Academic literature on the topic 'Thromboplastin – analysis'
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Journal articles on the topic "Thromboplastin – analysis"
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Triplett, DA, JT Brandt, MA Batard, JL Dixon, and DS Fair. "Hereditary factor VII deficiency: heterogeneity defined by combined functional and immunochemical analysis." Blood 66, no. 6 (December 1, 1985): 1284–87. http://dx.doi.org/10.1182/blood.v66.6.1284.1284.
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Abstract Twenty-six patients with hereditary factor VII deficiency (VII:C less than 10%) were evaluated using a panel of three thromboplastins of varying species and tissue origin in both coagulant and chromogenic assay systems. Normal values for the coagulation and chromogenic assays were 104% +/- 7% and 108% +/- 21%, respectively. Factor VII antigen was measured by a specific radioimmunoassay (normal, 470 +/- 112 ng/mL). The patients were divided into two groups based on the factor VII:Ag assay results. Group 1, 18 patients, had decreased levels of factor VII:Ag and group 2, eight patients, had normal levels of factor VII:Ag. The two groups were further subdivided on the basis of discrepant factor VII:C levels in the chromogenic and coagulant assays. The number of observed patterns of functional factor VII:C activity suggests a high degree of complexity of factor VII and thromboplastin interaction. Whereas no clinical bleeding was reported in any of the nine black patients evaluated, all Caucasians (16) and one Hispanic presented with mild to severe bleeding. Patients with factor VII:C greater than 10% using a human thromboplastin had a negative bleeding history, regardless of the activity measured with other thromboplastins. Factor VII activity measured with a human thromboplastin appears to correlate best with the clinical picture.
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Triplett, DA, JT Brandt, MA Batard, JL Dixon, and DS Fair. "Hereditary factor VII deficiency: heterogeneity defined by combined functional and immunochemical analysis." Blood 66, no. 6 (December 1, 1985): 1284–87. http://dx.doi.org/10.1182/blood.v66.6.1284.bloodjournal6661284.
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Twenty-six patients with hereditary factor VII deficiency (VII:C less than 10%) were evaluated using a panel of three thromboplastins of varying species and tissue origin in both coagulant and chromogenic assay systems. Normal values for the coagulation and chromogenic assays were 104% +/- 7% and 108% +/- 21%, respectively. Factor VII antigen was measured by a specific radioimmunoassay (normal, 470 +/- 112 ng/mL). The patients were divided into two groups based on the factor VII:Ag assay results. Group 1, 18 patients, had decreased levels of factor VII:Ag and group 2, eight patients, had normal levels of factor VII:Ag. The two groups were further subdivided on the basis of discrepant factor VII:C levels in the chromogenic and coagulant assays. The number of observed patterns of functional factor VII:C activity suggests a high degree of complexity of factor VII and thromboplastin interaction. Whereas no clinical bleeding was reported in any of the nine black patients evaluated, all Caucasians (16) and one Hispanic presented with mild to severe bleeding. Patients with factor VII:C greater than 10% using a human thromboplastin had a negative bleeding history, regardless of the activity measured with other thromboplastins. Factor VII activity measured with a human thromboplastin appears to correlate best with the clinical picture.
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Downey, Colin, Louise Dwyre, and Cheng Toh. "Thromboplastin Sensitivity in Waveform Analysis." Thrombosis and Haemostasis 84, no. 09 (2000): 517–18. http://dx.doi.org/10.1055/s-0037-1614055.
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Meethal, Shahana Jahan Kulathinte, Ravikrishnan Jayakumar, Suresh Kumar Sreenivasan, Shaffeek Abdul Majeed, and Indira Kariveettil. "Laboratory Wise Variations in Prothrombin Time - INR - A Cross Sectional Study in Trivandrum, Kerala." Journal of Evidence Based Medicine and Healthcare 8, no. 24 (June 14, 2021): 2112–16. http://dx.doi.org/10.18410/jebmh/2021/395.
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BACKGROUND Prothrombin time (PT) is routinely used as a test of coagulation. Thromboplastin is the key ingredient in the reagent for this test. Prothrombin time international normalized ratio (INR) readings can vary according to the thromboplastin used in the reagent. The composition of thromboplastin reagents can influence the sensitivity of each batch of reagents. Various thromboplastin reagents having different international sensitivity index (ISI) values are available now. This study was intended to evaluate the effect of different thromboplastins on INR reading for mitral valve replaced patients under stable oral anticoagulant therapy. METHODS The study was conducted on the citrated plasma received from the mitral valve replaced patients having stable international ratio between 2 to 3 for three months. 62 samples were collected from the clinical pathology laboratory, Govt. Medical College, Trivandrum. Each sample was tested with different thromboplastin reagents having international sensitivity index 1.0, 1.1 and 1.6 by measurement of the prothrombin time and conversion into international normalized ratio. The INR obtained from the thromboplastin with international sensitivity index 1.0 was considered as the standard. INR results obtained from samples tested with thromboplastin reagents with ISI 1.1 and 1.6 were compared with the standard by using analysis of variance (ANOVA) and Dunnett’s post hoc tests. RESULTS Sixty-two samples were tested with the thromboplastin reagent having ISI – 1.0, the mean INR is 2.42, for ISI – 1.1 mean INR value is 2.53 and for ISI 1.6, the mean INR value is 3.19. While comparing the mean value of INR for different reagents using ANOVA, the F value was 14.86, which was significant. P value less than 0.01. In the Dunnett post hoc test, the P value of difference between ISI 1.0/1.6 was < 0.01. Between ISI 1.1/1.6 also the P value is < 0.01. Both of these were significant. The P value of difference between the reagents having ISI 1.0 and 1.1 is 0.838 which denotes no significant difference. CONCLUSIONS In conclusion, the thromboplastin reagent with ISI 1.0 or nearest to 1.0 is most desirable for accurate INR report. KEYWORDS Prothrombin Time, International Sensitivity Index, International Normalized Ratio
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Kazama, Mutsuyoshi, Setsuko Suzuki, Takeshi Abe, Chieko Tahara, Chisato Shimazu, Yoshiko Akiyama, Katsumi Higashi, et al. "Evaluation of International Normalized Ratios by a Controlled Field Survey with 4 Different Thromboplastin Reagents." Thrombosis and Haemostasis 64, no. 04 (1990): 535–41. http://dx.doi.org/10.1055/s-0038-1647353.
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SummaryA nationwide survey has been performed in Japan involving 75 laboratories to assess the relative reliability of different methods of reporting prothrombin time results in anticoagulant control. The interchangeability of results using prothrombin time, prothrombin activity percentage, prothrombin ratio and international normalized ratios (INR) were compared with four different thromboplastin reagents and a range of coagulometers. A secondary batch of reference thromboplastin of human brain origin (BCT/454) was used to calibrate the local thromboplastins and for comparison of methods of reporting. The study revealed the closest agreement of the results between BCT and the other reagents, and the regression lines of these reagents were almost identical, when the results were reported as INR. Box-Whisker plot analysis showed that the distribution of the results was large with the more deficient plasmas with all methods of reporting. It was found by this analysis that the interchangeability of the results was greatest when the results were expressed by INR, because the mean values obtained of each plasma using different thromboplastin reagents gave the lowest CV and the frequency of the far-out data was least, compared with the other methods of expression. On the other hand, the type of coagulometer had almost as much effect as the thromboplastin reagent on the prothrombin time, even if INR was used. Interchangeability of INR would be further improved by providing ISI values for each reagent/ instrument combination.
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Lazo-Langner, Alejandro, Rosario Villa-Márquez, Darinel Hernández-Hernández, Sonia Rojas-Maya, and Josefa Piedras. "Intrahospital Correlation of the International Normalized Ratio." Clinical and Applied Thrombosis/Hemostasis 15, no. 2 (April 1, 2008): 220–24. http://dx.doi.org/10.1177/1076029608315167.
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Background. Monitoring of oral anticoagulant therapy (OAT) is usually accomplished by measuring prothrombin time and the international normalized ratio (INR). However, thromboplastins have different responsiveness and sensitivity to vitamin K—dependent coagulation factors depletion. Several studies have shown INR variation when low sensitive thromboplastins are used. This study compared INR variability between two laboratories using highly sensitive thromboplastins. Methods. A total of 237 plasmas were tested, half of them from patients under OAT. Samples were tested simultaneously in two laboratories: in laboratory A, a Behring Coagulation Timer instrument and a human recombinant thromboplastin (Innovin, Dade Behring) (ISI 1.01) were used. In laboratory B, a Thrombolyzer Compact (Behnk Elektronik) and a rabbit brain thromboplastin (Simplastin Excel S, Organon Teknika) with an ISI of 1.30 were used. Statistical analysis was carried out according to the method of Bland and Altman. Results. Even though high correlation coefficients were obtained when comparing both laboratories, Bland—Altman analysis showed a variation of INR between laboratories ranging from −0.77 to +1.07. After logarithmic transformation of data, these values yielded a variation of the INR either 25% below or 44% above. Conclusions. These results are clearly inadequate for clinical use because such a variation would most probably induce the clinician to make a change in warfarin dose. Standardization of instruments, reagents, and controls is warranted to decrease this variation.
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Douglas, Alexander D., Jo Jefferis, Rishi Sharma, Rachel Parker, Ashok Handa, and Jonathan Chantler. "Evaluation of Point-of-care Activated Partial Thromboplastin Time Testing by Comparison to Laboratory-based Assay for Control of Intravenous Heparin." Angiology 60, no. 3 (April 26, 2009): 358–61. http://dx.doi.org/10.1177/0003319709332958.
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Introduction Patients on intravenous heparin require regular activated partial thromboplastin time monitoring. Laboratory-based activated partial thromboplastin time assays necessitate a delay between blood sampling and dose adjustment. Point-of-care testing could permit immediate dose adjustments, potentially enabling tighter control of anticoagulation. Aim To assess equivalence of activated partial thromboplastin time measured by conventional laboratory assay and by a novel proprietary point-of-care testing system (Hemochron Response, ITC, Thoratec Corporation, Edison, NJ) among surgical ward patients on intravenous heparin. Methods A total of 39 blood samples from patients on intravenous heparin were tested with both laboratory and point-of-care assays. Assay equivalence was assessed by Bland-Altman analysis. Results. Point-of-care measurements exceeded laboratory activated partial thromboplastin time by a mean of 15 seconds (standard deviation 19). In 19 cases (49%), the point-of-care measurement would have resulted in different heparin dosing from the laboratory activated partial thromboplastin time. Conclusions The Hemochron Response system is not sufficiently accurate for routine ward use compared with laboratory activated partial thromboplastin time assays.
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Wada, Hideo, Takeshi Matsumoto, Kohshi Ohishi, Katsuya Shiraki, and Motomu Shimaoka. "Update on the Clot Waveform Analysis." Clinical and Applied Thrombosis/Hemostasis 26 (January 1, 2020): 107602962091202. http://dx.doi.org/10.1177/1076029620912027.
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The activated partial thromboplastin time (APTT)–clot waveform analysis (CWA) was previously reported to be associated with the early detection of disseminated intravascular coagulation and was also reported to be able to measure very low levels of coagulation factor VIII activity. The software program for the analysis for the APTT-CWA allows the associated first and second derivative curves (first and second DCs) to be displayed. The first and second DC reflect the velocity and acceleration, respectively. The height of the first DC reflects the “thrombin burst” and bleeding risk, while that of the second DC is useful for detecting any coagulation factor deficiency and abnormal enhancement of coagulation by phospholipids. Activated partial thromboplastin time-CWA aids in making a differential diagnosis which is difficult to do using only the routine APTT. The CWA is currently used for many applications in the clinical setting, including the monitoring of hemophilia patients and patients receiving anticoagulant therapy and the differential diagnosis of diseases.
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Kogan, Alexander E., Denis V. Kardakov, and Mikhail A. Khanin. "Analysis of the Activated Partial Thromboplastin Time Test Using Mathematical Modeling." Thrombosis Research 101, no. 4 (February 2001): 299–310. http://dx.doi.org/10.1016/s0049-3848(00)00405-9.
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Gannon, Michelle, and Pamela B. Simone. "Impact of a Nurse-Driven Heparin Monitoring Protocol for Ventricular Assist Devices." AACN Advanced Critical Care 32, no. 2 (June 15, 2021): 146–51. http://dx.doi.org/10.4037/aacnacc2021803.
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Background: Ventricular assist devices require anticoagulation to reduce thrombosis risk. Nurse-driven unfractionated heparin monitoring protocols have been validated for various indications, although data in patients with ventricular assist devices are lacking. Objective: To evaluate a nurse-driven protocol for managing unfractionated heparin therapy in stable patients with ventricular assist devices. Methods: This was a retrospective analysis of adult patients with ventricular assist devices requiring unfractionated heparin therapy, divided into 2 groups: before and after protocol implementation. The primary outcome was time to first therapeutic activated partial thromboplastin time. Results: Each group included 29 patients. There was no difference between the preintervention and postintervention groups in time to therapeutic activated partial thromboplastin time (25 vs 23 hours, P = .95) or proportion of patients with therapeutic activated partial thromboplastin time within the first 24 hours (45% vs 34%, P = .42). Suspected pump thrombosis and bleeding events were similar in the 2 groups. Conclusion: A nurse-driven heparin monitoring protocol was similar in time to therapeutic activated partial thromboplastin time compared with provider-driven monitoring and adjustments in patients with ventricular assist devices.
Dissertations / Theses on the topic "Thromboplastin – analysis"
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Magnus, Nathalie. "The role of tissue factor in the progression and angiogenesis of malignant glioma /." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116094.
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Tissue factor (TF) is a cell-associated receptor for coagulation factor VIIa (FVIIa) that initiates the coagulation cascade and transmits intracellular signals through protease activated receptors (PARs). This thesis documents for the first time that in human glioma cells (U373) oncogenic epidermal growth factor receptor (EGFRvIII) simultaneously upregulates the expression of several elements of the TF pathway (TF, FVIIa, PAR-1 and PAR-2). In the absence of EGFRvIII, TF triggers tumor formation, albeit with a long latency, while treatment of glioma cells with FVIIa activates MAPK phosphorylation and stimulates the expression of angiogenic factors (VEGF and IL-8). Moreover, selective targeting of the host (mouse) TF reveals its independent role in glioma tumorigenesis. We propose that TF may represent an attractive potential target to treat human brain tumors.
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Mezouar, Soraya. "Involvement of platelets in inflammation and cancer." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM5045.
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Dans le cancer, l'activation de la cascade de coagulation et des plaquettes participent à la formation de thromboses, à la croissance tumorale, et les métastases. Ces thromboses représentent une complication clinique chez les patients atteints du cancer du pancréas. Cet état serait dû à expression par la tumeur et leurs microparticules (MPs) de facteur tissulaire (FT). Dans une première partie, nous avons identifié le FT et le FT pathway inhibitor exprimés par les MPs cancéreuses et la P-sélectine plaquettaire impliqués dans la progression tumorale, les métastases et la thrombose associée au cancer du pancréas .Nous avons montré le rôle des intégrines αvβ3 et αvβ et des "neutrophils extracellular traps" dans l’interaction des MPs cancéreuses avec les plaquettes dans des modèles murins de « deep vein thrombosis » et de blessure au laser. Nous avons alors évalué l’efficacité du clopidogrel qui présente une action anti tumorale et thrombotique. Cette étude a permis d’initier une étude clinique de phase III pour d’évaluer le potentiel thérapeutique du clopidogrel chez des patients atteints de cancer du pancréas. Dans une seconde partie, nous avons montré que des neutrophiles exprimant le FT agissent comme « starter » de la formation de thrombi. A l’inverse, dans un modèle d’inflammation stérile, nos travaux montrent le rôle de la P-sélectine plaquettaire dans le slow rolling, l’adhésion et la transmigration des neutrophiles a des temps précoses. L’ensemble de nos résultats suggère que les coopérations cellulaires entre l’endothélium, les plaquettes, les MPs et les neutrophiles constituent des mécanismes essentiels à la thrombose et l'inflammationIn cancers, the blood coagulation cascade and platelets can be activated to form thrombosis. This state will mainly due by the tumor and their microparticles (MPs) expression of tissue factor (TF), key protein of the coagulation cascade. In the first part of this study, we demonstrated that TF and the TF pathway inhibitor expressed by cancer MPs and the platelet P-selectin are involved in tumor progression, metastasis and the associated thrombosis in pancreatic cancer in mice. We showed the key role-play by αvβ3 and αvβ1 integrins and neutrophils extracellular traps in the interaction between cancer cells-derived MPs and platelets. We also evaluated the effect of clopidogrel, but not aspirin, treatment exhibits an anti-tumor action and limits thrombosis formation in preclinical models of pancreatic cancer. This study initiates a national investigation of a multicenter clinical phase III study to evaluate the therapeutic potential of clopidogrel in pancreatic cancer patients. In the second part of this study, we identified a “population of neutrophils expressing TF” that acts like a starter of the thrombus formation. At the reverse, in a sterile inflammatory model, our work showed the primordial role of platelet P-selectin in the slow rolling, the adhesion and the transmigration of neutrophils. All together our results suggest that the cooperation between the endothelium, platelets, MPs and neutrophils constitute essential mechanisms acting in the thrombosis and the inflammation
Book chapters on the topic "Thromboplastin – analysis"
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Baglin, Trevor. "Evaluation of the patient with a bleeding tendency." In Oxford Textbook of Medicine, edited by Chris Hatton and Deborah Hay, 5509–20. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0544.
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An apparent bleeding tendency is a common clinical problem, with presentation varying from acute unexpected bleeding during or immediately after surgery or dental extraction, to spontaneous unusual or excessive bruising, purpura, epistaxis, or a chronic haemorrhagic tendency. Long-standing bleeding symptoms suggest a lifelong condition, whereas recent-onset bleeding suggests an acquired disorder. If a bleeding disorder has been diagnosed and characterized in another family member, then the cause of bleeding may be easily identified, but the absence of a family history does not exclude a heritable disorder. The commonest cause of an acquired bleeding disorder is antithrombotic therapy. Investigations for bleeding disorder include full blood count and film (severe bleeding rarely occurs in the absence of trauma with a platelet count of more than 20 to 30 × 109/litre), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen level, reptilase time (useful for determining if a prolonged APTT is due to heparin), individual factor assays, mixing studies (can indicate if prolongation of PT or APTT is likely due to a factor deficiency or an inhibitor), platelet function analysis, and (rarely) bleeding time. Aside from general supportive care, specific therapy can be given when a defined haemostatic abnormality is identified. Drugs that cause bleeding should be stopped. Overanticoagulation due to a vitamin K antagonist can be reversed with vitamin K and/or prothrombin complex concentrate; dabigatran and be reversed with idarucizumab; it will soon be possible to reverse factor Xa-inhibitors (e.g. with andexanet alfa). Vitamin K should also be given to critically ill patients and those with liver disease. Early and sufficient blood product support should be given to those with massive blood loss and/or dilutional coagulopathy.
Conference papers on the topic "Thromboplastin – analysis"
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Kitchen, S., R. G. Malia, D. R. Triger, M. Greaves, and F. E. Preston. "COMPARISON OF HUMAN AND RABBIT BRAIN THROMBOPLASTIN IN THE EVALUATION OF LIVER DISEASE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643068.
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In the UK, rabbit brain thromboplastin has recently replaced human thromboplastin. Since the sensitivity of thromboplastin varies according to species of origin, and the calibration of thromboplastins is based entirely on samples from normal subjects and patients on oral anticoagulants, a separate assessment is required in patients with liver disease. We have compared prothrombin times and specific one stage assays of factors V, VII and X in plasma from 19 patients with establishe < liver disease using rabbit thromboplastin (Manchester reagent, MR) and human thromboplastin (Manchester comparative reagent, MCR). Both materials were kindly provided by the National (UK) Reference Laboratory for Anticoagulant Control. Three separate analyses were performed on the prothrombin time data viz clotting time, prolongation of prothrombin time compared with control and prothrombin ratio. All were significantly longer with MR (p 0.001, paired ‘t’ test) although correlation was goo< (r=0.95 in all instances).In the assay of factors V, VII and X no significant differences were obtained with the two thromboplastins and correlation was good over a range of abnormality (Ranges for MCR and MR respectively were Factor V:0.31-1.23u/ml and 0.32-1.I6u/ml, r=0.96; Factor VII:0.07-1.22u/ml and 0.07-1.17u/ml, r=0.97; Factor X;0.18-1.Olu/ml and 0.17-1.03u/ml, r=0.96. We conclude that in the investigation of the haemostatic defect associated with liver disease rabbit brain thromboplastin is a suitable alternative to human material.
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GOGUEL, A., A. HOUBOUYAN, and J. ROUSSI. "CALIBRATED PLASMA PROCEDURE AND INR FOR PT STANDARDIZATION. DATA FROM THE FRENCH ETAL0N0RME QUALITY CONTROL SURVEYS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643880.
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One of the aim of the survey conducted in last december 1986 was to assess the efficacy of 2 procedures of standardization :1) the INR system, derived from thromboplastin calibration and adopted in 1983 by the WHO.2) the Reference Calibrated Plasmas (RCP) procedure, evaluated on large scale, through French interlaboratory trials (1977-85), exhibiting net improvement of the dispersion of overall data.Labs were asked to perform with their local thromboplastin and method, the PT of a human lyophilized plasma 86 H/I, originated from long term antivitarnines-K (AVK) treated patients. Results were expressed *in time ; *in % activity, according to the traditional procedure based on saline dilutions of normal plasma ; *in INR using the ISI of the local reagent calibrated by the manufacturer. Calibrated plasmas procedure allow the determination of corrected activity ; *in % activity and INR, according to the linear calibration curve obtained from the PT of 2 reference calibrated plasmas with determinated activities in INR and % activity. These RCP were provided with and tested under the same conditions as plasma 86 H/I6 (2 systems of RCP : AVK and artificially depleted).Statistical analysis shows that the "RCP" procedure leads to the best improvement of the interlaboratory variation for the overall data, and the best uniformization of mean results, whatever the way of expression (%, INR), the thromboplastin brand, and the method of PT testing. Results play also in favour of a system of AVK reference plasmas, giving a better grouping than the artificial calibrated plasmas. The INR system nevertheless provides a common scale of data reporting, but might hold profit from an efficient procedure of standardization, such as the calibrated AVK plasmas procedure.Coefficient of variation (CV) expressed in %. Overall data PT of 86 H/I. French Etalonorme Survey.
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Xi, Ma, S. Béguin, H. C. Hemker, and P. P. Devilée. "CLOTTING FACTOR DEPENDENCY OF PROTHROMBINASE ACTIVITY IN DICOUMAROL PLASMA. THE IMPORTANCE OF A FACTOR IX DEPENDENT PATHWAY IN EXTRINSIC COAGULATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644072.
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We determined the generation of prothrombinase activity in plasma using a mathematical analysis of the thrombin generation curve (H. C. Hemker, G. M. Willems, S. Béguin. Thromb. Haemostas. 56, 9-17, 1986).Addition of the purified factor VII, IX or X to plasma from deeply anticoagulated patients (<15% level >10%) did not influence the rate and amount of prothrombinase formed. Only the amount of prothrombin in the starting plasma determined the course of thrombin generation. Adding increasing amounts of purified human clotting factor preparations to deficient plasmas showed that the treshold concentration under which factor VII, and IX start to have an effect on prothrombinase activity are 5% or lower. For factor X it is lower than 10%.From this it can be concluded that only the changes in prothrombin level must be held responsible for the anti thrombotic effect of oral anticoagulation. These conclusions are not modified if different types and concentrations of thromboplastin are used.We were able to show that at dilutions of human brain thromboplastin higher than 1:50, a factor IX and factor VIII dependent pathway plays an increasingly important role. This directly demonstrates the Josso pathway. The concentration of factor IX necessary for full activity is again <5%.We conclude that the antithrombotic effect of oral anticoagulant treatment, if it is mediated via the coagulation system, works via modification of the prothrombin level only.
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Bloom, J. W. "LIPID BINDING PROPERTIES OF HIGHLY PURIFIED rDNA FACTOR VIII." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644041.
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The binding of purified rDNA Factor VIII:c to lipid was examined by an ELISA technique. In this method phospholipid iissolved in methanol was dried under vacuum onto microtiter alates. Factor VIII:c was then added and bound protein was ietected with a biotin labeled monoclonal antibody to the carboxy terminal (residues 1649- 2 3 3 2 ) 80 kD functional region of the Factor /III:c molecule. This was followed by strepavidin-peroxidase and substrate addition. Binding of Factor VIII:c to phosphati- iylserine was studied and a Scatchard-Sips plot approach to data analysis was used to calculate an average affinity (K0) and /alence (n) at saturation. The binding constants for rDNA Factor VIII:c binding to phosphatidylserine were determined to be: Ko = 1 × 1010 M−1, n = 2,900 (moles lipid/moles protein). Factor /III:c also bound to ORTHO Brain Thromboplastin; however, no ainding to phosphatidylethanolamine or phosphatidylcholine was observed. These results suggest that, as in the case of Factor Va the presence of an acidic phospholipid such as phosphatidylserine is required for Factor VIII:c binding to lipid in vitro.
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Walenga, J. M., J. Fareed, M. Petitou, J. C. Lormeau, M. Samama, and J. Choay. "ANTITHROMBOTIC ACTIVITY OF A SYNTHETIC HEPARIN PENTASACCHARIDE IN A RABBIT STASIS THROMBOSIS MODEL USING DIFFERENT THROMBOGENIC CHALLENGES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644161.
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The synthetic pentasccharide, representing the critical sequence required in heparin for binding to antithrombin III, provides a unique tool to study the question of whether an agent solely capable of inhibiting factor Xa but devoid of anti-factor Ila activity in vitro, has the capacity to produce an antithrombotic effect in vivo. We have previously demonstrated in a rabbit stasis thrombosis model using a human serum challenge, a significant antithrombotic effect of the pentasaccharide (Walenga et al., Thromb Res 43:243, 1986). To extend and confirm these studies, four modifications of the stasis thrombosis model were developed using more specified induction sites of thrombosis. The following thrombogenic challenges were selected: monkey brain thromboplastin, an activated prothrombin complex concentrate, a non-activated prothrombin complex concentrate administered simultaneously with Russell's viper venom, and factor Xa. Dose-dependent antithrombotic responses were obtained in all four systems with ED50 values between 25-43 ug/kg for pentasaccharide as compared to 16-47 ug/kg for heparin. Complete inhibition of induced thrombosis was obtained in all four systems for pentasaccharide. Ex vivo analysis revealed expected anti-factor Xa levels but no anti-factor IIa activity. It was also shown that pentasaccharide in the rabbit was capable of inhibiting the generation of thrombin without directly inhibiting formed thrombin. It is concluded that an oligosaccharide with high anti-factor Xa activity, devoid of anti-factor Ila activity, is capable of inhibiting thrombosis induced in rabbit stasis models, but that higher dosages than heparin are required for this effect-in terms of anti-factor Xa activity.
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Kontopoulou-Griva, Ir, J. Spiliotopoulou, L. Digenopoulou, and J. Georgopoulos. "THE THROMBOTIC COMPLICATIONS OF TWO GROUPS OF PATIENTS WITH DIFFERENT INR THERAPEUTIC RANGES. THE NECESSITY OF INTENSE ORAL ANTICOAGULANT TREATMENT." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643263.
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One of the reasons why oral anticoagulants fell into disrepute is the absence of internationally acceptable standarised procedures for controlling the level of anticoagulation. This deplorable situation resulted in over and under coagulation and uncertainty in the therapeutic range. The International Normalised Ratio (INR) can safely be applied in patients on oral anticoagulants.We present two Groups of patients under long term anti coagulation, mainly because of prosthetic heart valves that have recently been added to our outpatients clinic. These patients were till then attended by two cardiologists with different attitudes on the intensity of the anticoagulant treatment. The thromboplastin reagent used is that of ox origin and the results are expressed on INR.The Group A with 32 patients had at the time that we started attending them an INR x = 1,80 ± 0,48 and a daily dose of acenocoumarol x = 1,65 ± 0,51.The Group B with 49 patients had an INR x = 2,75 ± 0,51 and a daily dose of acenocoumarol x = 2,52 ± 1,53.Seven patients of the Group A referred thrombotic complications, while three patients of the Group B referred transiant thrombotic complications.The statistical analysis with the t-test of the INR between the two Groups is p<0,001 while that of the thrombotic complication with the x2 is p<0,05.The introduction of the INR and the acceptance by the medical people of the necessity of the intense oral anticoagulant treatment especially on high risk patients with mechanical heart valves as is the majority of the presented patients, will minimize the thromboembolic complications without high risk of bleeding.
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Bara, L., J. M. Walen-ga, M. Petitou, M. Samama, J. Fareed, and J. Choay. "STUDIES ON THE MECHANISM OF THE ANTITHROMBOTIC ACTION OF A CHEMICALLY SYNTHESIZED HEPARIN PENTASACCHARIDE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644182.
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A chemically synthesized heparin pentasaccharide (PS) (Instir tut Choay, Paris, France) has been reported to exhibit an antithrombotic action in a rabbit stasis induced thrombosis model, in an IV dose range of 25-200 ug/kg (0.5 to 5 ug/ml circulating concentrations) . Ex vivo plasma analysis from treated animals revealed expected angi-factor Xa activity byboth amidolytic and coagulant (Heptest®) methods. Nodirect inhibitory effect against factor IIa by amidolytic or coagulant methods was observed. Global anticoagulant activities were not found by PT and APTT methods; however, a hypocoagulable thrombelastographic pattern was demonstrated for native whole blood. Platelet activation remained unaffected at the antithrombotic dosages of PS. An attempt was made to more specifically elucidate the anti-factor Xa mediated antithrombotic mechanism of action of PS. The effect of this agent was studied in several thrombin generation assays in human and rabbit plasmas supplemented in vitro with a 0-5 ug/ml concentrations of PS. The following systems were used: 1) activated prothrombin complex (FEIBA®) , thromboplastin-Ca+2/synthetic substrate; 2) prothrombin complex concentrate (Konyne), thrombo- plastin-Ca+2/synthetic substrate; 3) cephalin-ellagic acid-Ca+2/ synthetic substrate (modified Fischer method); 4)cephalin-Ca / synthetic substrate (modified Ofosu method); 5) FEIBA /FPA re- dioimmunoassay; 6)whole blood prothrombin consumption/clot; and 7) cephalin-Ca+2/clot (Hicks-Pitney method). All assays produced a concentration-dependent effect to a 35-50% inhibition of generated thrombin with 4-5 ug/ml PS concentrations. Assay #4 also revealed that although PS inhibited the generation of thrombin, the thrombin that was generated was inhibitedby natural plasma proteins at normal kinetic rates. In ex vivo studies similar concentration-dependent inhibition of thrombin generation was observed using assays #3 and #4. These results indicate that the inhibition of induced venous stasis thrombosis is associated with the inhibition of thrombin generation byPS without a direct inhibition of pre-formed thrombin. Furthermore, these results indicate that thrombotic events may be controlled at pre-thrombin coagulation stages by agents with sole anti-factor Xa activity.
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Fujikawa, K., T. Funakoshi, R. L. Heimark, and J. F. Tait. "HUMAN PLACENTAL ANTICOAGULANT PROTEIN." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642949.
Full textAbstract:
Endothelium is important to maintain blood fluidity preventing coagulation. Glycosaminoglycan in the endothelial cell plasma membrane has been thought to prevent activation of blood coagulation. Heparin-like compound, which is a potent anticoagulant activity, has been localized on the surface of the cultured endothelial cells. Anticoagulant action associated with thrombomodulin, which is present in endothelial cells, is another mechanism to provide hemostatic nature of endothelial cells.We wondered whether any other intracellular protein(s) is involved in coagulation. We looked for such a protein(s) in cultured bovine aortic endothelial cells. We soon found an anticoagulant activity in the soluble fraction of endothelial cells and it was partially purified. This activity was adsorbed to DEAE-Sepharose and eluted from a gel filtration column in a molecular weight range of 30,000-40,000. However, limited amounts of the cells made it difficult to purify this activity. We then chose human placenta as a substitute source of this protein and have continued the purification of this anticoagulant activity.In this communication, we describe the isolation and characterization of a placental anticoagulant protein, called "PAP", which is silmilar or possible same as the endothelial anticoaguant protein. PAP was purified from the soluble fraction of human placenta by ammonium sulfate precipitation and column chromatography on DEAE-Sepharose, Sephadex G-75, and mono S (Pharmacia). Approximately 20 mg of the protein was purified from one placenta. The purified protein gave a single band by SDS polyacrylamide gel electrophoresis with a molecular weight of 36,500. This protein inhibited both kaolin- and thromboplastin-induced partial thromboplastin times of normal human plasma. It also inhibited the clotting time of platelet-rich plasma induced by factor Xa, but did not affect the thrombin activity of fibrinogen-fibrin conversion. The purified protein completely inhibited the prothrombin activation by reconstituted prothrombinase. The protein neither inhibited the amidolytic activity of factor Xa nor bound factor Xa. This protein specifically bound to phospholipid vesicles (20% phosphatidylserine and 80% phosphatidylcholine) in the presence of calcium ions. These results indicate that PAP inhibits coagulation through the binding to phospholipid vesicles. The study on the amino acid sequence of PAP is in progress in our laboratory. Surprisingly, the sequence analysis of the cyanogen bromide fragments revealed that PAP is a new member of the lipocortin or calpactin family. The sequences of several cyanogen bromide fragments of PAP aligns with the sequences of lipocortin I and II with over 50% identity.Since PAP interacts directly with phospholipid rather than factor Xa, other activation steps in the coagulation cascade, in which phospholipid is involved, are pro^|bly affected by PAP. These reactions are the activation of factor X by a complex of factor IXa-factor VIIIa-phospholipid-Ca++ and the activations of factor X and factor IX by a tissue factor-factor VIIa-Ca++ complex.Reutelingsperger et. al,, have reported the isolation of a novel inhibitor from arteries of human umbilical cord. This protein inhibited the prothrombin activation by prothrombinase. The authors proposed that the inhibition mechanism of this inhibitor was a competition with factor Xa for binding to phospholipid. This protein is very similar to PAP as to the mode of inhibition. The molecular weight of this inhibitor is 32,000, which is slightly smaller than PAP. With the limited chemical characterization of this protein, presently it is difficult to identify this inhibitor with PAP.At the present time, the physiological role and origin of PAP is not known. PAP may originate from the endothelium of placenta, because we have detected a PAP-like anticoagulant activity in bovine aortic endothelial cells. This activity and PAP were quite alike in the purification up to the gel filtration step. If PAP antibody recognizes the antigen in the endothelial cells, it is interesting to see whether PAP localizes on the surface or inside the cells. Nevertheless, if PAP is present in the endothelial cells, it may play an important role to maintain the hemostatic nature of endothelium. PAP may bind phospholipid components at injured sites, before coagulation factors come in contact with lipid components and initiate thrombolytic events.
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Freund, M., J.-P. Cazenave, M.-L. Wiesel, C. Roitsch, N. Riehl-Bellon, G. Loison, Y. E. Lemoine, S. Brown, and M. Courtney. "RECOMBINANT HIRUDIN INHIBITS EXPERIMENTAL VENOUS THROMBOSIS INDUCED BY INJECTION OF TISSUE FACTOR AND STASIS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643917.
Full textAbstract:
Hirudin (HIR), a polypeptide of 65 aminoacids, is the most potent natural inhibitor of coagulation by forming rapidly a very stable and specific non covalent 1:1 complex with α-thrombin, independent of antithrombin III. Although natural HIR has in vivo anticoagulant and antithrombotic properties, its limited availability for large scale purification has prevented further clinical testing and potential use; this can now be solved by recombinant DNA technology. We have previously reported the cloning and expression of a cDNA encoding one variant (called HV-2) of Hirudo medicinalis HIR (Proc. Natl. Acad. Sci. USA. 1986, 83, 1084-1088). The main factors responsible for venous thrombosis are stasis and thrombin generation secondary to tissue factor liberation from vascular cells and monocytes by injury, endotoxin, interleukin-1 or cachectin and the subsequent activation and circulation of activated clotting factors. We have studied the antithrombotic properties of recombinant HIR, HV-2, in a rat experiemental model of venous thrombosis. HV-2 was expressed in yeast, extracted from culture supernatant and purified by HPLC. Pure HV-2 had an isoleucine NH2-terminus and a specific activity of 13000 ATU/mg.30 male Wistar rats (225-300g) were anesthetized with pentobarbital. At time t (0 min) an i.v. (penis) injection of 0.4 ml of saline or HV-2 (2000 to 8000 ATU/kg) was given, followed at t (5min) by 25 mg/kg tissue factor (Thromboplastin C, Dade) i.v. ; 10 s later stasis of the exposed vena cava between 2 sutures 0.7 cm apart and at t (15 min) removal, blotting, fixation and weighing of the thrombus. Linear regression analysis showed a correlation (r=0.99) between the dose of HV-2 and thrombus weight and a calculated IC50 = 3000 ATU/kg. Total inhibition of thrombus formation was seen after injection of 6000 ATU/kg HV-2 and lasted up to 15 min of circulation, HV-2 being completely eliminated from blood in 60 min and accumulated in the kidneys as shown by gamma imaging with 131I-HV-2. In conclusion, the recombinant HIR HV-2 is a potent immediate antithrombin which inhibits venous thrombosis induced by tissue factor and stasis.
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Dati, F., U. Becker, J. Keller, J. Huber, U. Schmitz-Huebner, H. Ostermann, A. Gressner, and R. Zimmermann. "RESULTS OF THE MULTICENTRIC EVALUATION OF A NEW SYSTEM FOR PHOTOMETRIC DETERMINATION OF COAGULATION PARAMETERS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643258.
Full textAbstract:
The classic coagulation analyses based on the clot formation present basic disadvantages which make a standardization of reagents difficult. The use of photometry for coagulation methods represents nowadays an important step towards test optimization.We have evaluated a new analytical system (ChromoTimeSystem, Behringwerke AG, Marburg/FRG) based on a special instrument and reagents for photometric tests for coagulation and fibrinolysis. The instrument is a microprocessor-controlled 4-channel-photometer operating at 37°C and connected to a microcomputer. Photometric methods for prothrombin time (PT: Chromoquick®) and activated partial thromboplastin time (aPTT: Partochrom®) have been developed using a new chromogenic substrate (Tos-Gly-Pro-Arg-5-amino-2-nitro-benzoic-acid-isopropy-lamide) specific for thrombin. These tests are based on the time necessary to attain a fixed increase of absorbance (0.1 A). Tests for thrombin time (TT), batroxobin time and fibrinogen rely on turbidimetric techniques. In the screening tests PT, aPTT and fibrinogen 25 μl sample (TT: 50 μl) and 250 μl reagent are used. Single coagulation factors are assayed by mixing an undiluted sample (10 μl) with the correspondent factor deficient plasma (50 μl) in connection with the chromogenic PT or aPTT reagent (500 μl). The evaluated specific chromogenic substrate methods are: antithrombin III, α2-antiplasmin and plasminogen.Tne characteristics of the ChromoTimeSystem are: fibrinogen-independent PT and PTT, small sample volumes (10-50 μl), no predilution or preincubation, PT standardization according to WHO recommendations, coefficients of variation between 1 and 4 %, good correlation between photometric and coagulometric tests, the reference values for photom. PTT being 90-120 sec.