Dr. Jeffrey Weitz, Director Henderson Research Centre M.D. F.R.C.P.(C), F.A.C.P

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Dr. Weitz is a Professor of Medicine and Biochemistry at McMaster University and Director of the Henderson Research Centre. Board certified in Internal Medicine, Hematology and Medical Oncology, Dr. Weitz now focuses his clinical work in the area of thrombosis. He is the recipient of a Career Investigator Award from the Heart and Stroke Foundation of Canada and holds an Endowed Chair in Cardiovascular Research at McMaster University, which is funded by the Heart and Stroke Foundation of Ontario. He also holds the Canada Research Chair (Tier 1) in Thrombosis. Dr. Weitz received the Medal in Medicine from the Royal College of Physicians and Surgeons of Canada in 1991, the Distinguished Scientist Award from the Heart and Stroke Foundation of Ontario in 1999, the Research Achievement Award from the Canadian Cardiovascular Society in 2006, and the Jack Hirsh Award for Outstanding Academic Achievement, Faculty of Health Sciences, McMaster University in 2008. He is a member of the American Federation of Medical Research, the American Society for Clinical Investigation, and the Association of American Physicians and gave the Davidson Lecture at the University of Edinburgh in 2000 and the Nossel Memorial Lecture at Columbia University in New York in 2003. Dr. Weitz directs a well-funded research laboratory that focuses on the biochemistry of blood coagulation and fibrinolysis as it applies to venous and arterial thrombosis. A former Vice-President of Research for the Heart and Stroke Foundation, member of the Board of Directors of the Heart and Stroke Foundation of Ontario, Chair of the Scientific Review Committee for the Heart and Stroke Foundation of Canada, member of the Executive Council on Thrombosis of the American Heart Foundation, and Chair of the Council on Vascular Biology for the American Society of Hematology, Dr. Weitz has published over 250 peer-reviewed papers and 35 textbook chapters on thrombosis or fibrinolysis.

By focusing on the basic mechanisms by which anticoagulants (blood thinners) and thrombolytic agents (clot digesting drugs) work, Dr. Weitz has opened new avenues of investigation. His demonstration that thrombin bound to fibrin is resistant to inactivation by available anticoagulants stimulated the development of new drugs, some of which are already being used in clinical practice. Through other research, Dr. Weitz has provided an explanation for the puzzling clinical observation that the clot digesting drug, tissue-type plasminogen activator or t-PA, produces more bleeding than was originally anticipated. This work has paved the way for new drugs that may be safer than t-PA.

Dr. Weitz is involved in clinical trials examining optimal methods for prevention, diagnosis and treatment of clotting disorders. He also is an active participant in the education of medical students, residents, and postdoctoral fellows. In addition, he coordinates a graduate course in medical sciences and his laboratory is a fertile training ground for graduate students and postdoctoral fellows in medical sciences and bioengineering.

RECENT PUBLICATIONS (2004-present):

1. Yu JL, May L, Klement P, Weitz JI, Rak J. Oncogenes as regulators of tissue factor expression in cancer: implications for tumor angiogenesis and anti-cancer therapy. Semin Thromb Haemost 30(1):21-30, 2004.

2. Crowther MA, Weitz JI. Ximelagatran: the first oral direct thrombin inhibitor. Expert Opinion on Investigational Drugs 13(4):403-413, 2004.

3. Kearon C, Ginsberg JS, Anderson DR, Kovacs MJ, Wells P, Julian JA, MacKinnon B, Demers C, Douketis J, Turpie AG, vanNguyen P, Green D, Kassis J, Kahn SR, Solymoss S, Desjardins L, Geerts W, Johnston M, Weitz JI, Hirsh J, Gent M,for the SOFAST Investigators. Comparison of one month with three months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor. Journal of Thrombosis and Haemostasis 2(5):743-749, 2004.

4. Young E, Douros V, Podor TJ, Shaughnessy SG, Weitz JI. Localization of heparin and low-molecular-weight heparin in the rat kidney. Thrombosis and Haemostasis 91:927-934, 2004.

5. Wolzt M, Levi M, Sarich TC, Bostrom SL, Eriksson UG, Eriksson-Lepkowska M, Svensson M, Weitz JI, Elg M, Wahlander K. Effect of recombinant factor VIIa on melagatran-induced inhibition of thrombin generation and platelet activation in healthy volunteers. Thrombosis and Haemostasis 91(6):1090-1096, 2004.

6. Weitz JI, Hirsh J, Samama M. New anticoagulant drugs: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126 (Suppl. 3):265S-286S, 2004.

7. Popma JJ, Berger P, Ohman M, Harrington R, Grines C, Weitz J. Antithrombotic therapy during percutaneous coronary intervention: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126 (Suppl. 3):576S-599S, 2004.

8. Weitz JI. New anticoagulants for treatment of venous thromboembolism. Circulation 110(9 Suppl 1):I19-I26, 2004.

9. Weitz JI. Management of venous thromboembolism: present and future (Editorial). Circulation 110(9 Suppl 1): I2, 2004.

10. O’Donnell M, Weitz JI. Novel antithrombotic therapies for the prevention of stroke in patients with atrial fibrillation. American Journal of Managed Care 10 (3 Suppl):S72-S82, 2004.

11. Weitz JI, Middeldorp S, Geerts W, Heit JA. Thrombophilia and new anticoagulant drugs. Hematology (Am Soc Hematol Educ Program);424-438, 2004.

12. Fredenburgh JC, Stafford AR, Pospisil, CH, Weitz JI. Modes and consequences of thrombin’s interaction with fibrin. Biophysical Chemistry 112:277-284, 2004.

13. Liaw PCY, Esmon CT, Kahnamoui K, Schmidt S, Kahnamoui S, Ferrell G, Beaudin S, Julian JA, Weitz JI, Crowther M, Loeb M, Cook D. Patients with severe sepsis vary markedly in their ability to generate activated protein C. Blood 104(13):3958-3964, 2004.

14. Crowther M, Weitz JI. New anticoagulants: An update. Clinical Advances in Hematology and Oncology 2(11):743-749, 2004.

15. Linkins LA, Weitz JI. New anticoagulant therapy. Annual Review of Medicine 56:63-77, 2005.

16. Hirsh J, O’Donnell M, Weitz JI. New anticoagulants. Blood 105(2):453-463, 2005.

17. Yu JL, May L, Lhotak V, Shahrzad S, Shirasawa S, Weitz JI, Coomber BL, Mackman N, Rak JW. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood 105(4):1734-1741, 2005.

18. Vlasin M, Rak J, Weitz JI, Peng L, Gumulec J, Johnston M, Klement P. Heparin compromises streptokinase-induced arterial patency in rabbits. Thrombosis Research 115(4):427-434, 2005.

19. Mehta SR, Steg G, Granger CB, Bassand J-P, Faxon DP, Weitz JI, Afzal R, Rush B, Peters RJG, Natarajan MK, Vellianou JL, Goodhart DM, Labinaz M, Tanguay J-F, Fox KAA, Yusuf S, for the ASPIRE Pilot Investigators. A randomized blinded trial comparing fondaparinux with unfractionated heparin in patients undergoing contemporary percutaneous coronary intervention: The Arixtra Study in Percutaneous Coronary Intervention: A Randomized Evaluation (APSIRE) Pilot Trial. Circulation 111(11):1390-1397, 2005.

20. Bates SM, Weitz JI. New anticoagulants: Beyond heparin, low-molecular-weight heparin, and warfarin. British Journal of Pharmacology 144(8):1017-1028, 2005.

21. O’Donnell M, Weitz JI. Emerging therapies for stroke prevention in atrial fibrillation. European Heart Journal 7;Supplement C:C19-C27, 2005.

22. Weitz JI, Bates SM. New Anticoagulants (ISTH State of the Art Book). Journal of Thrombosis and Haemostasis 3(8):1843-1853, 2005.

23. Yu JY, May L, Lhotak V, Milsom C, Li Y, Shahrzad S, Shirasawa S, Weitz JI, Coomber BL, Micelef J, Guha A, Klement P, Mackman N, Rak JW. Oncogenic events regulating tissue factor expression. Haematologica Reports 1(9):18-20, 2005.

24. Linkins LA, Weitz JI. Pharmacology and clinical potential of direct thrombin inhibitors. Current Pharmaceutical Design 11(30):3877-3884, 2005.

25. Bates SM, Weitz JI. Clinician Update: Coagulation Assays. Circulation 112(4):e53-e60, 2005.

26. Schaefer, AVL, Leslie BA, Rischke JA, Stafford AR, Fredenburgh JC, Weitz JI. Incorporation of fragment X into fibrin clots renders them more susceptible to lysis by plasmin. Biochemistry 45(13):4257-4265, 2006.
27. OASIS-5 Investigators. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. New England Journal of Medicine, 354(14):1464-1476, 2006. (Dr. Weitz is a member of the Steering Committee).

28. OASIS-6 Trial Group. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction – The OASIS-6 Randomized Trial. JAMA 295(13):1519-1530, 2006. (Dr. Weitz is a member of the Steering Committee).

29. Weitz JI. Oral anticoagulants: New vs. old. The Canadian Journal of Diagnosis 23(6):91-95, 2006.

30. Weitz JI. Changing paradigms in the management of venous thromboembolism. American Heart Hospital Journal 4(2):135-141, 2006.

31. Kearon C, Ginsberg JS, Douketis J, Turpie AG, Bates SM, Lee AY, Crowther MA, Weitz
JI, Brill-Edwards P, Wells P, Anderson DR, Kovacs MJ, Linkins LA, Julian JA, Bonilla LR, Gent M, for the Canadian Pulmonary Embolism Diagnosis Study (CANPEDS). An evaluation of D-dimer in the diagnosis of pulmonary embolism: A randomized trial. Annals of Internal Medicine 144:812-821, 2006.

32. Rajgopal R, Butcher M, Weitz JI, Shaughnessy SG. Heparin synergistically enhances interleukin-11 signaling through upregulation of the MAP kinase pathway. Journal of Biological Chemistry, 281(30):20780-20787, 2006.

33. Bates SM, Weitz JI. The status of new anticoagulants. British Journal of Haematology 134(1):3-19, 2006.

34. Weitz JI. Emerging anticoagulants for the treatment of venous thromboembolism. Thrombosis and Haemostasis 96(3):274-284, 2006.

35. Weitz JI. Emerging themes in the treatment of venous thromboembolism (Editorial). Thrombosis and Haemostasis 96(3):239-241, 2006.

36. Becattini C, Agnelli G, Emmerich J, Bura A, Weitz J. Initial treatment of venous thromboembolism. Thrombosis and Haemostasis 96(3):242-250, 2006.

37. Linkins LA, Weitz JI. OASIS-6: Lessons learned (Commentary). Nature Clinical Practice Cardiovascular Medicine 3(9):478-479, 2006.

38. Frank RD, Holscher T, Schabbauer G, Tencati M, Pawlinski R, Weitz JI, Mackman N. A non-anticoagulant synthetic pentasaccharide reduces inflammation in a murine model of kidney ischemia-reperfusion injury. Thrombosis and Haemostasis 96(6):802-806, 2006.

39. Kretz CA, Stafford AR, Fredenburgh JC, Weitz JI. HD1, a thrombin-directed aptamer, binds exosite 1 on prothrombin with high affinity and inhibits its activation by prothrombinase. Journal of Biological Chemistry 281(49):37477-37485, 2006.

40. Linkins LA, Weitz JI. Beyond heparin and warfarin: The new generation of anticoagulants. Expert Opinion on Investigational Drugs 16(3):271-282, 2007.

41. McRae SJ, Stafford AR, Fredenburgh JC, Weitz JI. In the presence of phospholipids, glycosaminoglycans potentiate factor Xa-mediated protein C activation by modulating factor Xa activity. Biochemistry 46(13):4195-4203, 2007.

42. Weitz JI. Emerging anticoagulant drugs. Arteriosclerosis, Thrombosis, and Vascular Biology 27(4):721, 2007.

43. DeCaterina R, Husted S, Wallentin L, Agnelli G, Bachmann F, Baigent C, Jespersen J, Kristensen SD, Montalescot G, Siegbahn A, Verheugt FWA, Weitz JI. Anticoagulants in heart disease: current status and perspectives. European Heart Journal 28(7):880-913, 2007.

44. Eikelboom J, Weitz JI. The replacement for warfarin: The search continues. (Editorial) Circulation 116(2):131-133, 2007.

45. Weitz JI. Factor Xa or thrombin: Is thrombin a better target? (ISTH State of the Art Book). Journal of Thrombosis and Haemostasis 5(Suppl 1):65-68, 2007.

46. Milsom C, Anderson GM, Weitz JI, Rak J. Elevated tissue factor procoagulant activity in CD133-positive cancer cells. Journal of Thrombosis and Haemostasis 5(12):2550-2552, 2007.

47. Milsom C, Yu J, May L, Meehan B, Magnus N, Al-Nedawi K, Luyendyk J, Weitz J, Klement P, Broze G, Mackman N, Rak J. The role of tumor- and host-related tissue factor pools in oncogene-driven tumor progression. Thrombosis Reseearch 120(Suppl 2):S82-S91, 2007.

48. Fredenburgh JC, Stafford AR, Leslie BA, Weitz JI. Bivalent binding to gammaA-gamma' fibrin engages both exosites of thrombin and protects it from inhibition by the antithrombin-heparin complex. Journal of Biological Chemistry 283(5):2470-2477, 2007.

49. Gross PL, Weitz JI. New anticoagulants for treatment of venous thromboembolism. Arteriosclerosis, Thrombosis and Vascular Biology 28(3):380-386, 2008.

50. Bates SM, Weitz JI. Drugs of the Future: Apixaban. Drugs of the Future 33(4):293-301, 2008.

52. Weitz JI, Hirsh J, Samama M. New antithrombotic drugs. Chest 133(6):234S-256S, 2008.

53. Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI. Parenteral anticoagulants: ACCP evidence-based clinical practice guidelines (Eighth Edition). Chest 133(6):141S-159S, 2008.

54. Eikelboom J, Weitz JI. Selective factor Xa inhibition for thromboprophylaxis. The Lancet 372(9632):6-8, 2008.

55. Kearon C, Julian JA, Kovacs MJ, Anderson DR, Wells P, Mackinnon B, Weitz JI, Crowther MA, Dolan S, Turpie AG, Geerts W, Solymoss S, van NGuyen P, Demers C, Kahn SR, Kassis J, Rodger M, Hambleton J, Gent M, Ginsberg JS. Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: Results from a randomized trial. Blood 112(12):4432-4436, 2008.

56. Yee CK, Butcher M, Zeadin M, Weitz JI, Shaughnessy S. Inhibition of osteolytic bone metastasis by unfractionated heparin. Clinical and Experimental Medicine 25(8):903-911, 2008.

57. Yu J, May L, Milsom C, Anderson GM, Weitz JI, Luyendyk JP, Broze G, Mackman N, Rak J. Contribution of host-derived tissue factor to tumor neovascularization. Arteriosclerosis, Thrombosis and Vascular Biology 28(11):1975-1981, 2008.

58. Smyth SS, Woulfe DS, Weitz JI, Gachet C, Conley PB, Goodman SG, Roe MT, Kuliopulos A, Moliterno DJ, French PA, Steinhubl SR, Becker RC, for the 2008 platelet Colloquium Participants. G-Protein-coupled receptors as signaling targets for antiplatelet therapy. Arteriosclerosis, Thrombosis and Vascular Biology. [E-pub ahead of print], November 20, 2008.

59. Jeimy SB, Fuller N, Tasneem S, Segers K, Stafford AR, Weitz JI, Camire RM, Nicolaes GAF, Hayward CPM. Multimerin 1 binds factor V and activated factor V with high affinity and inhibits thrombin generation. Thrombosis and Haemostasis 100(6):1058-1067, 2008.

60. Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of new oral factor IIa and Xa inhibitors in development. Clinical Pharmacokinetics 48(1):1-22, 2009.

61. Eikelboom JE, Weitz JI. Dabigatran etexilate for prevention of venous thromboembolism (Editorial). Thrombosis and Haemostasis 101(1):2-4, 2009.

62. Eikelboom JE, Weitz JI. Anticoagulation for ST-segment elevation myocardial infarction (Editorial). Circulation 119:1186-1188, 2009.

63. Weitz JI. Unanswered questions in venous thromboembolism. Thrombosis Research 123(Supple 4):S2-S10, 2009.

64. ZhouJ, May L, Liao P, Gross PL, Weitz JI. Inferior vena cava ligation rapidly induces tissue factor expression and venous thrombosis in rats. Arteriosclerosis, Thrombosis and Vascular Biology 29:863-869, 2009.

65. Weitz JI. Prevention and treatment of venous thromboembolism during pregnancy. Catheterization and Cardiovascular Interventions 74(Suppl 1):S22-S26, 2009.

66. Gross PL, Weitz JI. New antithrombotic drugs. Clinical Pharmacology and Therapeutics 86(2):139-146, 2009.

67. Chan MY, Weitz JI, Merhi Y, Harrington RA, Becker RC. Catheter thrombosis and percutaneous coronary intervention: Fundamental perspectives on blood, artificial surfaces and antithrombotic drugs. Journal of Thrombosis and Thrombolysis 28(3):366-380, 2009.

68. Eikelboom JW, Weitz JI. Otamixaban in acute coronary syndromes. Lancet 374(9692):762-764, 2009.

69. Petrera NS, Stafford AR, Leslie BA, Kretz CA, Fredenburgh JC, Weitz JI. Long range communications between exosites 1 and 2 modulates thrombin function. Journal of Biological Chemistry July 9, 2009 [E-pub ahead of print].