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)

10 postmenopausal patients with hot flushes were given ethinyl estradiol, 20 mg daily, 3 weeks out of 4, for 16 weeks. Peripheral venous samples for coagulation factors 2, 7, 10, 7 + 10 complex and the coagulation inhibitor anti-thrombin 3 were taken twice before treatment; in the 6th, 10th, and 14th week of treatment, and 6-8 weeks after treatment stopped. There was a significant increase in mean values of coagulation factors 7, 10, and 7 + 10 complex in the 10 patients taking ethinyl estradiol. Factors 10 and 7 + 10 complex reached a peak after 6 weeks of treatment and then declined while the mean value of factor 7 continued to rise to a maximum of 138 + or - 11% by the 10th week of treatment. Factor 10 was the only factor significantly raised at the end of 14 weeks treatment. There was no significant change in factor 2 and anti-thrombin 3 in the patients on the ethinyl estradiol. These effects on coagulation factors during ethinyl estradiol therapy are, in general, similar to those found during treatment with conjugated equine estrogens and estradiol valerate in a previous study from the same laboratory. It appears that equipotent doses of ethinyl estradiol and "natural" estrogens have similar effects on these coagulation factors.
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PMID:Changes in coagulation factors in postmenopausal women on ethinyl oestradiol. 46

Estrogen-containing compounds are thrombogenic in man. The extent of thrombosis is dose-related, but a measure of this thrombogenicity is not currently available. Evidence is presented, using an animal model of venous thrombosis, that impaired Xa inhibitory activity (the rate of reaction between Xa and antithrombin III) correlates with the development of thrombosis initiated by thrombin in rabbits receiving an oral contraceptive compound. The responses in the clotting assay and in the extent of thrombosis are dose-related. The hypercoagulable state induced by oral contraceptives can be completely reversed by trace amounts of heparin.
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PMID:The activated factor X-antithrombin III reaction rate: a measure of the increased thrombotic tendency induced by estrogen-containing oral contraceptives in rabbits. 64 Apr 89

The effect of combined, low-dose oral contraceptives on blood coagulation factors was studied in 60 healthy women. 20 women received .5 mg/day norethindrone plus .06 mg ethinyl estradiol on alternate days of the cycle from Days 5 through 25, another group of 20 received an IUD, and a 3rd group of 20 received .5 mg/day norethindrone plus .045 mg ethinyl estradiol on alternate days of the cycle from Days 5 through 25. Blood samples were taken before and after 3 months of treatment. No clinically significant (P greater than .05) effect of either treatment regimen on such blood coagulation factors as platelet count, platelet adhesiveness, prothrombin time, thrombin time, fibrinogen, Factor 2 assay, Factors 5, 7, 8, 9, and 10, and fibrin/fibrinogen degradation products could be established. Both fresh and frozen blood samples were used in the study.
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PMID:Progestational agents and blood coagulation. VIII. Effect of low-dose, alternate-day, estrogen-progestin combinations on blood coagulation factors in man, with a special note on the effect of freezing of blood samples. 85 75

Oral contraceptives influence plasma proteins, causing changes in plasma procoagulants and fibrinolytic effectors. Estrogen is thought to be responsible for these changes, whereas progestogens, in particular those with an androgenic effect, may influence the magnitude of the changes. This concept is consistent with epidemiologic studies, suggesting a correlation between estrogen dose and cardiovascular episodes in oral contraceptive users. A delayed resolution of fibrin might contribute to an increased risk caused by decreased coagulation inhibition or fibrinolytic efficacy. Estrogen (30 micrograms or more) has a dose-dependent effect on clotting factors, including antithrombin III and proteins C and S. The effect of high- and low-dose oral contraceptives containing various progestogens on the fibrinolytic system is less clear. We have found that low-dose oral contraceptives containing levonorgestrel or lynestrenol enhance fibrinolysis, as revealed by an increase in plasminogen (30% to 40%), a decrease in histidine-rich glycoprotein (15% to 26%), an increase in tissue plasminogen activator activity (greater than 150%), and a decrease in tissue plasminogen activator inhibition (30% to 40%), concomitant with a slight decrease in tissue plasminogen activator antigen level (15% to 20%). New oral contraceptives contain less androgenic progestogens. Preliminary results of an ongoing study of women receiving either 20 micrograms of ethinyl estradiol with 150 micrograms of desogestrel or 30 micrograms of ethinyl estradiol plus 75 micrograms of gestodene revealed no change or changes similar to the older low-dose preparations after 6 months of treatment. Of particular importance was the finding that coagulation activation, expressed by the levels of thrombin-antithrombin III-complexes, fibrin formation, and the efficacy of fibrinolysis, expressed by the levels of fibrin degradation products, was identical in the two groups.
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PMID:Effects of newer oral contraceptives on the inhibition of coagulation and fibrinolysis in relation to dosage and type of steroid. 219 12

Epidemiologic studies have suggested a relationship between the use of oral contraceptives and mortality from cardiovascular diseases in older women. Therefore we studied generation and resolution of fibrin in 28 healthy women above age 30 years, using oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol. Thirty healthy nonusers served as control subjects. The oral contraceptive group had increased plasma concentration of thrombin-antithrombin III complexes (p less than 0.01), which indicated an enhanced generation of thrombin, increased plasma activity of tissue-type plasminogen activator (p less than 0.01), decreased plasma activity of plasminogen activator inhibition (p less than 0.01), and increased plasma concentration of fibrin degradation products (p less than 0.04). Interestingly, the ratio of thrombin-antithrombin III complexes/fibrin degradation products did not deviate significantly between groups. Twelve of the 28 women using oral contraceptives were light smokers, that is, less than 15 cigarettes per day. There were no differences in the determined variables between smokers and nonsmokers. Our study suggests that healthy women older than 30 years who use oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol have an enhanced generation and resolution of fibrin, while the hemostatic balance is unaltered. These findings are unaffected by moderate cigarette smoking.
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PMID:Enhanced generation and resolution of fibrin in women above the age of 30 years using oral contraceptives low in estrogen. 237 37

Inhibitors of the coagulation system were measured in 71 women taking 4 oral contraceptives for 1-8 years, 2 combined pills, Bisecurin and Ovidon, a low-dose combined pill, Rigevidon, and a biphasic, Anteovin. The article begins with a review of the clinical significance and recent research on serine protease inhibitors. The pill formulations were: Bisecurin, 50 mcg, ethinyl estradiol and 1 mg ethinodiol diacetate; Ovidon, 50 mcg, ethinyl estradiol and 250 mcg, d-norgestrel; Rigevidon, 30 mcg ethinyl estradiol and 150 mcg, d-norgestrel; Antiovin 50 mcg, ethinyl estradiol and 50 mcg, d-norgestrel for 11 days and with 125 mcg d-norgestrel for 10 days. Thromboelastographic values r and I, indicating hypercoagulation, were significantly higher for pill users compared to 28 controls. No change was seen in prothrombin time (PT), and partial prothrombin time (PTT), fibrinogen values or ethanol gelation. Antithrombin III biological activity and quantity assayed immunologically decreased as much as 20%. The fixed dose pills significantly enhanced alpha 1-antitrypsin, a possible biochemical risk factor for thromboembolic disease. Alpha 2-macroglobulin levels did not change. The results showed that the increased coagulability and enhanced incidence of thromboembolic disorders associated with oral contraception may be caused by a decrease in thrombin inhibitors as well as increased alpha 1 antitrypsin, which inhibits the fibrinolytic system.
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PMID:Action of hormonal contraceptives on the coagulation system and some of its inhibitors. 243 39

We investigated whether changes in plasma oxidative properties could occur after oral (hormonal) contraceptive (OC) administration in female rats and whether such changes could be responsible for the platelet increase in aggregation and lipid biosynthesis observed with that treatment. Platelets and plasma (platelet-poor) from control and OC (ethinyl estradiol + lynestrenol)-treated rats were prepared separately. Thrombin-induced aggregation of control platelets was markedly enhanced after incubation for 4 (p less than 0.025) to 60 (p less than 0.001) minutes in OC as compared with control plasma. Under the same conditions, platelet lipid biosynthesis was increased also (p less than 0.05 to p less than 0.01), but after 3 hours incubation. The enhanced response of platelets to aggregation induced by OC plasma could be inhibited by adding either glutathione (p less than 0.025), vitamin E (p less than 0.025), catalase (p less than 0.05), or peroxidase + glutathione (p less than 0.005) to plasma or 2,6,di-bis(ter-butyl)p-cresol (p less than 0.05) to platelets before incubation. The peroxidized free fatty acids isolated from OC plasma added to normal platelets induced a 150% (p less than 0.001) increase in the response to thrombin as compared with the fatty acids from control plasma. In addition, the level of malondialdehyde and conjugated dienes was significantly (p less than 0.02 to p less than 0.001) increased in OC compared with control plasma. We conclude that the enhanced formation in plasma of lipid hydroperoxides seems to be the initial event stimulating platelets after OC treatment, at least in rats.
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PMID:Hormonal contraceptive increases plasma lipid peroxides in female rats. Relationship to platelet aggregation and lipid biosynthesis. 253 71

A relationship between use of oral contraceptives and thromboembolic disease has been suspected for years. Recent experimental studies indicate that venous thromboses can be triggered by the interaction of stasis and coagulation activation, also called hypercoagulability. Stasis is promoted by widening of the veins, a change known from pregnancy, although it is not clear whether this can be definitively related to estrogen or progestagen release. In addition, estrogens cause an increase in fibrinogen neosynthesis and increased whole blood viscosity. At low flow rates this causes early occurrence of erythrocyte aggregates. Although an increase in coagulation factors observed by many authors among oral contraceptive users cannot be unequivocally equated to an increased thromboembolic risk, detection of activated coagulation factors is a sensitive indicator of coagulation activation. Thus it was shown by the level of circulating fibrin in plasma that varied coagulation activation occurred in users of 30 and 50 micrograms ethinyl estradiol. In this study of a 3 stage contraceptive (0.5 mg norethisterone, 0.035 mg ethinyl estradiol; 0.75 mg norethisterone, 0.035 mg ethinyl estradiol; 1 mg norethisterone, 0.35 mg ethinyl estradiol) with 22 patients, no significant change in fibrinogen level was found. The same applied to other hypercoagulability parameters fibrinopeptide A and antithrombin III. The constant blood level of early fibrinolysis product F-CB3 also indicated absence of relevant thrombin induced coagulation activation. This is apparently linked to low estrogen dose.
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PMID:[Changes in blood coagulation during hormonal contraception]. 409 18

Antithrombin III was determined by the van Kaulla method in 19 women taking combined oral contraceptives containing 75-150 mcg estrogen, 60 women taking pills containing 50 mcg ethinyl estradiol and .5 mg norgestrel, and in 79 controls. Subjects were aged 20-45, had been taking pills from 3 months to 5 years, and were sampled on Day 23 of the menstrual cycle. The antithrombin assay measured, by fibrometer, neutralization of a given amount of thrombin in the presence of fibrinogen, by serum stored frozen in plastic tubes: controls with Michaelis buffer took 7 seconds. The women on 75-150 mcg estrogen pills had mean antithrombin values of 33 seconds with 12 (63%) blow normal limits (30 seconds). This was signifigantly lower than the values for the controls. (p.001) Those on 50 mcg ethinyl estradiol averaged 60 seconds, with 7 (12%) abnormal. The controls' mean antithrombin values were 79 seconds, with 4 (5%) abnormal.
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PMID:[Antithrombin 3 changes in women using oral contraceptives]. 459 16

The effect of Norplant, a subdermal contraceptive implant containing levonorgestrel, on blood coagulation factors was investigated in 47 healthy women. Coagulation parameters were also measured in 55 subjects who were taking combination type oral contraceptives (OCs) (either a pill containing 1 mg norethisterone and 50 mcg mestranol or a preparation containing 150 mcg levonorgestrel and 30 mcg ethinyl estradiol). Blood sampling was carried out at admission and after 1, 3, and 6 months of contraceptive use. Parameters measured included platelet count, prothrombin time, thrombin time, partial thromboplastin time with kaolin, clotting factors I, II, V, and VI-XIII, plasminogen, antithrombin III, alpha 1 antitrypsin, alpha 2 macroglobulin, and fibrinogen degradation products. Norplant users showed a lack of effect on the factors tested, except for factor VII activity, which was increased, and antithrombin III concentration, which was decreased after 3 months of use. In contrast, the combined OC users evidenced marked changes in platelet count, the screening tests, and most coagulation promoting factors. These changes became more pronounced after 6 months. Women taking the levonorgestrel-ethinyl estradiol OC evidenced less pronounced changes in some coagulation parameters than those taking the norethisterone-mestranol preparation; however, the high dropout rate among OC users limits the conclusions that can be drawn from these results. These results point to a relative lack of effect of Norplant implants on the blood coagulation-fibrinolytic system, presumably due to the absence of estrogen and the low dose of progestogen delivered to the body.
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PMID:Effect of levonorgestrel contraceptive implants, Norplant, on blood coagulation. 644 Jul 38


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