scholarly journals Thrombin Inhibition by Argatroban: Potential Therapeutic Benefits in COVID-19

Author(s):  
Kholoud F. Aliter ◽  
Rami A. Al-Horani
2013 ◽  
Author(s):  
J. Bobrow ◽  
E. Cook ◽  
C. Knowles ◽  
C. Vieten

1988 ◽  
Vol 60 (02) ◽  
pp. 188-192 ◽  
Author(s):  
F A Ofosu ◽  
F Fernandez ◽  
N Anvari ◽  
C Caranobe ◽  
F Dol ◽  
...  

SummaryA recent study (Fernandez et al., Thromb. Haemostas. 1987; 57: 286-93) demonstrated that when rabbits were injected with the minimum weight of a variety of glycosaminoglycans required to inhibit tissue factor-induced thrombus formation by —80%, exogenous thrombin was inactivated —twice as fast in the post-treatment plasmas as the pre-treatment plasmas. In this study, we investigated the relationship between inhibition of thrombus formation and the extent of thrombin inhibition ex vivo. We also investigated the relationship between inhibition of thrombus formation and inhibition of prothrombin activation ex vivo. Four sulfated polysaccharides (SPS) which influence coagulation in a variety of ways were used in this study. Unfractionated heparin and the fraction of heparin with high affinity to antithrombin III potentiate the antiproteinase activity of antithrombin III. Pentosan polysulfate potentiates the activity of heparin cofactor II. At less than 10 pg/ml of plasma, all three SPS also inhibit intrinsic prothrombin activation. The fourth agent, dermatan sulfate, potentiates the activity of heparin cofactor II but fails to inhibit intrinsic prothrombin activation even at concentrations which exceed 60 pg/ml of plasma. Inhibition of thrombus formation by each sulfated polysaccharides was linearly related to the extent of thrombin inhibition achieved ex vivo. These observations confirm the utility of catalysis of thrombin inhibition as an index for assessing antithrombotic potential of glycosaminoglycans and other sulfated polysaccharides in rabbits. With the exception of pentosan polysulfate, there was no clear relationship between inhibition of thrombus formation and inhibition of prothrombin activation ex vivo.


1994 ◽  
Vol 72 (06) ◽  
pp. 874-879 ◽  
Author(s):  
Jean Millet ◽  
Jocelyne Theveniaux ◽  
Neil L Brown

SummaryThe venous antithrombotic profile of naroparcil or (4-[4-cyanoben-zoyl]-phenyl)-1.5-dithio-β-D-xylopyranoside was investigated in the rabbit following single i. v. and oral administration. Naroparcil attenuated thrombus development in a Wessler stasis model of venous thrombosis (jugular vein) employing bovine factor Xa as a thrombogenic stimulus giving ED50 values of 21.9 mg/kg and 36.0 mg/kg after respectively i. v. and oral administration. Venous antithrombotic activity was maximal 2-3 h after i. v. administration and 4-8 h after oral administration. Four hours after the oral administration of maximal antithrombotic (Wessler model, factor Xa) doses (100 and 400 mg/kg), naroparcil had no significant effect on bleeding time. In platelet poor plasma obtained from animals treated 4 h previously with various doses (25 to 400 mg/kg) of naroparcil, there was no detectable anti-factor Xa nor antithrombin activity. Similarly, naroparcil had no effect on APTT nor on thrombin time. A sensitized thrombin time (to about 35 s) was modestly but significantly increased following oral administration of the compound at 400 mg/kg. However, thrombin generation by the intrinsic pathway was reduced in a dose-related manner, maximal reduction being 65% at 400 mg/kg. The same doses of naroparcil enhanced the formation of thrombin/heparin cofactor II complexes at the expense of thrombin/antithrombin III complexes in plasma incubated with (125I)-human a-thrombin and induced the appearance of dermatan sulfate-like material in the plasma of treated rabbits, as measured by a heparin cofactor II-mediated thrombin inhibition assay. The results suggest that naroparcil could have a safe venous antithrombotic profile following oral administration (antithrombotic effect compared to bleeding risk). It is probable that part of the mechanism of action of the β-D-xyloside, naroparcil, is due to the induction of chondroitin sulfate-like glycosaminoglycan biosynthesis, this material being detectable in the plasma.


1980 ◽  
Vol 44 (02) ◽  
pp. 092-095 ◽  
Author(s):  
T H Tran ◽  
C Bondeli ◽  
G A Marbet ◽  
F Duckert

SummaryTwo different AT-III fractions were purified from the plasma of a patient with recurrent superficial thrombophlebitis. The abnormal AT-III fraction (A-AT) was compared to the normal AT-III fraction (N-AT) in the inhibition of thrombin and factor Xa. Without heparin, both inactivate proteases in a similar manner and at the same rate. However, at low heparin concentration the thrombin inhibition proceeds more slowly with A-AT than with N-AT. At high heparin concentration the difference between A-AT and N-AT becomes very small. The inhibition of factor Xa follows a similar pattern. It is suggested that the heparin binding site of A-AT differs from that of N-AT resulting in a decreased heparin cofactor activity.


1982 ◽  
Vol 48 (01) ◽  
pp. 101-103 ◽  
Author(s):  
B Kirchhof ◽  
J Grünwald

SummaryEndothelial and smooth muscle cells cultured from minipig aorta were examined for their inhibitory activity on thrombin and for their thrombin generating capacity.Endothelial cells showed both a thrombin inhibition and an activation of prothrombin in the presence of Ca++, which was enhanced in the presence of phospholipids. Smooth muscle cells showed an activation of prothrombin but at a lower rate. Both coagulation and amidolytic micro-assays were suitable for studying the thrombin-vessel wall interaction.


1982 ◽  
Vol 48 (01) ◽  
pp. 084-086
Author(s):  
Wayne W Fish ◽  
Ingemar Björk

SummaryThe extent of inhibition of thrombin was re-examined as a consequence of the sequence of addition of thrombin and antithrombin III to a column of heparin immobilized on agarose. With the use of pure enzyme, pure inhibitor, and a highly sensitive chromogenic substrate, no appreciable difference in the extent of thrombin inhibition was observed between the two sequences of addition. These observations, together with a demonstrated sensitivity of the method to variations in experimental protocol, challenge the conclusions reached in an earlier work (Hatton and Regoeczi, Thromb. Res. 1977; 10:645) which utilized this experimental approach but which employed larger quantities of reactants and a less sensitive substrate.


1984 ◽  
Vol 52 (02) ◽  
pp. 148-153 ◽  
Author(s):  
D P Thomas ◽  
A D Curtis ◽  
T W Barrowcliffe

SummaryAn international collaborative study, in which 22 laboratories participated, was carried out to establish a replacement for the International Standard for Heparin. A total of 248 assays were analyzed, including APTT, thrombin inhibition and anti-Xa assays, as well as pharmacopoeial assays. Overall, there was less than 5% difference in the mean potency estimates of the candidate preparations, by all assay methods. The freeze-dried preparation 82/502 demonstrated the closest parallelism by bioassay to the existing standard and was established by WHO as the 4th International Standard for Heparin, with an assigned unitage of 1780 i.u. per ampoule.


2019 ◽  
Vol 15 (1) ◽  
pp. 40-52
Author(s):  
Nana Aba Appiah Amfo ◽  
Ekua Essumanma Houphouet ◽  
Eugene K. Dordoye ◽  
Rachel Thompson

The present paper examines interactions in psychiatric care consultation in selected hospital settings in three Akan-speaking communities in Ghana, based on 45 audio-recorded doctor/nurse-patient interactions. Using a discourse pragmatics approach, we note how language is used in the management of communication in psychiatric consultations, and how the dominance of healthcare practitioners is enacted. Specifically, we focus on some of the strategies used by the participants to manage the multilingual communicative settings, such as code-mixing. Our findings also suggest that the use of proverbs as a diagnostic tool in psychiatric consultations in Ghana needs to be reviewed. We propose that in order for patients to experience consultation sessions that are more interactive, with possible therapeutic benefits, health practitioners need to make considerable efforts to involve the patients in decisions regarding their health.


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