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

Bertolaccini, ML, Amengual, O, Andreoli, L, Atsumi, T, Chighizola, CB, Forastiero, R, de Groot, P, Lakos, G, Lambert, M, Meroni, P, Ortel, TL, Petri, M, Rahman, A, Roubey, R, Sciascia, S, Snyder, M, Tebo, AE, Tincani, A, and Willis, R. "14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends." Autoimmunity Reviews 13, no. 9 (September 2014): 917-930. (Review)

PMID
24824074
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Bertolaccini, ML, Amengual, O, Andreoli, L, Atsumi, T, Chighizola, CB, Forastiero, R, de Groot, P, Lakos, G, Lambert, M, Meroni, P, Ortel, TL, Petri, M, Rahman, A, Roubey, R, Sciascia, S, Snyder, M, Tebo, AE, Tincani, A, and Willis, R. "14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends." Autoimmunity Reviews 13, no. 9 (September 2014): 917-930.

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McCrindle, BW, Li, JS, Manlhiot, C, Tweddell, JS, Giglia, TM, Massicotte, MP, Monagle, P, Krishnamurthy, R, Mahaffey, KW, Michelson, AD, Verdun, N, Almond, CS, Newburger, JW, Brandão, LR, Esmon, CT, Manco-Johnson, MJ, Ichord, R, Ortel, TL, Chan, AK, Portman, R, Rose, M, Strony, J, and Kaltman, JR. "Challenges and priorities for research: a report from the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH) Working Group on thrombosis in pediatric cardiology and congenital heart disease." Circulation 130, no. 14 (September 2014): 1192-1203.

PMID
25266860
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Ellero-Simatos, S, Lewis, JP, Georgiades, A, Yerges-Armstrong, LM, Beitelshees, AL, Horenstein, RB, Dane, A, Harms, AC, Ramaker, R, Vreeken, RJ, Perry, CG, Zhu, H, Sànchez, CL, Kuhn, C, Ortel, TL, Shuldiner, AR, Hankemeier, T, and Kaddurah-Daouk, R. "Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability." Cpt: Pharmacometrics & Systems Pharmacology 3 (July 16, 2014): e125-null.

PMID
25029353
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Erkan, D, Aguiar, CL, Andrade, D, Cohen, H, Cuadrado, MJ, Danowski, A, Levy, RA, Ortel, TL, Rahman, A, Salmon, JE, Tektonidou, MG, Willis, R, and Lockshin, MD. "14th International Congress on Antiphospholipid Antibodies: task force report on antiphospholipid syndrome treatment trends." Autoimmunity Reviews 13, no. 6 (June 2014): 685-696. (Review)

PMID
24468415
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Devreese, KMJ, Pierangeli, SS, de Laat, B, Tripodi, A, Atsumi, T, Ortel, TL, and Subcommittee on Lupus Anticoagulant/Phospholipid/Dependent Antibodies, . "Testing for antiphospholipid antibodies with solid phase assays: guidance from the SSC of the ISTH." Journal of Thrombosis and Haemostasis : Jth 12, no. 5 (May 2014): 792-795.

PMID
24589091
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Hester, W, Fry, C, Gonzalez, D, Cohen-Wolkowiez, M, Inman, BA, and Ortel, TL. "Thromboprophylaxis with fondaparinux in high-risk postoperative patients with renal insufficiency." Thrombosis research 133, no. 4 (April 2014): 629-633.

PMID
24508189
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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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