Effect of dalteparin administration on thrombin generation kinetics in healthy dogs

2017 ◽  
Vol 46 (2) ◽  
pp. 269-277 ◽  
Author(s):  
Carolyn Gara-Boivin ◽  
Jérôme R.E. de Castillo ◽  
Marilyn E. Dunn ◽  
Christian Bédard
Keyword(s):  
Thrombin Generation ◽  
Healthy Dogs

Reproducibility, stability, and biological variability of thrombin generation using calibrated automated thrombography in healthy dogs

2018 ◽  
Vol 47 (2) ◽  
pp. 218-226 ◽  
Author(s):  
Benoît Cuq ◽  
Shauna L. Blois ◽  
R. Darren Wood ◽  
Gabrielle Monteith ◽  
Anthony C. Abrams-Ogg ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Biological Variability ◽  
Healthy Dogs

scholarly journals Thrombin generation and thromboelastometry tests in dogs with chronic kidney disease

2020 ◽  
Vol 40 (2) ◽  
pp. 113-120
Author(s):  
Daniele S. Gonçalves ◽  
Silvano S. Geraldes ◽  
Rita Carolina F. Duarte ◽  
Maria das Graças Carvalho ◽  
Priscylla Tatiana C. Guimarães-Okamoto ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Viscoelastic Properties ◽  
Thrombin Generation ◽  
Control Group ◽  
Fibrinogen Concentration ◽  
Discrete State ◽  
Significance Level ◽  
Bleeding Episodes ◽  
Healthy Dogs

ABSTRACT: Patients with chronic kidney disease (CKD) have paradoxical hemostatic potential because they have bleeding episodes but are also prone to thrombosis. Few studies have evaluated blood viscoelastic properties in dogs with kidney disease; on the other hand, hypercoagulability has been observed in these patients. It is also emphasized that the platelet function and its participation in this process have not yet been fully understood. The objective of this study was to evaluate and compare the Thrombin Generation Test (TGT) and also viscoelastic properties of the blood measured by thromboelastometry (TEM) in dogs with proteinuria in CKD. Twenty healthy dogs (Control Group) and 19 dogs with CKD in stage III or IV, classified according to International Renal Interest Society - IRIS, were selected, and the reference test of urine protein:creatinine ratio (UPCR) should be greater than one (CKD group). Blood samples for TEM, thrombin generation, Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), and fibrinogen concentration was collected at a single time for both groups after inclusion criteria being confirmed. Statistical analysis was performed according to the distribution of variables at 5% significance level. Differences were observed between healthy dogs and those with proteinuria in CKD noted in TEM. The TGT was unable to differentiate between sick and healthy groups. However, when the nephropathy was stratified, increases in TTP and peak thrombin concentration by TGT were observed in females and dogs over 30 days of diagnosis of CKD. Both tests signaled a discrete state of hypercoagulability. In fact, TEM is more sensitive to detect hypercoagulability in dogs with CKD. However, the TGT has potential clinical application by allowing long-term sample storage.

Thrombin generation and inhibition in the mediation of ischemic neuronal death

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S19-S19
Author(s):  
Marlise de Castro Ribeiro ◽  
Jerome Badaut ◽  
Melanie Price ◽  
Marita Meins ◽  
Julien Bogousslavsky ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Thrombin Generation

Thrombin generation in paediatric patients with congenital heart disease

2008 ◽  
Vol 28 (S 01) ◽  
pp. S61-S66 ◽  
Author(s):  
G. Cvirn ◽  
A. Rosenkranz ◽  
B. Leschnik ◽  
W. Raith ◽  
W. Muntean ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Negative Correlation ◽  
Congenital Heart ◽  
Thrombin Generation ◽  
Significant Negative Correlation ◽  
Peak Height ◽  
Global Test ◽  
Paediatric Patients ◽  
Age Range

SummaryThrombin generation was studied in paediatric patients with congenital heart disease (CHD) undergoing cardiac surgery using the calibrated automated thrombography (CAT) in terms of the lag time until the onset of thrombin formation, time to thrombin peak maximum (TTP), endogenous thrombin potential (ETP), and thrombin peak height. The suitability to determine the coagulation status of these patients was investigated. Patients, material, methods: CAT data of 40 patients with CHD (age range from newborn to 18 years) were compared to data using standard coagulation parameters such as prothrombin (FII), antithrombin (AT), tissue factor pathway inhibitor (TFPI), prothrombin fragment 1.2 (F 1.2), thrombin-antithrombin (TAT), activated partial thromboplastin time (aPTT), and prothrombin time (PT). Results: A significant positive correlation was seen between ETP and FII (p < 0.01; r = 0.369), as well as between peak height and F II (p < 0.01; r = 0.483). A significant negative correlation was seen between ETP and TFPI values (p < 0.05; r = –0.225) while no significant correlation was seen between peak height and TFPI. A significant negative correlation was seen between F 1.2 generation and ETP (p < 0.05; r = –0.254) and between F 1.2 generation and peak height (p < 0.05; r = –0.236). No correlation was seen between AT and ETP or peak. Conclusions: CAT is a good global test reflecting procoagulatory and inhibitory factors of the haemostatic system in paediatric patients with CHD.

Ancylostoma caninum Anticoagulant Peptide Blocks Metastasis In Vivo and Inhibits Factor Xa Binding to Melanoma Cells In Vitro

1998 ◽  
Vol 79 (05) ◽  
pp. 1041-1047 ◽  
Author(s):  
Kathleen M. Donnelly ◽  
Michael E. Bromberg ◽  
Aaron Milstone ◽  
Jennifer Madison McNiff ◽  
Gordon Terwilliger ◽  
...  
Keyword(s):  
Active Site ◽  
Thrombin Generation ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Melanoma Cells ◽  
Factor V ◽  
Ancylostoma Caninum ◽  
Metastatic Activity

SummaryWe evaluated the in vivo anti-metastatic activity of recombinant Ancylostoma caninum Anticoagulant Peptide (rAcAP), a potent (Ki = 265 pM) and specific active site inhibitor of human coagulation factor Xa originally isolated from bloodfeeding hookworms. Subcutaneous injection of SCID mice with rAcAP (0.01-0.2 mg/mouse) prior to tail vein injection of LOX human melanoma cells resulted in a dose dependent reduction in pulmonary metastases. In order to elucidate potential mechanisms of rAcAP’s anti-metastatic activity, experiments were carried out to identify specific interactions between factor Xa and LOX. Binding of biotinylated factor Xa to LOX monolayers was both specific and saturable (Kd = 15 nM). Competition experiments using antibodies to previously identified factor Xa binding proteins, including factor V/Va, effector cell protease receptor-1, and tissue factor pathway inhibitor failed to implicate any of these molecules as significant binding sites for Factor Xa. Functional prothrombinase activity was also supported by LOX, with a half maximal rate of thrombin generation detected at a factor Xa concentration of 2.4 nM. Additional competition experiments using an excess of either rAcAP or active site blocked factor Xa (EGR-Xa) revealed that most of the total factor Xa binding to LOX is mediated via interaction with the enzyme’s active site, predicting that the vast majority of cell-associated factor Xa does not participate directly in thrombin generation. In addition to establishing two distinct mechanisms of factor Xa binding to melanoma, these data raise the possibility that rAcAP’s antimetastatic effect in vivo might involve novel non-coagulant pathways, perhaps via inhibition of active-site mediated interactions between factor Xa and tumor cells.

Fibrinogen and its Derivatives: Cofactors in the Intrinsic Generation of Thrombin

1976 ◽  
Vol 35 (02) ◽  
pp. 305-313 ◽  
Author(s):  
D.C Triantaphyllopoulos ◽  
L.T Ryan
Keyword(s):  
Factor Viii ◽  
Vitamin K ◽  
Bovine Serum ◽  
Thrombin Generation ◽  
Factor V ◽  
Simultaneous Addition ◽  
Lower Effect

SummaryThe simultaneous addition of suboptimal concentrations of factor VIII and intact or plas-min-lysed fibrinogen into mixtures of the vitamin K dependent factors, phospholipids, adsorbed bovine serum (supplier of factor V) and calcium, increased the amount of thrombin which was generated three to twenty times over the sum of the amounts which were generated when factor VIII, or fibrinogen, or its derivatives were added separately into the thrombin generating mixture. When factor VIII was added together with both fibrinogen and its derivatives, the amount of thrombin generated was even greater, about 130% larger than the amount which was generated in the presence of equal concentrations of only intact fibrinogen plus factor VIII. Addition of albumin instead of fibrinogen or its derivatives has a similar but significantly lower effect on thrombin generation. It appears, therefore, that both intact fibrinogen and its plasminolytic derivatives, singly or in combination, and to a lesser extent albumin, act as cofactors in the reaction which is regulated by factor VIII.

Investigation of the Interaction of Blood Platelets with the Coagulation System at the Site of Plug Formation In Vivo in Man - Effect of Low-Dose Aspirin

1987 ◽  
Vol 57 (01) ◽  
pp. 062-066 ◽  
Author(s):  
P A Kyrle ◽  
J Westwick ◽  
M F Scully ◽  
V V Kakkar ◽  
G P Lewis
Keyword(s):  
Platelet Activation ◽  
Thrombin Generation ◽  
Low Dose ◽  
Bleeding Time ◽  
Blood Platelets ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Plug Formation ◽  
Granule Release

SummaryIn 7 healthy volunteers, formation of thrombin (represented by fibrinopeptide A (FPA) generation, α-granule release (represented by β-thromboglobulin [βTG] release) and the generation of thromboxane B2 (TxB2) were measured in vivo in blood emerging from a template bleeding time incision. At the site of plug formation, considerable platelet activation and thrombin generation were seen within the first minute, as indicated by a 110-fold, 50-fold and 30-fold increase of FPA, TxB2 and PTG over the corresponding plasma values. After a further increase of the markers in the subsequent 3 minutes, they reached a plateau during the fourth and fifth minute. A low-dose aspirin regimen (0.42 mg.kg-1.day-1 for 7 days) caused >90% inhibition of TxB2formation in both bleeding time blood and clotted blood. At the site of plug formation, a-granule release was substantially reduced within the first three minutes and thrombin generation was similarly inhibited. We conclude that (a) marked platelet activation and considerable thrombin generation occur in the early stages.of haemostasis, (b) α-granule release in vivo is partially dependent upon cyclo-oxygenase-controlled mechanisms and (c) thrombin generation at the site of plug formation is promoted by the activation of platelets.

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