J I Weitz

Summary

Affiliation: McMaster University
Country: Canada

Publications

  1. ncbi request reprint New anticoagulant drugs
    J I Weitz
    Hamilton Civic Hospitals Research Center and McMaster University, Hamilton, Ontario L8V 1C3, Canada
    J Thromb Thrombolysis 12:7-17. 2001
  2. ncbi request reprint New anticoagulants
    J I Weitz
    Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    J Thromb Haemost 3:1843-53. 2005
  3. doi request reprint New oral anticoagulants in development
    Jeffrey I Weitz
    Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Thromb Haemost 103:62-70. 2010
  4. ncbi request reprint Factor Xa or thrombin: is thrombin a better target?
    J I Weitz
    Henderson Research Centre and McMaster University, Hamilton, ON, Canada
    J Thromb Haemost 5:65-7. 2007
  5. ncbi request reprint Beyond heparin and warfarin: the new generation of anticoagulants
    Jeffrey I Weitz
    McMaster University and Henderson Research Centre, 711 Concession Street, Hamilton, Ontario, L8V 1C3, Canada
    Expert Opin Investig Drugs 16:271-82. 2007
  6. ncbi request reprint Emerging anticoagulants for the treatment of venous thromboembolism
    Jeffrey I Weitz
    Department of Medicine, McMaster University, Hamiton, Ontario, Canada
    Thromb Haemost 96:274-84. 2006
  7. ncbi request reprint Direct thrombin inhibitors in acute coronary syndromes: present and future
    Jeffrey I Weitz
    McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Circulation 105:1004-11. 2002
  8. ncbi request reprint Changing paradigms in the management of venous thromboembolism
    Jeffrey I Weitz
    Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Am Heart Hosp J 4:135-41. 2006
  9. ncbi request reprint Direct thrombin inhibitors
    Jeffrey I Weitz
    McMaster University and Henderson Research Centre, 711 Concession Street, Hamilton, Ontario, Canada, L8V 1C3
    Thromb Res 106:V275-84. 2002
  10. ncbi request reprint New anticoagulant drugs: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
    Jeffrey I Weitz
    Henderson Research Centre, McMaster University, Hamilton, Ontario, Canada
    Chest 126:265S-286S. 2004

Collaborators

Detail Information

Publications102 found, 100 shown here

  1. ncbi request reprint New anticoagulant drugs
    J I Weitz
    Hamilton Civic Hospitals Research Center and McMaster University, Hamilton, Ontario L8V 1C3, Canada
    J Thromb Thrombolysis 12:7-17. 2001
    ..This paper (1) reviews arterial and venous thrombogenesis, (2) outlines new anticoagulant strategies, and (3) provides clinical perspectives on these new strategies...
  2. ncbi request reprint New anticoagulants
    J I Weitz
    Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    J Thromb Haemost 3:1843-53. 2005
    ..After a brief review of coagulation pathways, this paper focuses on new anticoagulants in advanced stages of clinical testing...
  3. doi request reprint New oral anticoagulants in development
    Jeffrey I Weitz
    Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Thromb Haemost 103:62-70. 2010
    ..This paper focuses on the new oral anticoagulants in the most advanced stages of development...
  4. ncbi request reprint Factor Xa or thrombin: is thrombin a better target?
    J I Weitz
    Henderson Research Centre and McMaster University, Hamilton, ON, Canada
    J Thromb Haemost 5:65-7. 2007
    ..Several oral factor Xa inhibitors also are being tested. Is thrombin a better target for new oral anticoagulants than factor Xa? Only time will tell!..
  5. ncbi request reprint Beyond heparin and warfarin: the new generation of anticoagulants
    Jeffrey I Weitz
    McMaster University and Henderson Research Centre, 711 Concession Street, Hamilton, Ontario, L8V 1C3, Canada
    Expert Opin Investig Drugs 16:271-82. 2007
    ....
  6. ncbi request reprint Emerging anticoagulants for the treatment of venous thromboembolism
    Jeffrey I Weitz
    Department of Medicine, McMaster University, Hamiton, Ontario, Canada
    Thromb Haemost 96:274-84. 2006
    ....
  7. ncbi request reprint Direct thrombin inhibitors in acute coronary syndromes: present and future
    Jeffrey I Weitz
    McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Circulation 105:1004-11. 2002
  8. ncbi request reprint Changing paradigms in the management of venous thromboembolism
    Jeffrey I Weitz
    Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Am Heart Hosp J 4:135-41. 2006
  9. ncbi request reprint Direct thrombin inhibitors
    Jeffrey I Weitz
    McMaster University and Henderson Research Centre, 711 Concession Street, Hamilton, Ontario, Canada, L8V 1C3
    Thromb Res 106:V275-84. 2002
    ..This review summarizes the clinical trial data with direct thrombin inhibitors and provides perspective on the role of direct thrombin inhibitors in the face of other new anticoagulants currently under development...
  10. ncbi request reprint New anticoagulant drugs: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
    Jeffrey I Weitz
    Henderson Research Centre, McMaster University, Hamilton, Ontario, Canada
    Chest 126:265S-286S. 2004
    ....
  11. ncbi request reprint New anticoagulants for treatment of venous thromboembolism
    Jeffrey I Weitz
    McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Circulation 110:I19-26. 2004
    ..The lack of an antidote for these new agents is a drawback, particularly for idraparinux, which has a long half-life...
  12. pmc Heparan sulfate: antithrombotic or not?
    Jeffrey I Weitz
    Henderson Research Centre, Hamilton, Ontario, Canada
    J Clin Invest 111:952-4. 2003
  13. ncbi request reprint New anticoagulants: current status and future potential
    Jeffrey I Weitz
    Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Am J Cardiovasc Drugs 3:201-9. 2003
    ....
  14. doi request reprint New antithrombotic drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
    Jeffrey I Weitz
    Henderson Research Center, McMaster University, 711 Concession Street, Hamilton, Ontario, Canada
    Chest 133:234S-256S. 2008
    ....
  15. doi request reprint Prevention and treatment of venous thromboembolism during pregnancy
    Jeffrey I Weitz
    Medicine and Biochemistry, McMaster University, 711 Concession Street, Hamilton, Ontario, Canada
    Catheter Cardiovasc Interv 74:S22-6. 2009
    ..Randomized clinical trials are needed to identify the optimal strategies for prevention and treatment of VTE in pregnancy...
  16. doi request reprint Unanswered questions in venous thromboembolism
    Jeffrey I Weitz
    Departments of Medicine and Biochemistry, McMaster University, Henderson Research Centre, Hamilton, Ontario, Canada
    Thromb Res 123:S2-S10. 2009
    ..In addition, the new agents have the potential to streamline extended VTE therapy because, unlike vitamin K antagonists, they can be given in fixed doses without the need for coagulation monitoring...
  17. ncbi request reprint Vasoflux, a new anticoagulant with a novel mechanism of action
    J I Weitz
    Hamilton Civic Hospitals Reseach Centre, Hamilton, Ontario, Canada
    Circulation 99:682-9. 1999
    ..Heparin does not inactivate fibrin-bound thrombin, whereas hirudin fails to block thrombin generation. In contrast, Vasoflux is a novel anticoagulant that inactivates fibrin-bound thrombin and attenuates factor Xa generation...
  18. ncbi request reprint Beyond heparin and aspirin: new treatments for unstable angina and non-Q-wave myocardial infarction
    J I Weitz
    Department of Medicine, McMaster University, Hamilton Civic Hospital Research Center, Ontario, Canada
    Arch Intern Med 160:749-58. 2000
    ..We focus on the opportunities presented by these agents, detailing mechanisms of action, advantages over aspirin and heparin, and performance in recent clinical trials...
  19. ncbi request reprint Long-term oral anticoagulant therapy in patients with unstable angina or suspected non-Q-wave myocardial infarction: organization to assess strategies for ischemic syndromes (OASIS) pilot study results
    S S Anand
    From the Preventive Cardiology and Therapeutics Program, Hamilton Civics Hospital Research Centre, and Division of Cardiology, McMaster University, Hamilton, Canada
    Circulation 98:1064-70. 1998
    ..We studied the effects of long-term warfarin at 2 intensities in patients with AIS without ST elevation in 2 consecutive randomized controlled studies...
  20. ncbi request reprint Hypersulfated low molecular weight heparin with reduced affinity for antithrombin acts as an anticoagulant by inhibiting intrinsic tenase and prothrombinase
    J A Anderson
    Hamilton Civic Hospitals Research Centre and Department of Medicine, McMaster University, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 276:9755-61. 2001
    ..These studies reveal that sLA-LMWH acts as a potent antithrombin-independent inhibitor of coagulation by attenuating intrinsic tenase and prothrombinase...
  21. ncbi request reprint Heparin compromises streptokinase-induced arterial patency in rabbits
    M Vlasin
    Henderson Research Centre and McMaster University, Hamilton, Ontario, Canada
    Thromb Res 115:427-34. 2005
    ..In this study, we compared the effects of unfractionated heparin (UH), low-molecular weight heparin (LMWH), and recombinant desulfohirudin (HIR) in combination with streptokinase (SK) in such settings...
  22. ncbi request reprint The benefit-to-risk profile of melagatran is superior to that of hirudin in a rabbit arterial thrombosis prevention and bleeding model
    P Klement
    McMaster University and Henderson Research Center, Hamilton, Ontario, Canada
    J Thromb Haemost 1:587-94. 2003
    ..Thus, at maximally effective doses, melagatran causes less bleeding than hirudin in this model. These findings raise the possibility that some direct thrombin inhibitors are safer than others...
  23. ncbi request reprint Molecular basis for the susceptibility of fibrin-bound thrombin to inactivation by heparin cofactor ii in the presence of dermatan sulfate but not heparin
    P C Liaw
    McMaster University and the Henderson Research Centre, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 276:20959-65. 2001
    ..Consequently, thrombin remains susceptible to inactivation by heparin cofactor II. This study explains why fibrin-bound thrombin is susceptible to inactivation by heparin cofactor II in the presence of dermatan sulfate but not heparin...
  24. ncbi request reprint New anticoagulants
    Lori Ann Linkins
    Henderson Research Centre and McMaster University, Hamilton, Ontario, Canada
    Semin Thromb Hemost 29:619-31. 2003
    ....
  25. ncbi request reprint Type 1 plasminogen activator inhibitor binds to fibrin via vitronectin
    T J Podor
    Department of Pathology and Molecular Medicine, McMaster University and the Hamilton Civic Hospitals Research Centre, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 275:19788-94. 2000
    ..These findings indicate that plasma PAI-1.vitronectin complexes can be localized to the surface of fibrin clots; by this localization, they may modulate fibrinolysis and clot reorganization...
  26. ncbi request reprint Clinical utility of a rapid whole-blood D-dimer assay in patients with cancer who present with suspected acute deep venous thrombosis
    A Y Lee
    McMaster University, Hamilton, Ontario, Canada
    Ann Intern Med 131:417-23. 1999
    ..Although D-dimer assays have high negative predictive values for the diagnosis of deep venous thrombosis, their accuracy in patients with cancer is uncertain...
  27. ncbi request reprint Use of a fixed activated partial thromboplastin time ratio to establish a therapeutic range for unfractionated heparin
    S M Bates
    Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    Arch Intern Med 161:385-91. 2001
    ..We sought to identify an aPTT ratio that corresponds to therapeutic anti--factor Xa heparin levels for combinations of several reagents and coagulometers that are commonly used...
  28. ncbi request reprint Prognostic significance of thrombocytopenia during hirudin and heparin therapy in acute coronary syndrome without ST elevation: Organization to Assess Strategies for Ischemic Syndromes (OASIS-2)study
    J W Eikelboom
    Preventive Cardiology and Therapeutics Program, McMaster University, Hamilton, Canada
    Circulation 103:643-50. 2001
    ..The excess of major bleeding in hirudin-treated patients who develop thrombocytopenia suggests that thrombocytopenia may contribute to the increased risk of bleeding observed with hirudin...
  29. doi request reprint Update on heparin: what do we need to know?
    Daniel S Weitz
    Department of Medicine, McMaster University, and Henderson Research Centre, Hamilton, ON, Canada
    J Thromb Thrombolysis 29:199-207. 2010
    ....
  30. ncbi request reprint The status of new anticoagulants
    Shannon M Bates
    Department of Medicine, McMaster University, ON, Canada
    Br J Haematol 134:3-19. 2006
    ..This paper reviews the pharmacology of these new agents and describes the results of clinical trials with new anticoagulants in more advanced stages of clinical testing...
  31. ncbi request reprint Direct thrombin inhibitors in cardiac disease
    Jeffrey I Weitz
    McMaster University, Hamilton, Ontario, Canada
    Cardiovasc Toxicol 3:13-25. 2003
    ..Additionally, bivalirudin also appears to provide clinical advantages over unfractionated heparin therapy in ACS patients and those undergoing percutaneous coronary intervention...
  32. doi request reprint New antithrombotic drugs
    P L Gross
    Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Clin Pharmacol Ther 86:139-46. 2009
    ..This paper focuses on these new targets and new antiplatelet drugs and anticoagulants and describes the major advances in the continuing search for more potent antithrombotic drugs that have limited effects on hemostasis...
  33. ncbi request reprint Fibrinolytic variables in patients with recurrent venous thrombosis: a prospective cohort study
    M A Crowther
    Hamilton Civic Hospitals Research Centre, Henderson General Hospital, ON, Canada
    Thromb Haemost 85:390-4. 2001
    ..Our study also confirms that patients with idiopathic venous thromboembolism have a high risk of recurrence...
  34. ncbi request reprint Conformational changes in thrombin when complexed by serpins
    J C Fredenburgh
    Hamilton Civic Hospitals Research Centre and Department of Medicine, McMaster University, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 276:44828-34. 2001
    ..The disorganization of exosite 1 that occurs when thrombin is complexed by serpins is consistent with results of protease sensitivity studies and crystallographic analysis of a homologous enzyme-serpin complex...
  35. ncbi request reprint Like fibrin, (DD)E, the major degradation product of crosslinked fibrin, protects plasmin from inhibition by alpha2-antiplasmin
    A Y Lee
    Department of Medicine, McMaster University and Hamilton Civic Hospitals Research Centre, Ontario, Canada
    Thromb Haemost 85:502-8. 2001
    ..This provides a mechanism to limit the concentration of (DD)E and maintain the fibrin-specificity of t-PA...
  36. ncbi request reprint Management of suspected deep venous thrombosis in outpatients by using clinical assessment and D-dimer testing
    C Kearon
    McMaster University Clinic, Room 401, Henderson General Hospital, 711 Concession Street; Hamilton, Ontario L8V 1C3, Canada
    Ann Intern Med 135:108-11. 2001
    ..9% to 100%]). CONCLUSION: The combination of a low pretest probability of deep venous thrombosis and a negative result on a whole-blood D -dimer test rules out deep venous thrombosis in a large proportion of symptomatic outpatients...
  37. ncbi request reprint Thrombin binds to soluble fibrin degradation products where it is protected from inhibition by heparin-antithrombin but susceptible to inactivation by antithrombin-independent inhibitors
    J I Weitz
    Department of Medicine, McMaster University and Hamilton Civic Hospitals Research Centre, Ontario, Canada
    Circulation 97:544-52. 1998
    ..Thrombolytic therapy induces a procoagulant state characterized by elevated plasma levels of fibrinopeptide A (FPA), but the responsible mechanism is uncertain...
  38. doi request reprint Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation
    Jeffrey I Weitz
    Thrombosis and Atherosclerosis Research Institute, Hamilton General Hospital, Ontario, Canada
    Thromb Haemost 104:633-41. 2010
    ..In contrast, the edoxaban bid regimens were associated with more bleeding than warfarin. These results suggest that in this three-month study, edoxaban 30 or 60 mg qd are safe and well-tolerated...
  39. doi request reprint Meeting the unmet needs in anticoagulant therapy
    Jeffrey I Weitz
    Thrombosis and Atherosclerosis Research Institute, Hamilton General Hospital, Hamilton, ON, Canada
    Eur J Haematol 85:p1-28. 2010
    ..Designed to be given in fixed doses without routine anticoagulation monitoring, these new agents have the potential to revolutionize long-term anticoagulation therapy...
  40. doi request reprint HD1, a thrombin- and prothrombin-binding DNA aptamer, inhibits thrombin generation by attenuating prothrombin activation and thrombin feedback reactions
    Colin A Kretz
    Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Thromb Haemost 103:83-93. 2010
    ..These findings identify prothrombin as a potential target for new anticoagulants...
  41. ncbi request reprint Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor
    C Kearon
    McMaster University, Hamilton, Ontario, Canada
    J Thromb Haemost 2:743-9. 2004
    ..Retrospective analyses suggest that 1 month of anticoagulation is adequate for patients whose venous thromboembolic event was provoked by a transient risk factor...
  42. doi request reprint Leukocyte urokinase plasminogen activator receptor and PSGL1 play a role in endogenous arterial fibrinolysis
    Xufang Bai
    Henderson Research Centre and McMaster University, Hamilton, Ontario, Canada
    Thromb Haemost 102:1212-8. 2009
    ..Thus, fibrin loss from microarteriolar thrombi is mediated, at least in part, by leukocyte-associated uPA in a process that requires leukocyte uPAR and PSGL-1...
  43. ncbi request reprint In the presence of phospholipids, glycosaminoglycans potentiate factor Xa-mediated protein C activation by modulating factor Xa activity
    Simon J McRae
    Department of Medicine, McMaster University, 1280 Main Street West, Hamilton Ontario L8S 4L8, Canada
    Biochemistry 46:4195-203. 2007
    ..Xa. This study reveals that when f.Xa interacts with anionic phospholipids, glycosaminoglycans bind f.Xa more tightly, allosterically modulate its active site, and enhance its capacity to activate protein C...
  44. doi request reprint New anticoagulants for treatment of venous thromboembolism
    Peter L Gross
    Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    Arterioscler Thromb Vasc Biol 28:380-6. 2008
    ....
  45. ncbi request reprint Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism
    Clive Kearon
    McMaster University, Hamilton, Ont
    N Engl J Med 349:631-9. 2003
    ..After three months of conventional warfarin therapy, a lower dose of anticoagulant medication may result in less bleeding and still prevent recurrent venous thromboembolism...
  46. ncbi request reprint Glycosaminoglycans bind factor Xa in a Ca2+-dependent fashion and modulate its catalytic activity
    Lee A O'Brien
    Henderson Research Centre and McMaster University, Hamilton, Ontario L8V 1C3, Canada
    Biochemistry 42:13091-8. 2003
    ..These studies suggest that glycosaminoglycan binding perturbs exosites on the surface of factor Xa, potentially modifying interactions with cofactors or substrates...
  47. ncbi request reprint Acute coronary syndromes: a focus on thrombin
    Jeffrey I Weitz
    Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    J Invasive Cardiol 14:2B-7B. 2002
  48. doi request reprint Inferior vena cava ligation rapidly induces tissue factor expression and venous thrombosis in rats
    Ji Zhou
    Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    Arterioscler Thromb Vasc Biol 29:863-9. 2009
    ..Although stasis is important in the pathogenesis of deep vein thrombosis (DVT), how it contributes to thrombogenesis is largely unknown. To gain mechanistic insight, we used a rat model of inferior vena cava (IVC) ligation...
  49. pmc New anticoagulants: beyond heparin, low-molecular-weight heparin and warfarin
    Shannon M Bates
    Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Br J Pharmacol 144:1017-28. 2005
    ..After a brief review of thrombogenesis and its regulation, this paper focuses on new anticoagulant agents in more advanced stages of clinical testing...
  50. ncbi request reprint HD1, a thrombin-directed aptamer, binds exosite 1 on prothrombin with high affinity and inhibits its activation by prothrombinase
    Colin A Kretz
    Department of Medicine, McMaster University, and Henderson Research Centre, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 281:37477-85. 2006
    ..These findings suggest that exosite 1 on prothrombin exists as a proexosite only for ligands whose primary target is thrombin rather than prothrombin...
  51. ncbi request reprint Coagulation assays
    Shannon M Bates
    Department of Medicine, McMaster University, Henderson Research Centre, Hamilton, Ontario, Canada
    Circulation 112:e53-60. 2005
  52. ncbi request reprint Identification of Dp71 isoforms in the platelet membrane cytoskeleton. Potential role in thrombin-mediated platelet adhesion
    Richard C Austin
    Department of Pathology, McMaster University and the Henderson Research Centre, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 277:47106-13. 2002
    ..Collectively, our results provide evidence that Dp71Delta(110) is a component of the platelet membrane cytoskeleton, is involved in cytoskeletal reorganization and/or signaling, and plays a role in thrombin-mediated platelet adhesion...
  53. ncbi request reprint New anticoagulants: an update
    Mark Crowther
    Division of Hematology, St Joseph s Hospital, McMaster University, Hamilton, Ontario, Canada
    Clin Adv Hematol Oncol 2:743-9. 2004
    ....
  54. ncbi request reprint Bivalent binding to gammaA/gamma'-fibrin engages both exosites of thrombin and protects it from inhibition by the antithrombin-heparin complex
    James C Fredenburgh
    Henderson Research Centre and McMaster University, Hamilton, Ontario, Canada
    J Biol Chem 283:2470-7. 2008
    ..Thus, bivalent binding of thrombin to gamma(A)/gamma'-fibrin protects thrombin from inhibition, raising the possibility that gamma(A)/gamma'-fibrin serves as a reservoir of active thrombin that renders thrombi thrombogenic...
  55. doi request reprint Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
    Jack Hirsh
    Henderson Research Centre, Hamilton Civic Hospitals, 711 Concession Street, Hamilton, Ontario, Canada
    Chest 133:141S-159S. 2008
    ..Three parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in HIT patients...
  56. ncbi request reprint Vimentin exposed on activated platelets and platelet microparticles localizes vitronectin and plasminogen activator inhibitor complexes on their surface
    Thomas J Podor
    Department of Pathology and Molecular Medicine, McMaster University and the Hamilton Civic Hospitals Research Centre, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 277:7529-39. 2002
    ..These findings suggest that platelet vimentin may regulate fibrinolysis in plasma and thrombi by binding platelet-derived Vn.PAI-1 complexes...
  57. ncbi request reprint New anticoagulant therapy
    Lori Ann Linkins
    McMaster University and Henderson Research Center, Hamilton, Ontario, Canada L8V 1C3
    Annu Rev Med 56:63-77. 2005
    ..This review identifies the molecular targets of new anticoagulants, describes the results of clinical trials, and provides clinical perspective on the opportunities for new anticoagulants...
  58. ncbi request reprint Multimerin 1 binds factor V and activated factor V with high affinity and inhibits thrombin generation
    Samira B Jeimy
    Department of Pathology and Molecular Medicine, Health Sciences Center, McMaster University, 1200 Main St West, Hamilton, Ontario, Canada, L8N 3Z5
    Thromb Haemost 100:1058-67. 2008
    ..The high affinity binding of FV to MMRN1 may facilitate the costorage of the two proteins in platelet alpha-granules. As a consequence, MMRN1 release during platelet activation may limit platelet dependent thrombin generation in vivo...
  59. ncbi request reprint New anticoagulants
    Jack Hirsh
    Henderson Research Center, and McMaster University, Hamilton, Ontario, Canada
    Blood 105:453-63. 2005
    ..Large phase 3 trials evaluating ximelagatran for the secondary prevention of venous thromboembolism and prevention of cardioembolic events in patients with atrial fibrillation have been completed...
  60. ncbi request reprint Patients with severe sepsis vary markedly in their ability to generate activated protein C
    Patricia C Y Liaw
    Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    Blood 104:3958-64. 2004
    ..Baseline APC levels were higher in survivors (P = .024), and baseline F1 + 2/APC ratios were lower in survivors (P = .047). Larger studies are warranted to establish whether APC generation profiles aid in managing sepsis...
  61. pmc Thromboprophylaxis in surgical patients
    Martin O'Donnell
    Henderson Research Centre, McMaster University, Hamilton, Ont
    Can J Surg 46:129-35. 2003
    ..Low-molecular-weight heparin (LMWH) or warfarin is the choice for patients with spinal cord operations and all patients with major trauma who do not have contraindications to anticoagulation should receive thromboprophylaxis with LMWH...
  62. ncbi request reprint Randomized, blinded trial comparing fondaparinux with unfractionated heparin in patients undergoing contemporary percutaneous coronary intervention: Arixtra Study in Percutaneous Coronary Intervention: a Randomized Evaluation (ASPIRE) Pilot Trial
    Shamir R Mehta
    McMaster University and the Population Health Research Institute, Hamilton Health Sciences, General Division, 237 Barton St E, Hamilton, Ontario, Canada L6K 1B8
    Circulation 111:1390-7. 2005
    ..We performed a randomized trial to determine the safety and feasibility of fondaparinux in the percutaneous coronary intervention (PCI) setting...
  63. ncbi request reprint Ximelagatran: the first oral direct thrombin inhibitor
    Mark A Crowther
    McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Expert Opin Investig Drugs 13:403-13. 2004
    ..It will also review the pharmacology of ximelagatran, discuss the clinical trial results with ximelagatran and provide perspective on the advantages and potential limitations of ximelagatran...
  64. ncbi request reprint Mechanism of catalysis of inhibition of factor IXa by antithrombin in the presence of heparin or pentasaccharide
    Ericka M Wiebe
    Henderson Research Centre and McMaster University, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 278:35767-74. 2003
    ..IXa. Furthermore, our data suggest that the efficacy of pentasaccharide for prevention and treatment of thrombotic disorders may reflect its action at two sites in the coagulation system...
  65. ncbi request reprint Incorporation of vitronectin into fibrin clots. Evidence for a binding interaction between vitronectin and gamma A/gamma' fibrinogen
    Thomas J Podor
    Department of Pathology and Molecular Medicine, McMaster University and the Hamilton Civic Hospitals Research Centre, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 277:7520-8. 2002
    ..These studies reveal that vitronectin associates with fibrin during coagulation, and may thereby modulate hemostasis and inflammation...
  66. ncbi request reprint Mechanisms responsible for catalysis of the inhibition of factor Xa or thrombin by antithrombin using a covalent antithrombin-heparin complex
    Nethnapha Paredes
    Henderson Research Centre, Hamilton, Ontario L8V 1C3
    J Biol Chem 278:23398-409. 2003
    ..These data may suggest that access to pentasaccharide units in non-covalent AT.H complexes by free AT may be facile...
  67. ncbi request reprint Incorporation of fragment X into fibrin clots renders them more susceptible to lysis by plasmin
    Amy V L Schaefer
    Department of Medicine, McMaster University, Hamilton, Ontario L8V 1C3, Canada
    Biochemistry 45:4257-65. 2006
    ..These data suggest that structural changes resulting from incorporation of fragment X into clots promote their lysis. Thus, attenuation of thrombolytic therapy-induced fragment X formation may reduce the risk of bleeding...
  68. pmc Long range communication between exosites 1 and 2 modulates thrombin function
    Nicolas S Petrera
    Department of Medicine, McMaster University, and Henderson Research Center, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 284:25620-9. 2009
    ..These findings provide evidence for long range allosteric linkage between exosites 1 and 2 on thrombin, revealing further complexity to the mechanisms of thrombin regulation...
  69. ncbi request reprint Evidence that both exosites on thrombin participate in its high affinity interaction with fibrin
    Caroline H Pospisil
    Department of Medicine, McMaster University and the Henderson Research Centre, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 278:21584-91. 2003
    ....
  70. ncbi request reprint In vitro comparison of the effect of heparin, enoxaparin and fondaparinux on tests of coagulation
    Lori Ann Linkins
    Henderson Research Centre and McMaster University, 711 Concession Street, Hamilton, Ontario, Canada L8V 1C3
    Thromb Res 107:241-4. 2002
    ..The ACT and aPTT therefore cannot be used to monitor low-molecular weight heparin or fondaparinux, highlighting the need for a point-of-care anti-factor Xa assay...
  71. doi request reprint Potential of new anticoagulants in patients with cancer
    Jeffrey I Weitz
    Departments of Medicine and Biochemistry and Biomedical Sciences, McMaster University and Henderson Research Centre, Ontario, Canada
    Thromb Res 125:S30-5. 2010
    ..In the coming years, these drugs are likely to replace warfarin for most indications. This paper addresses their potential role for prevention and treatment of cancer-related thrombosis...
  72. ncbi request reprint Novel antithrombotic therapies for the prevention of stroke in patients with atrial fibrillation
    Martin O'Donnell
    Henderson Research Centre, McMaster University, Hamilton, Ontario, Canada
    Am J Manag Care 10:S72-82. 2004
    ....
  73. doi request reprint Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial
    Clive Kearon
    McMaster University, Hamilton, ON
    Blood 112:4432-6. 2008
    ..7; 95% CI, 0.2-2.3) or more than one (HR, 0.7; 95% CI, 0.2-3.4) defect. We conclude that single or multiple thrombophilic defects are not associated with a higher risk of recurrent VTE during warfarin therapy...
  74. ncbi request reprint Antithrombin-independent anticoagulation by hypersulfated low-molecular-weight heparin
    James C Fredenburgh
    Henderson Research Centre, Hamilton, Ontario, Canada
    Trends Cardiovasc Med 12:281-7. 2002
    ..In a rabbit carotid artery thrombosis prevention model, sLA-LMWH is superior to LMWH. Because of its low affinity for antithrombin and multiple sites of action, sLA-LMWH may prove to be safer and more effective than other anticoagulants...
  75. ncbi request reprint Heparin synergistically enhances interleukin-11 signaling through up-regulation of the MAPK pathway
    Raghav Rajgopal
    Department of Pathology, McMaster University and the Henderson Research Centre, Hamilton, Ontario, Canada
    J Biol Chem 281:20780-7. 2006
    ....
  76. doi request reprint Zinc: an important cofactor in haemostasis and thrombosis
    Trang T Vu
    Thrombosis and Atherosclerosis Research Institute, Department of Medical Sciences, McMaster University, 237 Barton St E, Hamilton, Ontario L8L 2X2, Canada
    Thromb Haemost 109:421-30. 2013
    ..This paper reviews the mechanisms by which zinc regulates coagulation, platelet aggregation, anticoagulation and fibrinolysis and outlines how zinc serves as a ubiquitous modulator of haemostasis and thrombosis...
  77. ncbi request reprint A Protease TAMER: a nucleic acid-based anticoagulant
    J C Fredenburgh
    Departments of Medicine and Biochemistry and Biomedical Sciences and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada
    J Thromb Haemost 10:867-9. 2012
    ..See also Bompiani KM, Monroe DM, Church FC, Sullenger BA. A high affinity, antidote-controllable prothrombin and thrombin-binding RNA aptamer inhibits thrombin generation and thrombin activity. This issue, pp 870-80...
  78. ncbi request reprint Homocysteine-dependent alterations in mitochondrial gene expression, function and structure. Homocysteine and H2O2 act synergistically to enhance mitochondrial damage
    R C Austin
    Hamilton Civic Hospitals Research Centre and McMaster University, Hamilton, Ontario L8V 1C3, Canada
    J Biol Chem 273:30808-17. 1998
    ..Furthermore, our findings suggest that intracellular glutathione and heat shock proteins play a role in protecting mitochondria against the adverse effects elicited by homocysteine and H2O2...
  79. doi request reprint Inhibition of osteolytic bone metastasis by unfractionated heparin
    Colin K Yee
    Department of Pathology and Molecular Medicine, McMaster University and the Henderson Research Center, 711 Concession Street, Hamilton, Ontario, Canada, L8V 1C3
    Clin Exp Metastasis 25:903-11. 2008
    ..Based on these observations, we conclude that heparin inhibits the ability of tumour cells to metastasize to bone and that as such, prevents tumour cell-induced decreases in bone strength...
  80. pmc Binding of anti-GRP78 autoantibodies to cell surface GRP78 increases tissue factor procoagulant activity via the release of calcium from endoplasmic reticulum stores
    Ali A Al-Hashimi
    Department of Medicine and Division of Nephrology, St Joseph s Hospital and McMaster University, Hamilton, Ontario L8N 4A6, Canada
    J Biol Chem 285:28912-23. 2010
    ..Furthermore, blocking GRP78 signaling on the surface of cancer cells attenuates TF PCA and has the potential to reduce the risk of cancer-related venous thromboembolism...
  81. ncbi request reprint A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis
    Shannon M Bates
    McMaster University Medical Centre, HSC 3W11, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada
    Ann Intern Med 138:787-94. 2003
    ..Because clinical diagnosis is inaccurate, objective testing is usually considered necessary when patients present with suspected deep venous thrombosis (DVT)...
  82. ncbi request reprint An update on new anticoagulants
    Lori Ann Linkins
    McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada L8V 1C3
    Curr Drug Targets Cardiovasc Haematol Disord 3:287-300. 2003
    ....
  83. ncbi request reprint Pharmacology and clinical potential of direct thrombin inhibitors
    Lori Ann Linkins
    McMaster University and Henderson Research Centre, Hamilton, Ontario, L8V 1C3, Canada
    Curr Pharm Des 11:3877-84. 2005
    ....
  84. ncbi request reprint A novel approach to thrombin inhibition
    Jeffrey I Weitz
    Henderson Research Centre, and McMaster University, Hamilton, Ontario, Canada
    Thromb Res 109:S17-22. 2003
    ..Large-scale clinical trials are under way to evaluate the utility of an orally active prodrug form of melagatran for prevention and treatment of venous and arterial thrombosis...
  85. pmc Contribution of host-derived tissue factor to tumor neovascularization
    Joanne Yu
    Henderson Research Centre, McMaster University, Hamilton, ON, Canada
    Arterioscler Thromb Vasc Biol 28:1975-81. 2008
    ..The role of host-derived tissue factor (TF) in tumor growth, angiogenesis, and metastasis has hitherto been unclear and was investigated in this study...
  86. doi request reprint Selective factor Xa inhibition for thromboprophylaxis
    John W Eikelboom
    McMaster University, Hamilton, ON, Canada
    Lancet 372:6-8. 2008
  87. ncbi request reprint Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells
    P A Outinen
    Department of Pathology and Molecular Medicine, McMaster University and the Hamilton Civic Hospitals Research Centre, Hamilton, Ontario, Canada
    Blood 94:959-67. 1999
    ....
  88. ncbi request reprint Management of venous thromboembolism: present and future
    Jeffrey I Weitz
    McMaster University
    Circulation 110:I2. 2004
  89. ncbi request reprint A replacement for warfarin: the search continues
    John W Eikelboom
    Circulation 116:131-3. 2007
  90. ncbi request reprint A non-anticoagulant synthetic pentasaccharide reduces inflammation in a murine model of kidney ischemia-reperfusion injury
    Rolf Dario Frank
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Thromb Haemost 96:802-6. 2006
    ..These findings indicate that the anti-inflammatory activity of fondaparinux can be dissociated from its anticoagulant activity and that NAC-pentasaccharide is protective in kidney I/R injury...
  91. ncbi request reprint Initial treatment of venous thromboembolism
    Cecilia Becattini
    Division of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Italy
    Thromb Haemost 96:242-50. 2006
    ..An oral anticoagulant agent to be used without laboratory monitoring for both acute and long-term treatment of VTE remains an unsolved clinical need in the treatment of VTE...
  92. ncbi request reprint Life-threatening thrombosis in mice with targeted Arg48-to-Cys mutation of the heparin-binding domain of antithrombin
    Mieke Dewerchin
    Center for Transgene Technology and Gene Therapy, VIB, KULeuven Campus Gasthuisberg O and N, Herestraat 49, B 3000 Leuven, Belgium
    Circ Res 93:1120-6. 2003
    ....
  93. ncbi request reprint Heparin and angiogenesis: size matters!
    Janusz Rak
    Arterioscler Thromb Vasc Biol 23:1954-5. 2003
  94. ncbi request reprint Emerging themes in the treatment of venous thromboembolism
    Jeffrey I Weitz
    Thromb Haemost 96:239-41. 2006
  95. pmc The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kappaB and mitogen-activated protein kinase pathways
    Edward M Conway
    The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, B 3000 Leuven, Belgium
    J Exp Med 196:565-77. 2002
    ..These data suggest that TM has antiinflammatory properties in addition to its role in coagulation and fibrinolysis...
  96. ncbi request reprint Effect of recombinant factor VIIa on melagatran-induced inhibition of thrombin generation and platelet activation in healthy volunteers
    Michael Wolzt
    Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, Vienna, Austria
    Thromb Haemost 91:1090-6. 2004
    ..However, the potential value of higher, continuous or repeated doses of rFVIIa or its use with lower melagatran concentrations has not been excluded...
  97. ncbi request reprint Evaluation of DNA aptamers directed to thrombin as potential thrombus imaging agents
    Hayes Dougan
    TRIUMF, Vancouver, BC, V6T 2A3, Canada
    Nucl Med Biol 30:61-72. 2003
    ....
  98. ncbi request reprint Antithrombotic therapy during percutaneous coronary intervention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
    Jeffrey J Popma
    Interventional Cardiology, Brigham and Women s Hospital, 75 Francis St, Tower 2 3A Room 311, Boston, MA 02115, USA
    Chest 126:576S-599S. 2004
    ..In patients who undergo PCI with no other indication for systemic anticoagulation therapy, we recommend against routine use of vitamin K antagonists after PCI (Grade 1A)...
  99. ncbi request reprint Modes and consequences of thrombin's interaction with fibrin
    James C Fredenburgh
    Henderson Research Centre and McMaster University, 711 Concession St, Hamilton Ontario, Canada L8V 1C3
    Biophys Chem 112:277-84. 2004
    ..The mechanisms by which thrombin binds fibrin are reviewed in this paper. As well, the potential pathological consequences of thrombin's interaction with fibrin are discussed...
  100. ncbi request reprint Localization of heparin and low-molecular-weight heparin in the rat kidney
    Edward Young
    Department of Pathology, McMaster University, Henderson Research Centre, Hamilton, Ontario, Canada, L8V 1C3
    Thromb Haemost 91:927-34. 2004
    ..These findings suggest that renal excretion of UFH and LMWH primarily reflects tubular uptake via an organic anion transport mechanism...
  101. ncbi request reprint Emerging anticoagulant drugs
    Shannon M Bates
    Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    Arterioscler Thromb Vasc Biol 23:1491-500. 2003
    ..After a brief review of thrombogenesis and its regulation, this study focuses on new anticoagulant agents in more advanced stages of clinical testing...