Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Protamine-sulfate blocked non-enzymatic fibrinolysis not only in vitro but also in vivo through binding of heparin and dissociation of its complexes, which are of great importance as humoral components of the anticoagulation system. Almost complete blocking of humoral agents of the anticoagulation system, caused either by a single intravenous administration of protamine-sulfate at large doses or by repeated administration of the substance at moderate doses within 14 days, led to death of the animals as a result of thrombotic complications related to appearance of additional thrombin in blood circulation. In these cases thrombosis occurred into coronary blood vessels. The non-enzymatic fibrinolytic effect was not observed in extracts from lungs, auricula atrii and liver tissue of experimental animals, treated with protamine-sulfate, as compared with the controls, administered with physiologic solution.
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PMID:[Thrombotic complications in the blocking effect of protamine sulfate on nonenzymatic fibrinolysis in the blood of animals during activation of the anticoagulation system]. 44 92

Heparin activity was assessed in 11 patients who underwent extracorporeal circulation for open-heart surgery. The activated partial thromboplastin time (A-PTT), thrombin time, protamine sulphate titration and factor Xa inhibition assay were used. The patients received heparin 3 mg/kg body weight, and 20 mg/450 ml blood was added to the pump. When the operative procedure was extended beyond 100 minutes patients received an additional 1,5 mg heparin/kg body weight. Protamine sulphate in a dose of 1,5 mg/1 mg heparin, was given to neutralize the heparin activity. The A-PTT was the easiest test which gave reliable results. The factor Xa inhibition assay measured heparin levels most precisely and mirrored the A-PTT results in all but one instance. These results indicate that the protocol employed produced adequate anticoagulation for the bypass procedure in all the patients. Protamine sulphate failed to neutralize heparin adequately after bypass in the 3 patients who received additional heparin during the surgical procedure. The monitoring of heparin activity during and after extracorporeal circulation is a desirable addition to open-heart surgical treatment.
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PMID:The monitoring of heparin activity during extracorporeal circulation. 88 33

The functional operation of the cell surface pro-u-PA and plasminogen activating system has previously been shown to depend on the assembly of u-PA receptors, plasminogen binding sites, and their respective ligands at the focal adhesions of cell extensions. We now show that additional factors operate that affect the persistence of functional activity and that evidently involve charge interactions mediated by polyanions, such as those found in the cell surface proteoglycans. Heparin-like compounds and protamine were identified as fast-acting stimulators of cell surface plasminogen activation. Heparin stabilized surface u-PA activity during plasminogen activation, and we propose that a heparin binding site exists in the kringle structure of u-PA. Heparin at 40 micrograms/ml could reduce u-PA loss to only 20% compared with 60% on control cells activating plasminogen. Protamine (25 micrograms/ml) exerted a strong stimulatory effect on the level of generated bound plasmin and notably prolonged the persistence of this activity, so that 100 minutes after addition of plasminogen the level of plasmin on protamine-treated cells was five times higher than on control-treated cells. The effect of protamine on plasmin clearance suggests that an unknown plasmin inhibitor may be produced by rhabdomyosarcoma cells, whose action is accelerated by endogenous polyanions, in an analogous manner to thrombin inactivation by antithrombin III and protease nexin on endothelial cells and fibroblasts, respectively. The stimulatory effects of heparin and protamine do not affect the inactivation of cell surface u-PA by recombinant PAI-2.
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PMID:Stimulation of cell surface plasminogen activation by heparin and related polyionic substances. 183 80

The anticoagulant, lipolytic and protamine reversible effects of high doses of low molecular weight (LMW) heparin 21-23 and unfractionated heparin were compared in man. 7,500 units of each heparin were applied, which corresponds to 90 mg LMW heparin and 48 mg unfractionated heparin. The anticoagulant properties of the LMW heparin are characterized by a doubled half life of factor Xa activity, smaller influence on aPTT and thrombin after intravenous (i.v.) and subcutaneous (s.c.) injection, and higher bioavailability of factor Xa activity after s.c. administration (90% versus 15%). Protamine chloride completely neutralizes the effect on aPTT and thrombin and reduces the anti factor Xa activity by 60%. The bleeding time is prolonged by both normal and LMW heparin by 20%. This effect is normalized by protamine chloride, too. Thrombelastography with recalcified whole blood demonstrates that protamine chloride shortens but not completely normalizes the coagulation time in presence of either unfractionated or LMW heparin. The half life of lipoprotein lipase (LPL) activity is 60 min after i.v. administration of unfractionated heparin and 120 min with LMW heparin. Although the release of lipases (LPL and HTGL) is higher after i.v. and s.c. administration of the LMW heparin they do not induce higher releases of free fatty acids. This indicates that the lipolytic activity of this LMW heparin and unfractionated heparin is similar. The results show an improved anticoagulant pharmacological profile of this LMW heparin as compared to unfractionated heparin. Protamine normalizes the anticoagulant effects of LMW heparin with exception of a residual anti factor Xa activity and normalizes the changes of bleeding time and thrombelastography.
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PMID:The pharmacological profile of the low molecular weight heparin 21-23 in man: anticoagulant, lipolytic and protamine reversible effects. 248 15

Protamine sulphate-induced aggregation of soluble fibrin causes an increase of turbidity in the plasma sample, which can be measured by means of kinetic turbidimetry. A method was developed which is sufficiently sensitive for the determination of soluble fibrin in plasma without interfering with the sensitivity for fibrinogen. The performance of the assay was studied by analysing plasma samples with high concentrations of fibrinogen and soluble fibrin at different pH values, at different concentrations of plasma and protamine sulphate, and using different wavelengths and analysis times. Measurement of thrombin-induced fibrinogen-fibrin-transformation by the developed turbidimetric method, gave results that correlated well with the release of fibrinopeptide A. The new protamine sulphate method for turbidimetric determination of soluble fibrin is characterized by its practicability, rapid availability of reproducible, quantitative results, and its economy of reagents and time in single and serial analysis. Therefore it seems well-suited for the routine diagnosis of hypercoagulability with increased fibrinogen turnover.
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PMID:Determination of soluble fibrin by turbidimetry of its protamine sulphate-induced paracoagulation. 274 64

The heparin neutralizing properties of protamine chloride on conventional heparin (porcine mucosa) and on low molecular weight heparin (Kabi 2165) were studied in vitro. Protamine chloride neutralized 99% of the delaying effect of conventional heparin on the activated partial thromboplastin time, whereas only 70% of the effect of low molecular weight heparin was neutralized. The neutralizing effect of protamine chloride on the inhibition of factor Xa (clot test) was 95% for conventional heparin and 55% for low molecular weight heparin, whereas the effect of both heparin preparations on the thrombin inhibition could be completely neutralized. We conclude that conventional heparin is neutralized more effectively in vitro by protamine chloride than is the low molecular weight heparin. The findings do not exclude that protamine chloride is able to suppress in vivo bleedings caused by low molecular weight heparin.
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PMID:Does protamine chloride neutralize low molecular weight heparin sufficiently? 285 82

The adverse effects of protamine sulfate, used to neutralize the anticoagulant action of heparin, include systemic hypotension, pulmonary artery hypertension, thrombocytopenia and leukopenia. For further evaluation of protamine's mechanism of action, a three-part investigation was performed. In part I platelet-rich plasma (PRP) was prepared from canine blood samples (n = 6) taken before and 2 minutes after injection of protamine. In part II human PRP (n = 5) was preincubated with protamine or distilled water. Adenosine diphosphate-induced aggregation of protamine-treated platelets was unchanged, but thrombin-induced aggregation was inhibited in both canine and human preparations (p less than 0.05). In part III thrombocytopenia was produced in splenectomized dogs (n = 5), using microporous filters, to 4.5-8.4% of the initial platelet count. Protamine reversal of the heparinization caused hypotension (maximally -29 mmHg 90 s after protamine), but not pulmonary arterial hypertension. Leukopenia developed before additional thrombocytopenia appeared. Protamine-platelet interaction inhibits thrombin-induced platelet aggregation. Platelets may play an important role in the pulmonary pressure rise during protamine reversal, but do not mediate the systemic hypotension.
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PMID:The effect of protamine sulfate on platelet function. 338 50

In spite of its unpredictable kinetics, heparin is still not generally monitored during peripheral vascular surgery. To evaluate heparin levels and neutralisation, plasma heparin concentrations were measured using a chromogenic substate method during 20 consecutive operations on the Abdominal Aorta. This was combined with measuring activated partial thromboplastin time (APTT), thrombin time (ThT), prothrombin time (PT), antithrombin-III (AT-III) and fibrinogen concentration. Heparin concentration 5 min after administration and the elimination rate showed a wide variation. Using a standard dosage for all patients resulted in plasma heparin levels that are potentially too low in some patients. The APTT and ThT were found to be unsuitable for an exact calculation of heparin levels. Protamine administration based on the surgeon's judgement of haemostasis was inadequate. Furthermore an intraoperative decrease of AT-III and fibrinogen was seen in eight patients. It is advisable and possible to have direct monitoring of heparin concentration during peripheral vascular surgery.
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PMID:Monitoring heparin and haemostasis during reconstruction of the abdominal aorta. 350 34

Non-heparinized and covalently-heparinized PTFE grafts, sheep aorta, carotid artery and jugular vein were evaluated according to their ability to adsorb and inactivate thrombin. All surfaces, except non-heparinized PTFE caused considerable losses of enzymatically active thrombin from the solution. Covalently-heparinized PTFE and jugular veins adsorbed thrombin, which was inactivated on subsequent contact with antithrombin III. Despite the same loss from the solution as was encountered with veins arteries adsorbed significantly smaller amounts of thrombin. Protamine treatment of covalently-heparinized PTFE almost totally abolished the ability to adsorb thrombin. It is concluded that 1) arteries possess a stronger thrombin inhibitory capacity than veins, possible explanations to this being a different glucosaminoglycan or the presence of antithrombin III in the arterial wall and 2) that heparinizing PTFE results in a pronounced ability to inactivate thrombin.
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PMID:Thrombin uptake and inhibition on heparinized polytetrafluoroethylene (PTFE) grafts and native sheep vessels. 371 19

Human umbilical vein grafts were treated with either conventional or LMW heparin, followed by exposure to alcohol. The grafts were investigated for their ability to adsorb and inactivate thrombin, and comparison was made with non-heparinized and saline-alcohol treated grafts and grafts supplied with a covalently bonded layer of conventional heparin. In addition, the effect of protamine exposure to heparin-alcohol and LMW heparin-alcohol treated grafts as well as native human umbilical veins (HUV) was studied. Native HUV and heparin treated graft surfaces adsorbed and inactivated thrombin, whereas non-heparinized and saline-alcohol treated grafts inactivated surface-bound thrombin to only a small degree. Surface-bound LMW heparin exhibited a significantly lower ability to inactivate thrombin as compared with conventional heparin, but LMW heparin-alcohol surfaces were better than non-heparinized ones. Protamine treatment of "heparinized" surfaces impaired the thrombin inhibiting ability of the heparin-alcohol surface, whereas this property was totally abolished for the LMW heparin-alcohol surface. The findings indicate that LMW heparin, despite its weaker thrombin inhibiting capacity, may be an alternative to conventional heparin, for "heparinizing" the human umbilical vein graft. Protamine exposure may be potentially harmful for a heparin treated surface, although protamine concentrations used in the present in vitro study may not be reached in vivo. The native HUV was not at all affected by protamine exposure regarding its ability to inactivate thrombin.
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PMID:In vitro evaluation of a biologic graft surface. Effect of treatment with conventional and low molecular weight (LMW) heparin. 650 22


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