Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secondary generalized hyperfibrinolysis was induced by thrombin infusion or batroxobin injection in rats. To follow intravascular fibrinolysis quantitatively, an electroimmuno-assay was used for determination of the fibrin degradation products formed. Anticoagulants (heparin, hirudin), antifibrinolytics (EACA, PAMBA, AMCA), and synthetic (APPA) and naturally occurring (aprotinin) protease inhibitors were studied with regard to their influence on secondary fibrinolysis. The potency and duration of action of the antifibrinolytics tested correspond to their antifibrinolytic activity measured in vitro and to their pharmacokinetics. Formation of degradation products is initiated after the appearance of fibrin monomer or fibrin, respectively. Due to their antithrombin action heparin, hirudin, and APPA prevent the thrombin-induced fibrin formation and thus the induction of secondary fibrinolysis. In contrast, formation of fibrin monomers caused by batroxobin is not influenced by thrombin inhibitors so that in this case formation of degradation products is not prevented.
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PMID:[Pharmacologic influence on secondary generalized fibrinolysis]. 53 98

Fibrin formation from fibrin monomer (FM) complexes was studied in experimental animals utilizing a previously described technique for quantitating fibrin deposition. A uniform thrombin infusion was used to produce FM, fibrinolysis being inhibited by EACA. In vivo complex formation between FM and 125I-fibrinogen was demonstrated chromatographically. A direct correlation was found between blood fibrinogen concentration and fibrin deposition in organs. By contrast, an inverse correlation between fibrinogen concentration and both enzymatic or non-enzymatic fibrin formation was found in vitro. The mechanism by which fibrinogen potentiates FM precipitation in vivo could not be explained by coprecipitation of fibrinogen in the complex which could not be demonstrated. The inhibitory effect of HN2 on fibrin deposition despite the associated hyperfibrinogemia induced by this drug is believed to underscore the importance of leukocytes in certain types of fibrin deposition. A correlation between the leukocyte count and fibrin formation from FM was also found. It was concluded that the risk of intravascular fibrin deposition is increased by a raised fibrinogen level especially when accompanied by leukocytosis.
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PMID:The effect of the fibrinogen concentration and the leukocyte count on intravascular fibrin deposition from soluble fibrin monomer complexes. 103 54

Intravascular fibrin deposition was induced in rabbits by endotoxin, the infusion of fibrin monomer (FM), and by the infusion of thrombin and EACA. A previously developed radioisotope technique was used to measure the fibrin deposits in various organs. Dipyridamole treatment of rabbits caused significant inhibition of fibrin deposition in all three experimental models. The drug also inhibited platelet consumption and, in the thrombin- and EACA-infused animals, fibrinogen consumption as well. The results obtained with dipyridamole were compared with the effect of thorotrast. It was concluded from this comparison that the effect of dipyridamole could not be attributed to inhibition of the reticuloendothelial system. It is postulated that dipyridamole inhibits the final step at which soluble FM is precipitated as fibrin in vivo.
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PMID:Inhibition of intravascular fibrin deposition by dipyridamole in experimental animals. 109 Mar 12

In this presentation we have contrasted the normal blood-clotting mechanism with the failure to form blood clots in hemophiliacs due to the absence of protein factors necessary for conversion of prothrombin to thrombin. The statistics, hereditary basis, and long-term disabling consequences of hemophilia to the severely ffected patient are described. The systemic means of minimizing severe joint disabilities and serious internal bleeding hazards by employing concentrates of antihemophilic factors to reverse the bleeding defects are discussed. Availability and advantages of the types of concentrates are explained. The fatalistic attitude of hemophiliacs toward hepatitis is discussed, along with admonitions to avoid the use of aspirin, alcohol, and buttock injections. Alternative medications for pain are recommended; and injection sites for pediatric patients are suggested. The details of simplified oral surgical management of hemophilic patients without hospitalization are described, including local anesthetic injection technique, method of performing extractions, general anesthesia techniques when indicated, materials for packing of extraction sockets, regimen and precautions in use of Amicar administration for clot maintenance, postoperative diet, and postsurgical activity guidelines. Also noted is the self-administration of intravenous concentrate infusions at home in the event of hemorrhagin, so that bleeding is on the way to bein controlled even before the patient reaches the hospital. We avoided orthodontic treatment of hemophilic patients in the past; however, recently developed bracket-fixation techniques and auxiliary aids; along with an enlightened understanding that gingival bleeding is ot to be feared, have changed our attitude, and we now treat hemophilic patients in much the same manner as otherwise normal orthodontic patients...
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PMID:Orthodontics and dentistry for the hemophilic patient. 110 95

The fibrinolytic activity was studied in 7 haemophiliacs, in comparison with 5 normals and 7 patients with disseminated intravascular coagulopathy, by determining the level of the fibrin(ogen) degradation products (FDP) in samples obtained as sera, clotting occurring naturally, and samples obtained as plasma and converted into serum by addition of thrombin-EACA. It was found that in haemophiliacs serum samples had normal FDP levels while plasma converted to serum showed high levels. This was explained by the fibrinolytic action of thrombin. Fibrinolysis was not prevented by EACA present due to the fact that it is an inhibitor of the plasminogen system but not of thrombin.
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PMID:Fibrinolytic activity in haemophiliacs. 123 Mar 52

In the present study we have quantitatively characterized the interaction of purified human Glu- and Lys-plasminogen with intact and degraded fibrin by ligand-binding experiments using a radioisotopic dilution method and antibodies against human plasminogen. A fibrinogen monolayer was covalently linked to a solid support with polyglutaraldehyde and was treated with thrombin or with thrombin and then plasmin to respectively obtain intact and degraded fibrin surfaces. Under these conditions, a well-defined surface of fibrin is obtained (410 +/- 4 fmol/cm2) and, except for a 39-kDa fragment, most of the fibrin degradation products remain bound to the support. New binding sites for plasminogen were detected on the degraded surface of fibrin. These sites were identified as carboxy-terminal lysine residues both by inhibition of the binding by the lysine analogue 6-aminohexanoic acid and by carboxy-terminal end-group digestion with carboxypeptidase B. The binding curves exhibited a characteristic Langmuir adsorption isotherm saturation profile. The data were therefore analyzed accordingly, assuming a single-site binding model to simplify the analysis. Equilibrium dissociation constants (Kd) and the maximum number of binding sites (Bmax) were derived from linearized expression of the Langmuir isotherm equation. The Kd for the binding of Glu-plasminogen to intact fibrin was 0.99 +/- 0.17 microM and for degraded fibrin was 0.66 +/- 0.22 microM. The Kd for the binding of Lys-plasminogen to intact fibrin was 0.41 +/- 0.22 microM and for degraded fibrin was 0.51 +/- 0.12 microM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of the binding of plasminogen to fibrin surfaces: the role of carboxy-terminal lysines. 167 72

Because fibrinolysis is now recognized as an important factor in hypercoagulable states, we have developed and characterized an easily performed, rapid, and quantitative screening test that assesses a patient's fibrinolytic activity. This modification of the dilute whole blood clotting time (DWBCT) counts the number of intact erythrocytes released from the clot formed in samples obtained before and after the application of a venous occlusion cuff. Samples were corrected for the plasma volume changes that occurred during venous occlusion. This test was performed on nine healthy volunteers. Specimens were diluted 1:1 with PBS, rapidly clotted with thrombin and incubated at 37 C. Starting thirty minutes after the thrombin was added and then at twenty minute intervals until 110 minutes, the number of RBCs released from the clot were counted using a Coulter S Plus counter. There were consistently more RBCs released at each time period after venous occlusion (p less than 0.001). Aliquots were also obtained for measuring PAI activity and TPA levels. PAI activity was lower post-cuff at every point (p less than 0.001). TPA level was higher at every point (p less than 0.001) post-cuff. The addition of exogenous TPA, activated protein C, or anti-PAI antibodies increased the amount of clot lysis; while the addition of anti-TPA antibodies and EACA each prevented the post-cuff increase. Unlike the euglobulin lysis time (ELT) this modified DWBCT (mDWBCT) measures the patients intact fibrinolytic system, including PAI and erythrocytes, in a quantitative fashion. Unlike either the ELT or the DWBCT the mDWBCT can be performed within two hours, so results are rapidly available for clinical decisions. These studies have demonstrated an easily performed, inexpensive, quantitative screening test of a patient's overall fibrinolytic system that reacts appropriately to pharmacologic manipulations.
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PMID:A modified quantitative whole blood clot lysis method for general laboratory analysis of fibrinolysis. 211 74

This report describes a method of bleeding control at dental extraction sites using medicaments (thrombin, cocaine, Amicar, Surgicel) in conjunction with a dental appliance containing vinyl polysiloxane silicone putty (Optosil) to provide greater coverage and pressure at the extraction sites. The acrylic splint was used to control bleeding in a 15-year-old male, with an aplastic pancytopenia anemia, who had required removal of severely mobile exfoliating teeth prior to a bone marrow transplantation procedure.
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PMID:Bleeding control after extractions in a patient with aplastic anemia during bone marrow transplantation: report of case. 264 46

In this report we used a fluorescent flow cytometry-based assay to examine plasminogen binding to platelets in plasma. Our data indicate that platelets activated in platelet-rich plasma (PRP) by adenosine-5'-diphosphate (ADP) or thrombin bind plasminogen to their surface. Fab fragments of the monoclonal antibody LJ-CP8 that are directed against the fibrinogen binding site on the glycoprotein (GP) IIb-IIIa complex inhibit both plasminogen and fibrinogen binding to ADP-stimulated platelets as does 5 mmol/L EDTA. Platelet aggregation and plasminogen and fibrinogen binding are also concurrently inhibited by the Gly-Arg-Asp (RGD) analogue Gly-Arg-Gly-Asp-Ser (GRGDS) when it is added to PRP before ADP stimulation. The scrambled peptide analogue SDGRG has no effect. The monoclonal antibody 6D1, directed against the von Willebrand factor binding site on GPIb, has no effect on plasminogen-platelet binding, nor does antithrombospondin antibody. epsilon-Aminocaproic acid (EACA), however, inhibits plasminogen binding to ADP-activated platelets. These data indicate that plasminogen binds to platelets activated in plasma, that binding occurs on platelet GPIIb/IIIa, and that binding may be mediated via plasminogen association with fibrinogen via lysine binding domains. Finally, we found both plasminogen and fibrinogen on resting platelets in PRP and demonstrated that they are equally displaced by EDTA, LJ-CP8, and 10E5 (an additional anti-GPIIb/IIIa monoclonal antibody). Plasminogen is also equally displaced by EACA. These data suggest that plasminogen is also bound to GPIIb/IIIa on resting platelets, possibly also via interaction with fibrinogen.
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PMID:Plasminogen interactions with platelets in plasma. 317 39

Pathogenesis of the microthrombi produced during intravascular coagulation was investigated in rabbits given intravenous infusions of thrombin or adenosine diphosphate (ADP). Thrombin, at a dosage producing a fibrinogen consumption of 70% within 4 h (1 unit/kg/min), failed to produce extrapulmonary microthrombi unless fibrinolysis inhibition (epsilon-aminocaproic acid-EACA) or alpha-adrenergic stimulation (norepinephrine) were provided simultaneously. The mechanism whereby norepinephrine initiated glomerular capillary thrombosis was not related to interference with fibrinolysis nor to potentiation of platelet aggregation and blood coagulation, as indicated by similar consumption of plasminogen and platelets in animals given thrombin alone or combined with norepinephrine, and by the lack of correlation between fibrinogen consumption and the incidence and severity of glomerular thrombosis produced with various dosages (1 to 3 mu/kg/min) of norepinephrine. With norepinephrine, microthrombi were also observed in the adrenals, the spleen and the gastric mucosa. Aspirin prevented the phenomena in the latter two organs, but was inactive or aggravating on thrombogenesis elsewhere. ADP associated with thrombin failed to trigger formation of microthrombi but initiated platelet-rich thrombi in the pulmonary vasculature when associated with norepinephrine. We conclude that unlike thrombin, ADP cannot be held responsible for the microthrombi elicited during experimental intravascular coagulation. Furthermore, the ability of norepinephrine to elicit glomerular thrombosis in thrombin injected rabbits may provide an explanation for requirement of alpha-adrenergic stimulation in the endotoxin-induced generalized Shwartzman reaction.
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PMID:Vasoactive agents and production of thrombosis during intravascular coagulation 1--comparative effects of norepinephrine in thrombin and adenosine diphosphate (ADP) treated rabbits. 652 6


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