Time filter

Source Type

Kretz C.A.,McMaster University | Vaezzadeh N.,McMaster University | Vaezzadeh N.,Thrombosis and Atherosclerosis Research Institute | Gross P.L.,McMaster University | Gross P.L.,University of Michigan
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2010

Mouse models of thrombosis have extended our understanding of the role of tissue factor (TF) in thrombogenesis. Because tissue factor deficiency is embryonic lethal in mice, inventive genetic models are required to probe the role of TF in thrombosis. TF is expressed by different cell types, including vascular smooth muscle cells, cardiomyocytes, fibroblasts, and monocytes. Platelets and endothelial cells also express TF under certain conditions, but the importance of this TF remains controversial. Animal models are commonly used to evaluate the contribution of TF from each cell type to thrombogenesis. Although a variety of well-established injury techniques are used to induce thrombosis, it is likely that the sources of TF that drive thrombosis are model dependent. Therefore, rigorous controls are needed before thrombogenesis can be attributed to TF from a particular cell type. This review summarizes data from mouse models that have attempted to delineate the role of TF in thrombus formation in response to various types of vascular injury. We have consolidated this information to generate unifying concepts that require testing in future studies. © 2010 American Heart Association, Inc. Source

Kelton J.G.,McMaster University | Arnold D.M.,McMaster University | Bates S.M.,McMaster University | Bates S.M.,Thrombosis and Atherosclerosis Research Institute
New England Journal of Medicine | Year: 2013

A 57-year-old man remains in the hospital after experiencing complications from knee-replacement surgery 7 days ago. Low-molecular-weight heparin prophylaxis is initiated on the first postoperative day. Compression ultrasonography performed for left leg swelling noted on day 7 shows a proximal deep-vein thrombosis. A complete blood count reveals that his platelet count has decreased from 300×109 per liter to 125×109 per liter, and an enzyme immunoassay for heparin-induced thrombocytopenia shows a high titer of antibodies against platelet factor 4 (PF4)-heparin complexes. The patient has normal renal function. The physician in the intensive care unit wonders about the best treatment. Copyright © 2013 Massachusetts Medical Society. Source

Majeed A.,Karolinska University Hospital | Schulman S.,Karolinska University Hospital | Schulman S.,McMaster University | Schulman S.,Thrombosis and Atherosclerosis Research Institute
Best Practice and Research: Clinical Haematology | Year: 2013

In the past decade, several new oral anticoagulants (NOACs) have been studied and approved for the prophylaxis and treatment of arterial and venous thromboembolism. These agents were shown to be as effective as or better than warfarin and resulted in comparable or lower bleeding rates than warfarin. Specific antidotes for the reversal of the anticoagulant effect of these drugs, such as monoclonal antibodies against the direct thrombin inhibitor dabigatran or recombinant Xa-analog in the case of factor Xa inhibitors, are still being investigated in early clinical trials. In certain situations, as in case of emergency surgery or life-threatening major bleeding, a rapid reversal strategy is needed. Several non-specific prohemostatic agents or coagulation factor concentrates have been suggested as potential candidates for the reversal of NOACs, but the evidence supporting these agents was mainly derived from small animal studies, or is based on partial or complete correction of laboratory parameters in healthy volunteers treated with these agents. Activated prothrombin complex concentrate seems promising for the reversal of dabigatran, while non-activated prothrombin complex concentrates have potential for the reversal of anti-factor Xa. The risk of thromboembolic complications requires careful evaluation. In this article, the evidence- or the lack of it - supporting the use of the different prohemostatic agents for the management of bleeding and for reversal of the different classes of NOACs is discussed. © 2013 Elsevier Ltd. All rights reserved. Source

Lynn E.G.,McMaster University | Austin R.C.,McMaster University | Austin R.C.,Thrombosis and Atherosclerosis Research Institute
Expert Review of Clinical Pharmacology | Year: 2011

Hydrogen sulfide (H 2S) was the third gaseous transmitter to be discovered, along with nitric oxide and carbon monoxide, and has been proposed to be involved in numerous physiological processes and pathology of various diseases. Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, including atherosclerosis. Atherosclerosis is characterized by multiple key events including endothelial dysfunction, monocyte infiltration and their differentiation into macrophages, conversion of lesion-resident macrophages into foam cells, and smooth muscle cell proliferation. Increasing evidence has indicated that H 2S plays a potentially significant role in all of these biological processes and that malfunction of H 2S homeostasis may contribute to the pathogenesis of atherosclerosis. Experiments have demonstrated that H 2S supplementation ameliorated many of these atherogenic processes and hence, such supplementation potentially may prove to be of therapeutic benefit in the prevention or treatment of atherosclerosis. H 2S levels may be induced by the administration of H 2S or H 2S donors, or alternatively be reduced by the administration of specific cystathionine -synthase or cystathionine -lyase inhibitors. However, issues remain with the potential use of currently available H 2S-modulating agents in a clinical setting. This review will provide a description of the current literature on the involvement of H 2S in these key aspects of vascular biology that contribute to the development of atherosclerosis, as well as the therapeutic potential of currently available H 2S-modulating agents. © 2010 Expert Reviews Ltd. Source

Weitz J.I.,Thrombosis and Atherosclerosis Research Institute
European journal of haematology. Supplementum | Year: 2010

Although parenteral anticoagulants are suitable for short-term indications, oral anticoagulants are preferable for long-term use. Vitamin K antagonists (VKAs) such as warfarin are the only oral anticoagulants currently licensed for long-term use. Although effective, VKAs have multiple limitations that explain, at least in part, their under-use for stroke prevention in patients with atrial fibrillation (AF) and in other indications. Even when they are prescribed, the level of anticoagulation with VKAs is frequently outside the therapeutic range, potentially compromising safety and efficacy. These limitations have prompted development of new oral anticoagulants that target thrombin or Factor Xa. Designed to be given in fixed doses without routine anticoagulation monitoring, these new agents have the potential to revolutionize long-term anticoagulation therapy. Source

Discover hidden collaborations