Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activated partial thromboplastin time (APTT) has been advocated for monitoring heparin effect. This study was designed to determine the in vitro sensitivity to heparin of commercially available APTT reagents. Heparin was added in increasing concentrations to pooled citrated plasma. Fibrometer APTT determinations were performed at each concentration using General Diagnostics, Ortho, Dade, Hyland, and BBL reagents. A tilt-tube kaolin-activated partial thromboplastin time was also tested using a Sigma partial thromboplastin prepared by the method of Bell and Alton. The General Diagnostics, Sigma, and Ortho reagents displayed linear heparin sensitivity; the General Diagnostics APTT was prolonged 1 1/2-2 1/2 times in a plasma heparin range that prolonged a modified in-vitro Lee-White clotting times 2-3 times. The other reagents were either insensitive, too sensitive, or nonlinear in heparin response. Thus, commercial reagents vary widely in their in-vitro sensitivity to heparin.
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PMID:Variation among commercial activated partial thromboplastin time reagents in response to heparin. 85 45

The effects of hormonal contraceptive agents on the vascular system were studied in rats, dogs, and 34 women taking oral or injectable steroid contraceptive agents. Changes in the surface charge characteristics of the blood vessel wall and blood cells were observed. In dogs, the reduction in pore surface charge was greater in veins than in arteries. In rats, the induced mesenteric occlusion times were significantly reduced (p less than .001). However, Provera did not significantly reduce induced occlusion time in these animals (p greater than .01). Ov ral and Demulen lowered the mobilities of erythrocytes and platelets in women. Plasma coagulation times were not markedly altered in women receiving injectable progestin. Acitivated partial thromboplastin times were slightly decreased by Ovral and Demulen. The results suggest an increased tendency toward thrombosis in women taking steroid hormone contraceptive agents.
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PMID:Hormonal steroids: effects on the vascular system. 121

Citrated samples from 100 patients on i.v. heparin and 20 normal patients were tested with three batches each of three activated partial thromboplastin time (APTT) reagents: Thrombosil I (Ortho); Automated APTT (Organon Teknika) and Actin FSL (Baxter). The ratio of APTT over the geometric mean normal APTT for each heparinized sample was calculated. One batch of reagent arbitrarily chosen as a reference gave the ratios APTRREF (y). The remaining reagents to be standardized against the reference system gave the ratios APTRTEST (x). The best correlation between systems was given by log vs log x. Standard curves were prepared from the APTT ratios of the 20 normal patients and 65 of the heparinized samples. On plotting log APTRTEST vs log APTRREF the y intercept was close to zero so x was expressed in terms of y using; log x = HSI. log y, where HSI (Heparin Sensitivity Index) = slope. The APTRTEST results of the remaining 35 heparinized samples were transformed using; APTRTRANS = (APTRTEST)HSI.APTRTRANS was then compared to APTRREF to determine whether the transformation brought the results closer to the reference. We conclude that although some improvement was found by using the transform, it was not possible to mathematically relate APTT results due to a high degree of variation between results using different reagents. A standard APTT reagent for the monitoring of heparin therapy is recommended. A separate APTT reagent may be required for the screening of factor deficiencies and lupus anticoagulants.
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PMID:An attempt to standardize APTT reagents used to monitor heparin therapy. 133 84

Researchers from Gainesville, Florida compared data on 20 women who were randomly assigned the triphasic oral contraceptive (OC) Triphasil (ethinyl estradiol and levonorgestrel) with data on 24 women who were randomly assigned the triphasic OC Ortho-Novum (ethinyl estradiol and norethindrone) and data on 8 women who were controls to evaluate these 2 triphasic OCs' effects on coagulation and anticoagulation factors. They measured these factors at baseline and 6 and 12 months after beginning OC use. Both OCs significantly reduced prothrombin time (Triphasil at 6 and 12 months, p.001; Ortho-Novum at 6 months, p01, and at 12 months, p.001). They also decreased partial thromboplastin time (Triphasil at 6 months, p.01), and at 12 months, p.001; Ortho-Novum at 6 months, p.01). Both OCs significantly increased Factor XII after 6 and 12 months (Triphasil p.001 and p.01 for controls and p.05 from baseline, respectively; Ortho Novum p.01). Ortho-Novum considerably increased fibrinogen antigen at 6 and 12 months (p.05 and p.001 from baseline and p.05 for controls, respectively) while Triphasil increased it only at 12 months (p.05). Platelet counts remained the same. Ortho-Novum markedly increased antithrombin III activity after 6 months (p.05). Even though neither OC changed antithrombin III antigen, they did significantly increase alpha-1-antitrypsin antigen and plasminogen antigen and activity at 6 and 12 months as well as alpha-2-antiplasmin antigen at 12 months. Ortho-Novum increased alpha-s-antiplasmin antigen at 12 months. No great differences in coagulation or anticoagulation factors existed between the OCs. The mean values were within reference ranges. These results showed that the OCs had the same, limited effects on hemostasis and changes in coagulation factors offset changes in anticoagulation factors.
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PMID:Changes in coagulation and anticoagulation in women taking low-dose triphasic oral contraceptives: a controlled comparative 12-month clinical trial. 144 74

Accurate prothrombin time tests are important because they are frequently performed on presurgical patients to evaluate their blood-clotting status. We studied the effect of temperature (27-47 degrees C) on PTs obtained with eight different brands of thromboplastin. We also compared the sensitivities of two types of coagulation timers to changes in blood viscosities between 1 and 16 mPa/s. Viscosities were measured with the Brookfield Digital Viscometer. The MLA Eletra 800 and the BBL fibrometer were used to measure PTs. All eight thromboplastins gave convex curves of PT versus temperature, with optimum values lying between 38 and 39 degrees C. The curves were fitted to 4th-degree polynomials which showed that a mean temperature bias of 2 degrees C can increase PTs. Ortho Brain (7.8% change) was affected the most, while thromboplastin C (4.4% change) was affected the least. Plots of PT versus viscosity showed that the BBL fibrometer, which uses an electromechanical sensor, was more affected by viscosity than the MLA Electra 800, with an optical detector. However, above 8.2 mPa/s, all PTs were significantly elevated. Hence, patients with macroglobulinemia, whose plasma viscosities sometimes exceed 8.2 mPa/s, may have falsely elevated PTs. We conclude that temperature and viscosity are critical factors in the test and significantly contribute to within and between laboratory variations in PT measurements.
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PMID:Effects of temperature and viscosity on prothrombin times of blood. 191 74

Thirty-six young, healthy, nonsmoking women have been selected to check the effect of low-dose oral contraceptives on hemostasis. Two identical groups were treated by Marvelon (a monophasic oral contraceptive containing ethinyl estradiol and desogestrel) or Trigynon (a triphasic oral contraceptive containing ethinyl estradiol and levonorgestrel) for a 6-month period. In the absence, previously controlled, of substantial differences between the effects of each treatment on hemostasis, all the results were pooled at the third and sixth month of the study. The effects of oral contraceptive treatment were as follows: (1) platelet number, platelet aggregating ratio, and plasma beta-thromboglobulin level were not significantly altered, and (2) antithrombin III activity was not reduced despite a slight decrease or antigen concentration. The von Willebrand factor parameters, factor VIII:C, factor VII:C, and clottable fibrinogen were significantly increased. Plasminogen (activity and antigen concentrates) and alpha 2-antiplasmin levels were also significantly increased. Activated partial thromboplastin time and euglobulin lysis time measured after venous occlusion were significantly shortened. Although statistical analysis did not show dramatic changes in all these parameters, some individual extreme values were substantially altered. Therefore we believe that these later values are worthy of cautious consideration for weighing the role that hemostasis factors might play in individual thrombotic risk.
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PMID:Hemostasis profile in women taking low-dose oral contraceptives. 214 79

Two automatic coagulometers, ACL 810 (Instrumentation Laboratory), a laser-nephelometric centrifugal analyzer, and KoaguLab 40 A (Ortho Diagnostics), an optical automatic coagulometer, were compared with the manual tilt-tube method for the performance of activated partial thromboplastin time (APTT). Seven commercial APTT reagents were used for duplicate determinations in 30 normal controls, 26 patients with liver disease, and 33 patients on full-dose heparin treatment. Clotting times were longer with the manual method than with ACL 810 and, to a lesser extent, with KoaguLab 40 A. Average imprecision of duplicate determinations (coefficient of variation [CV]) was less with ACL 810 (less than 1.5%) than with KoaguLab 40 A (2.9%) and the manual method (2.4%). Differences in slope of the regression curves of clotting times obtained with the coagulometers over the tilt-tube method were observed with all the reagents tested (P less than 0.01). Transformation of clotting times of controls, patients with liver disease, and patients on heparin therapy to APTT ratios did not eliminate the bias resulting from the different reagents (P less than 0.001) and clot-detection methods (P less than 0.001); in controls, significant (P less than 0.001) reagent-method interaction was also observed. The in vitro heparin sensitivity differed with the APTT reagents evaluated and was influenced by the clot-detection method used. Transformation of APTT ratios of anticoagulated patients to apparent plasma heparin levels--as derived from in vitro dose-response curves--effectively eliminated the bias resulting from the different clot-detection methods but had no effect on the bias resulting from the different APTT reagents. In vitro heparin activity curves thus have little, if any, relevance for the ex vivo monitoring of heparin treatment.
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PMID:Effect of clot-detection methods and reagents on activated partial thromboplastin time (APTT). Implications in heparin monitoring by APTT. 239 4

The Ortho activated partial thromboplastin time (APTT) reagent, Thrombosil 1 (TS), was compared to the General Diagnostics automated APTT reagent (GD). TS produced more precise results over a 38-day period of testing a normal control plasma, indicating that the upper limit of the normal range could be more precisely set with TS. This normal range was better represented if the normal values with both reagents were logarithmically transformed before calculating the mean +/- 2 SD. TS was more sensitive to plasma which had been heparinized in vitro. This was also demonstrated in vivo by the testing of 100 plasmas from heparinized patients. On testing of in-vitro dilutions of normal plasma with factor-deficient plasmas, TS was more sensitive to decreasing levels of factors VIII, IX and XI but less sensitive to decreasing factor XII. This was demonstrable in vivo in 71% of cases with plasmas from factor-deficient patients. GD was more sensitive to the lupus anticoagulant in most cases.
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PMID:A comparison of two APTT reagents which use silica activators. 255 32

Two automatic coagulometers--ACL 810 (Instrumentation Laboratory), a laser-nephelometric centrifugal analyzer, and KoaguLab 40 A (Ortho Diagnostics), an optical automatic coagulometer--were compared with the manual tilt-tube method for the performance of prothrombin time (PT). Seven ISI- (International Sensitivity Index) calibrated commercial thromboplastin reagents were used for duplicate determinations in 30 normal subjects, 30 patients with liver disease, and 30 patients receiving stabilized oral anticoagulation. Clotting times were longer with the manual method than with ACL 810 and, to a lesser extent, with KoaguLab 40 A. Average imprecision of duplicate determinations (CV) was less than 1% with ACL 810; KoaguLab 40 A and the manual method had similarly higher imprecisions (2.8% and 2.7%). Differences in origin and slope of the regression curves of clotting times obtained with the coagulometers over the tilt-tube method were observed with all the reagents tested. Transformation of clotting times to PT ratios did not eliminate the bias resulting from the different clot-detection methods. A higher percentage of patients with liver disease had abnormal PT ratios when their plasma was tested with the coagulometers than with the manual method. Transformation of PT ratios to International Normalized Ratios effectively eliminated the bias resulting from the different thromboplastin reagents but had no effect on the bias resulting from the different clot-detection methods. A significant proportion of patients appeared excessively anticoagulated (INR greater than 4.5) with the coagulometers but not with the manual method. These results highlight the need for standardization of both instrumentations and reagents to improve monitoring of oral anticoagulant treatment.
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PMID:Comparison of two automated coagulometers and the manual tilt-tube method for the determination of prothrombin time. 277 51

In two open randomized studies carried out in female volunteers the effects of a new low dose oral contraceptive (O.C.) combination desogestrel + ethinylestradiol (150 micrograms/30 micrograms; Marvelon) on blood coagulation were compared with those of either the combination levonorgestrel + ethinylestradiol (150 micrograms/30 micrograms) or a triphasic preparation containing levonorgestrel + ethinylestradiol. A total of 78 women were involved in the studies which covered a period of 4 cycles; a pretreatment cycle followed by 3 treatment cycles, each consisting of 21 days of drug administration, followed by a 7-day tablet-free period. A blood sample was taken before treatment, after 2 weeks, 2 cycles and 3 cycles of treatment. The following parameters were measured: prothrombin; activated partial thromboplastin time; factors VII, VIII, X; fibrinogen; antithrombin III; euglobulin lysis time; platelet count and aggregation ratio; triglycerides and cholesterol and a glucose tolerance test was made. The effects of the different preparations on these parameters were compared statistically using either an analysis of covariance or the Wilcoxon test. No clinically significant differences were observed between the desogestrel containing preparation and the two other preparations. Any changes in treatment versus pretreatment values were slight and in agreement with the literature on other O.C.'s.
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PMID:Comparative metabolic effects of oral contraceptive preparations containing different progestagens. Effects of desogestrel + ethinylestradiol on the haemostatic balance. 315 20


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