Thomas Lee Ortel, MD, PhD

Professor of Medicine
Chief, Division of Hematology in the Department of Medicine
Professor of Pathology
Member of the Duke Cancer Institute
Campus mail 0563 Stead Bldg, Durham, NC 27710
Phone (919) 684-5350
Email address ortel001@mc.duke.edu

My research program investigates the molecular mechanisms whereby various congenital and acquired abnormalities result in ‘dysfunctional’ hemostasis (i.e., hemorrhage or thrombosis) to better understand the molecular mechanisms and interactions that are necessary for normal hemostasis. We are particularly interested in the mechanisms whereby antibodies and other inhibitors can interfere with normal hemostatic mechanisms. Several projects extensively overlap and focus on the assembly and function of procoagulant (e.g., factor X-ase and prothrombinase) and anticoagulant (e.g., activated protein C complex) phospholipid membrane-dependent complexes.

We utilize a variety of approaches in these studies. Monoclonal antibodies, single-chain variable domain fragments, polyclonal antibodies prepared from patients with factor VIII inhibitors, and site-specific mutagenesis have all been used to characterize structure-function relationships in coagulation factor VIII. Our laboratory has also extensively characterized anti-factor V antibodies, investigating autoantibodies as well as xenogenic antibodies developing after exposure to topical bovine thrombin preparations which contain trace amounts of contaminating bovine factor V. We have also characterized how antiphospholipid antibodies interfere with the activated protein C complex, a lipid-dependent natural anticoagulant complex that proteolytically inactivates factor Va and factor VIIIa.

Our current studies are focusing on two antibody-mediated thrombotic syndromes, heparin-induced thrombocytopenia and antiphospholipid antibody syndrome. First, we are initiating a large clinical trial investigating the incidence of clinically-significant heparin-induced thrombocytopenia in patients who develop anti-heparin/platelet factor 4 antibodies following cardiac bypass procedures. While these antibodies are commonly seen following cardiac bypass, the true incidence of thromboembolic complications related to these prothrombotic antibodies remains unknown. We are also collaborating with investigators in the Center for Human Genetics on a large, multi-center study exploring the genetics of familial antiphospholipid antibody syndrome. In addition, we have used a genomic strategy to investigate patients with antiphospholipid antibody syndrome and have identified a gene expression profile that appears to be unique to patients with this syndrome in contrast to patients with venous thromboembolism who do not have these autoantibodies.

We also participate in a variety of collaborative research efforts, both with individual investigators as well as participating in multi-center clinical research studies. For example, we are one of seventeen centers participating in the NIH-supported Transfusion Medicine/Hemostasis Network, and we are currently conducting a trial through this network to define the optimal dose of platelets for patients needing platelet transfusions for hypoproliferative thrombocytopenia. We are also part of a multi-center registry of patients with thrombotic thrombocytopenic purpura, and we are one of eight centers in the Hemostasis and Thrombosis Center pilot program sponsored by the Centers for Disease Control and Prevention. Participation in these registries and networks provides us with access to the patient populations that we study in the research laboratory.

In Their Words

Education and Training

  • Fellow in Hematology-Oncology, Medicineq, Duke University, 1988 - 1991
  • Medical Resident, Medicine, Duke University, 1985 - 1988
  • M.D., Indiana University at Indianapolis, 1985
  • Ph.D., Indiana University at Bloomington, 1983

Publications

Berger, JS, Becker, RC, Kuhn, C, Helms, MJ, Ortel, TL, and Williams, R. "Hyperreactive platelet phenotypes: relationship to altered serotonin transporter number, transport kinetics and intrinsic response to adrenergic co-stimulation." Thromb Haemost 109, no. 1 (January 2013): 85-92.

PMID
23223800
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Piazza, G, Anderson, FA, Ortel, TL, Cox, MJ, Rosenberg, DJ, Rahimian, S, Pendergast, WJ, McLaren, GD, Welker, JA, Akus, JJ, Stevens, SM, Elliott, CG, Freeman, AL, Patton, WF, Dabbagh, O, Wyman, A, Huang, W, Rao, AF, and Goldhaber, SZ. "Randomized trial of physician alerts for thromboprophylaxis after discharge." American Journal of Medicine 126, no. 5 (2013): 435-442.

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Adam, SS, Ortel, TL, and Jr, JWW. "RE: To the editor." Annals of Internal Medicine 158, no. 8 (2013): 637-638.

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Bennett, CL, Jacob, S, Dunn, BL, Georgantopoulos, P, Zheng, XL, Kwaan, HC, Mckoy, JM, Magwood, JS, Qureshi, ZP, Bandarenko, N, Winters, JL, Raife, TJ, Carey, PM, Sarode, R, Kiss, JE, Danielson, C, Ortel, TL, Clark, WF, Ablin, RJ, Rock, G, Matsumoto, M, and Fujimura, Y. "Ticlopidine-associated ADAMTS13 activity deficient thrombotic thrombocytopenic purpura in 22 persons in Japan: A report from the Southern Network on Adverse Reactions (SONAR)." British Journal of Haematology 161, no. 6 (2013): 896-898.

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Spyropoulos, AC, and Ortel, TL. "Antithrombotic therapy and invasive procedures [3]." New England Journal of Medicine 369, no. 11 (2013): 1078--.

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Ortel, TL. "Perioperative management of patients on chronic antithrombotic therapy." Blood 120, no. 24 (December 6, 2012): 4699-4705. (Review)

PMID
22855600
Full Text

Adam, SS, McDuffie, JR, Ortel, TL, and Williams, JW. "Comparative effectiveness of warfarin and new oral anticoagulants for the management of atrial fibrillation and venous thromboembolism: a systematic review." Ann Intern Med 157, no. 11 (December 4, 2012): 796-807. (Review)

PMID
22928173
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Ortel, TL, Kitchens, CS, Erkan, D, Brandão, LR, Hahn, S, James, AH, Kulkarni, R, Manco-Johnson, MJ, Pericak-Vance, M, and Vance, J. "Clinical causes and treatment of the thrombotic storm." Expert review of hematology 5, no. 6 (December 1, 2012): 653-659. (Review)

Scholars@Duke

Chan, MY, Lin, M, Lucas, J, Moseley, A, Thompson, JW, Cyr, D, Ueda, H, Kajikawa, M, Ortel, TL, and Becker, RC. "Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor." Thromb Haemost 108, no. 6 (December 2012): 1180-1191.

PMID
23052711
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Jacob, S, Dunn, BL, Qureshi, ZP, Bandarenko, N, Kwaan, HC, Pandey, DK, McKoy, JM, Barnato, SE, Winters, JL, Cursio, JF, Weiss, I, Raife, TJ, Carey, PM, Sarode, R, Kiss, JE, Danielson, C, Ortel, TL, Clark, WF, Rock, G, Matsumoto, M, Fujimura, Y, Zheng, XL, Chen, H, Chen, F, Armstrong, JM, Raisch, DW, and Bennett, CL. "Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR)." Seminars in Thrombosis and Hemostasis 38, no. 8 (November 2012): 845-853. (Review)

PMID
23111862
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