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:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By devising and applying quantitative methods for the assay of thrombin and autoprothrombin C and by developing techniques for their purification, it was possible to obtain information about the function and properties of antithrombin. The inhibitor is a protein for which the initial purification steps consist of removing fibrinogen from plasma by heating to 56 degrees for 3 min, removing prothrombin complex by absorption on barium carbonate, absorbing the antithrombin on aluminum hydroxide, and eluting with phosphate buffer. Antithrombin is limited in its capacity to neutralize thrombin activity, and, under some conditions, the rate of inhibition was accelerated, but equivocal results were involved. Heparin cofactor was found to be essential for retarding the formation of thrombin, and, by inference, it is essential for retarding the formation of autoprothrombin C. Heparin cofactor and antithrombin III are the same. Thrombin absorbs on fibrin, and this has been referred to as the "antithrombin I effect." Interference with the thrombin-fibrinogen reaction by mixtures of antithrombin III and heparin is called the "antithrombin II henomenon." The acceleration of thrombin inactivation at the time thrombin forms is called the "antithrombin IV effect." It was discovered that antithrombin III neutralizes thrombin, as well as autoprothrombin C. The inhibitor and the enzyme form a mutual depletion system. To assay for antithrombin III, a standard quantity of thrombin (about 1,100U/ml) was reacted with antithrombin III for 2 hr. The percent thrombin inactivated was then measured. In random samples of human blood, a wide range of antithrombin III concentration was found. The inhibitor is relatively stable in plasma and serum. It is not changed in concentration when Dicumarol therapy is instituted. Ether extraction of plasma reduces antithrombin III activity. Seitz filtration of plasma did not remove activity. Under special conditions, antithrombin III enhances esterase activity of thrombin. Under special conditions, thrombin regenerates from the thrombin-antithrombin III complex. Antithrombin III neutralizes the activity of prethrombin-E and thrombin-E; consequently, an active histidine center found in the B1 chain of thrombin is not essential for the binding of antithrombin. Autoprothrombin II-A activity was neutralized by antithrombin III. Autoprothrombin C was found to be neutralized by antithrombin III; the amounts required varied with the molecular forms of autoprothrombin C. Thrombin and autoprothrombin C apparently occupy the same binding sites on antithrombin III. An equation was developed to account for all the known characteristics of antithrombin III functions. The kinetic aspects of thrombin neutralization were found to correspond exactly with those of autoprothrombin C. Antithrombin III is a high-capacity inhibitor of the two most powerful enzymes in blood coagulation.
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PMID:Antithrombin III: a backward glance o'er travel'd roads. 4 4

Anticoagulation has been reported to ameliorate antiglomerular basement membrane glomerulonephritis (anti-GBM-GN) while its effect on chronic immune complex glomerulonephritis (IC-GN) as studied in the NZB mouse is unclear. Chronic serum sickness IC-GN was induced in rabbits by injecting bovine serum albumin (BSA) daily. Anti-GBM-GN was induced by i.v. injection of a known amount of heterologous anti-GBM antibody. Heparin was administered beginning at two to six weeks after the first BSA injections or before the administration of anti-GBM antibody, on various schedules from 5000 U every 12 hr to 8000 U every 8 hr. With this dosage the partial thromboplastin time remained greater than 1-1/2 to 2-1/2 times the control at the time of the subsequent heparin injection. Heparinized and nonheparinized groups were matched according to duration of disease, maximum anti-BSA concentrations or anti-GBM antibody dosage--and no significant differences were found in proteinuria; severity of the glomerular histologic lesions; or immunofluorescence patterns of immunoglobulin G (IgG), third component of complement (C3), BSA or fibrinogen-related antigen(s) (FRA). Crescent formation was not prevented. This study shows that heparin in the maximum permissible dosage is ineffective in preventing glomerular FRA deposition or altering the progression of experimental IC-GN or anti-GBM-GN in rabbits.
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PMID:Failure of heparin to affect two types of experimental glomerulonephritis in rabbits. 12 30

Inhibitory activities of alpha2-plasmin inhibitor against various proteases were investigated. The inhibitor promptly inhibited the esterolytic activity of alpha-chymotrypsin and progressively inhibited the esterolytic or amidolytic activities of bovine plasma kallikrein, bovine thrombin and bovine activated factor X. Heparin had no effect on the reaction of the inhibitor with thrombin or activated factor X. However, the inhibitor had no effect on the activities of human C-1-esterase, papain and snake venom kininogenase. On the basis of its rapid inhibition of kallikrein, alpha2-plasmin inhibitor is considered to exert some regulating effect on kallikrein activity in plasma.
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PMID:Inhibition of proteases in coagulation, kinin-forming and complement systems by alpha2-plasmin inhibitor. 14 28

Antithrombin III is one of the main inhibitors in the blood coagulation mechanisms. Thrombin and factor Xa are slowly inactivated by it, as well as other serine proteinases of the coagulation mechanisms. Heparin tremendously accelerates the inhibitory function of antithrombin III. In the process antithrombin III activity is also reduced. Heparin retards the thrombin-fibrinogen reaction, but otherwise the effectiveness of heparin as an anticoagulant depends on antithrombin III in laboratory experiments, as well as in therapeutics. The activation of prothrombin is inhibited, and any thrombin or other vulnerable protease that might generate becomes inactivated. The measurement of antithrombin III concentration in blood is now achieved by research methods, as well as by methods that are practical for routine use. The tests require either thrombin or factor Xa as substrate, and could be specific for antithrombin III. There are congenital as well as acquired deficiencies of antithrombin III. The inhibitor is also found in tissues.
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PMID:Antithrombin III. Theory and clinical applications. H. P. Smith Memorial Lecture. 34 19

Five commercially available activated partial thromboplastin time (APTT) test systems were compared with the kaolin partial thromboplastin time (KPTT) method to determine sensitivity in detecting minor coagulation defects. All reagent systems detected severe factor VIII-, IX-, and XI-deficient hemophilia. Homozygous states of factor XII deficiency, Fletcher factor deficiency, and high-molecular-weight kininogen deficiency (Fitzgerald trait) also showed abnormally long APTTs by all systems. Of 19 samples from patients with deficiencies of factors XII, VIII, IX, XI, and II ranging from 2.5 to 52%, eight had deficiencies that were not detected by reagent A (ellagic acid); two, by reagent B (ellagic acid); two, by reagent C (kaolin); one, by reagent D (silica); one, by the KPTT method. All deficiencies were detected by reagent E (celite). Heparin effect on plasma was less well detected by reagent A (ellagic acid) than with the other test systems. APTT test systems can vary greatly in their abilities to detect minor coagulation abnormalities.
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PMID:Activated partial thromboplastin time and minor coagulopathies. 42 Jan 68

A heparinized high-strength elastomer has been developed which is potentially useful as a nonthrombogenic vascular prosthesis. A surface hydroxylated styrene-butadiene-styrene (SBS) block copolymer with at least 40% extent of reaction after glow-discharge cleaning was coated with a 20% acetylated polyvinyl alcohol/heparin mixture containing glutaraldehyde and magnesium chloride. After curing at 80 degrees C for 100 min, the polyvinyl alcohol, heparin, and hydroxylated SBS were covalently bound to each other by acetal bridges. The effects of the various substrate and coating parameters were optimized to achieve very strong adhesion between the coating layer and the surface hydroxylated SBS. Heparin was not leached from the surface of the new material using 3M saline at pH 7.4 despite a detection limit of 10(-5) micrograms heparin/cm2 min. Prolonged partial thromboplastin times of greater than 1200 sec were observed (control: PTT = 120 sec). Preliminary ex vivo testing using a simple arteriovenous shunt in the leg of a rabbit showed good thromboresistance. The heparinized SBS shunt chamber remained patent for more than two hours without desorption of heparin. It was concluded that surface hydroxylated SBS heparinized by acetal coupling owed its thromboresistance to the heparin covalently bound to the surface and not to a microenvironment of heparin in solution at the blood/material interface.
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PMID:Heparinized styrene-butadiene-styrene elastomers. 43 24

The physician frequently encounters the problems of deep vein thrombosis and pulmonary embolism. Recently, a number of studies have been published which are of considerable help in the management of these disorders. It has been shown that in many cases, low-dose heparin is effective in the prevention of both venous thrombosis and pulmonary embolism. However, once venous thrombosis has already occurred, it is necessary to use full-dose heparin, preferably by the continuous intravenous route, with maintenance of the partial thromboplastin time (PTT) at 1 1/2 times the control at all times. Although monitoring the PTT may not prevent hemorrhage, it will help prevent further thrombosis. Heparin is generally continued for seven to ten days. During this time warfarin is generally begun, and it is important to continue the patient on warfarin for five to seven days while the patient is receiving intravenous heparin therapy. After stopping heparin, oral anticoagulation with warfarin should be continued for six weeks. Then, in the absence of a previous history of venous thromboembolism or a known predisposing condition, it is safe to abruptly discontinue anticoagulation in most patients.
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PMID:Heparin and warfarin: use of anticoagulants in the prevention and treatment of venous thrombosis and pulmonary embolism. 43 53

The activated parial thromboplastin time is susceptible to changing concentrations of factor VII even in the presence of heparin. Heparin delays, but does not abolisn, thrombin generation, and this delay is obviated by factor VIII. It is not known if activated parial thromboplastin time shortened by increased factor VIII demands an increase in heparin administration.
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PMID:Heparin monitoring and thrombosis. 44 97

In 12 mongrel dogs, the comparative effectiveness of systemic versus regional heparinization was studied after injecting 100 units per kilogram of heparin into a systemic vein or regionally into an artery. Activated plasma thromboplastin time was used to monitor the heparin activity, and the coagulability of blood in the general circulation was compared with the coagulability of blood in the excluded circulation distal to the vascular clamps. Both methods of heparinization were found to be equally effective. Heparin injected regionally rapidly achieves a uniform distribution in the excluded, as well as the general, circulation and, as such, cannot be called regional. There was no difference in coagulability of blood in the general circulation compared with the blood in the excluded circulation. Results of this study suggest that regional heparinization is, in fact, systemic heparinization.
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PMID:Regional versus systemic heparinization. 45 13

Two methods of calculating heparin infusion rates for patients with venous thrombotic disease were compared; one method was based on a one-compartment pharmacokinetic model, the other on patient weight. Sixty-eight patients with presumed thromboembolic disease were started on continuous i.v. heparin sodium (porcine) using an infusion pump. Patients were divided into two groups--the infusion rate of Group I was based on patient weight (77 units/kg/4 hrs) and the infusion rate of Group 2 was determined by a pharmacokinetic equation based on a one-compartment heparin model. Heparin effect was measured by an activated partial thromboplastin time (APTT). The initial heparin infusion rate for Group 1 (4,784 +/- 672 units/4 hrs) was significantly greater (p less than 0.039, two-sample t-test) than that for Group 2 (4,413 +/- 779 units/4 hrs), but the variances of the rates were not significantly different (p = 0.40, ratio of variance F-test). Both methods for estimating initial heparin infusion rates gave mean APTT values in the center of the therapeutic range, but the variance in the APTTs of Group 2 patients was significantly smaller (p = 0.004) than that of Group 1. The pharmacokinetic model was more precise and reliable. This model should be valuable for insuring heparin's therapeutic effect without exposing patients to the potential risk of hemorrhage.
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PMID:Improved methods for estimating initial heparin infusion rates. 46 94


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