and discrete entities; b) that reactions involving complement fixation and activation do not directly influence the fibrinolytic system; and c) that activation of the fibrinolytic system results in decreases in complement through proteolysis of one or more of its components by the fibrinolysin which develops.

Some Observations on the Effect of Digestive Juices on Scolices ofEchinococcus granulosus(Batsch).

1936 ◽  
Vol 14 (1) ◽  
pp. 21-40 ◽  
Author(s):  
D. A. Berberian
Keyword(s):  
Gastric Juice ◽  
Intestinal Tract ◽  
Time Intervals ◽  
Human Gastric Juice ◽  
Rate Of Development ◽  
Single Cyst ◽  
Intestinal Juice ◽  
Definite Time

Experimentsin vivoandin vitroare reported on the action of digestive juices of various animals on the scolices ofE. granulosus. Inin vitrostudies, scolices ofE. granulosuswere placed in the digestive juices of different animals, incubated at 37°C., and the digestive action of the fluids was studied by examining portions of the material under the microscope.In vivoexperiments were carried out on kittens, rats and rabbits. These animals were fed large quantities of scolices of hydatid cyst membranes and they were killed at definite time intervals and their intestinal tract was carefully examined for scolices.Gastric juice of rats, dogs, cats, sheep and cattle did not digest scolices. The action of the gastric juice of rabbits begins late and proceeds slowly. Human gastric juice causes incomplete digestion and acts only on the evaginated scolices.The intestinal juices of man, rats, rabbits, sheep and cattle are able to digest scolices completely, whereas the intestinal juice of dogs and cats is inactive. In spite of the fact that cat intestinal juice is inactive, kittens are found to be slightly susceptible. Since they suffer only relatively light infestation and the rate of development is retarded, we would classify the cat as an “abnormal” host toE. granulosus.Time of evagination of scolices from a single cyst or from cysts from different animals is variable. Some scolices evaginate readily, others more slowly and still others fail to evaginate completely.

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