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Maastricht, Netherlands

Hemker H.C.,Synapse BV
Nederlands tijdschrift voor geneeskunde | Year: 2011

A test is needed of which the score is low in case of haemorrhagic tendency and high in case of thrombotic tendency. Emerging evidence shows that thrombin generation is a promising candidate. Recently it became possible to measure the course in thrombin concentration in clotting blood or blood plasma in an simple way suitable for application in a routine clinical setting. It appears that the amount of thrombin developing in clotting blood or blood plasma is a better measure for thrombotic- or haemorrhagic tendency than any variant of the clotting time and that thrombin generation is a universal test for the effect of antithrombotic drugs.

Scarabin P.-Y.,French Institute of Health and Medical Research | Scarabin P.-Y.,University Paris - Sud | Hemker H.C.,Synapse BV | Clement C.,French Institute of Health and Medical Research | And 4 more authors.
Menopause | Year: 2011

Objective: Increased thrombin generation has emerged as a new surrogate marker of venous thromboembolism. Using calibrated automated thrombography, we tested the influence of the route of estrogen administration and progestogens on thrombin generation among postmenopausal women using hormone therapy. Methods: Baseline thrombin generation, together with clotting factors and inhibitors, was determined in plasma from 115 healthy postmenopausal women. Women were classified by the use of hormone therapy into three groups: nonusers (n = 38), users of oral estrogens (n = 38), and users of transdermal estrogens (n = 39). Results: Oral estrogens dose dependently increased thrombin generation. Thrombin generation was increased among users of transdermal estrogens combined with progestins but was similar to nonusers among women using transdermal estrogens plus progesterone. Prothrombin was the main determinant of thrombin generation and explained a part of these differences. However, single clotting factors and inhibitors contributed little to the hormone-related changes in thrombin generation. Conclusions: Increased thrombin generation can be detected in women using hormone therapy, but this hypercoagulable phenotype depends both on the route of estrogen administration and the type of progestogens. These findings are consistent with current data on the risk of venous thromboembolism related to hormone therapy. © 2011 by The North American Menopause Society.

Devreese K.M.J.,Ghent University | de Laat B.,Maastricht University | de Laat B.,Synapse BV
Journal of Thrombosis and Haemostasis | Year: 2015

Background: According to the ISTH guidelines for lupus anticoagulant (LAC) testing, the second step in the three-step procedure (screening, mixing, and confirmation) is the mixing test, which improves the discrimination between the presence of an inhibitor and coagulation factor deficiencies such as those occurring in patients receiving vitamin K antagonists (VKAs). Objectives: From a retrospective analysis of dilute Russell viper venom (dRVVT) results, we evaluated the impact of the mixing test result on the interpretation of LAC positivity. Methods: We interpreted the dRVVT clotting times with and without taking into account the results of the mixing test in a patient population with prolonged screening test (n = 267) with special attention to the patients receiving VKAs. Results and conclusions: The number of samples classified as 'LAC positive' differed substantially depending on the method of interpretation; 170 and 235 of 267 samples were classified as LAC positive with the three- and two-step procedure, respectively. Discrepancy between the two-step (without mixing step) and the three-step procedure was due to not including a mixing test and was more pronounced in the VKA patient population. Screen/confirm ratios carried out on a 1:1 mix of patient and normal pooled plasma (NPP) gave a lower incidence of 59 of 267. We advise continuing to perform mixing test to avoid false-positives. In patients with discrepant results between the two- and three-step dRVVT interpretation, mainly observed in VKA-treated patients, we advise retesting of the patients preferable beyond the period of anticoagulant therapy and additional testing for anti-beta2GPI and/or anti-cardiolipin antibodies. © 2015 International Society on Thrombosis and Haemostasis.

The present invention relates to the field of blood clotting. Specifically, the invention relates to particular inhibitors of artificial activation of the blood clotting process through contact with foreign surfaces.

A method for the simultaneous measurement of proteolylic enzyme generation and clot strength in plasma or whole blood or any appropriate biological sample derived from blood. The measurement method encompasses the use of a detectable substrate which includes a moiety that can be released upon reaction with the targeted proteolytic enzyme, and elements for measurement of an increase in viscosity of clot strength.

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