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

Vavalle, JP, Rusconi, CP, Zelenkofske, S, Wargin, WA, Ortel, TL, Alexander, JH, Povsic, TJ, and Becker, RC. "The effect of the REG2 Anticoagulation System on thrombin generation kinetics: A pharmacodynamic and pharmacokinetic first-in-human study." Journal of Thrombosis and Thrombolysis 38, no. 3 (January 1, 2014): 275-284.

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Yusuf, HR, Hooper, WC, Beckman, MG, Zhang, QC, Tsai, J, and Ortel, TL. "Risk of venous thromboembolism among hospitalizations of adults with selected autoimmune diseases." Journal of Thrombosis and Thrombolysis 38, no. 3 (January 1, 2014): 306-313.

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Kahn, SR, Shapiro, S, Ducruet, T, Wells, PS, Rodger, MA, Kovacs, MJ, Anderson, D, Tagalakis, V, Morrison, DR, Solymoss, S, Miron, MJ, Yeo, E, Smith, R, Schulman, S, Kassis, J, Kearon, C, Chagnon, I, Wong, T, Demers, C, Hanmiah, R, Kaatz, S, Selby, R, Rathbun, S, Desmarais, S, Opatrny, L, Ortel, TL, Galanaud, JP, and Ginsberg, JS. "Graduated compression stockings to treat acute leg pain associated with proximal DVT: A randomised controlled trial." Thrombosis and Haemostasis 112, no. 6 (January 1, 2014): 1137-1141.

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Kimmel, SE, French, B, Kasner, SE, Johnson, JA, Anderson, JL, Gage, BF, Rosenberg, YD, Eby, CS, Madigan, RA, McBane, RB, Abdel-Rahman, SZ, Stevens, SM, Yale, S, Mohler, ER, Fang, MC, Shah, V, Horenstein, RB, Limdi, NA, Muldowney, JAS, Gujral, J, Delafontaine, P, Desnick, RJ, Ortel, TL, Billett, HH, Pendleton, RC, Geller, NL, Halperin, JL, Goldhaber, SZ, Caldwell, MD, Califf, RM, Ellenberg, JH, and COAG Investigators, . "A pharmacogenetic versus a clinical algorithm for warfarin dosing." The New England Journal of Medicine 369, no. 24 (December 2013): 2283-2293.

PMID
24251361
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Streiff, MB, Bockenstedt, PL, Cataland, SR, Chesney, C, Eby, C, Fanikos, J, Fogerty, AE, Gao, S, Goldhaber, SZ, Hassoun, H, Hendrie, P, Holmstrom, B, Kuderer, N, Lee, JT, Millenson, MM, Neff, AT, Ortel, TL, Siddiqi, T, Smith, JL, Yee, GC, Zakarija, A, McMillian, N, Naganuma, M, and National comprehensive cancer network, . "Venous thromboembolic disease." Journal of the National Comprehensive Cancer Network : Jnccn 11, no. 11 (November 2013): 1402-1429.

PMID
24225973
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Boyle, SH, Samad, Z, Becker, RC, Williams, R, Kuhn, C, Ortel, TL, Kuchibhatla, M, Prybol, K, Rogers, J, O'Connor, C, Velazquez, EJ, and Jiang, W. "Depressive symptoms and mental stress-induced myocardial ischemia in patients with coronary heart disease." Psychosom Med 75, no. 9 (November 2013): 822-831.

PMID
24163385
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Voora, D, Cyr, D, Lucas, J, Chi, J-T, Dungan, J, McCaffrey, TA, Katz, R, Newby, LK, Kraus, WE, Becker, RC, Ortel, TL, and Ginsburg, GS. "Aspirin exposure reveals novel genes associated with platelet function and cardiovascular events." Journal of the American College of Cardiology 62, no. 14 (October 2013): 1267-1276.

PMID
23831034
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Spyropoulos, AC, and Ortel, TL. "Antithrombotic therapy and invasive procedures." N Engl J Med 369, no. 11 (September 12, 2013): 1078-. (Letter)

PMID
24024857
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Adam, SS, McDuffie, JR, Lachiewicz, PF, Ortel, TL, and Williams, JW. "Comparative effectiveness of new oral anticoagulants and standard thromboprophylaxis in patients having total hip or knee replacement: a systematic review." Ann Intern Med 159, no. 4 (August 20, 2013): 275-284. (Review)

PMID
24026260
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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)." Br J Haematol 161, no. 6 (June 2013): 896-898. (Letter)

PMID
23530950
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