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

Streiff, MB, Holmstrom, B, Ashrani, A, Bockenstedt, PL, Chesney, C, Eby, C, Fanikos, J, Fenninger, RB, Fogerty, AE, Gao, S, Goldhaber, SZ, Hendrie, P, Kuderer, N, Lee, A, Lee, JT, Lovrincevic, M, Millenson, MM, Neff, AT, Ortel, TL, Paschal, R, Shattil, S, Siddiqi, T, Smock, KJ, Soff, G, Wang, T-F, Yee, GC, Zakarija, A, McMillian, N, and Engh, AM. "Cancer-Associated Venous Thromboembolic Disease, Version 1.2015." Journal of the National Comprehensive Cancer Network : Jnccn 13, no. 9 (September 2015): 1079-1095.

PMID
26358792
Full Text

Douketis, JD, Spyropoulos, AC, Kaatz, S, Becker, RC, Caprini, JA, Dunn, AS, Garcia, DA, Jacobson, A, Jaffer, AK, Kong, DF, Schulman, S, Turpie, AGG, Hasselblad, V, Ortel, TL, and BRIDGE Investigators, . "Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation." The New England Journal of Medicine 373, no. 9 (August 2015): 823-833.

PMID
26095867
Full Text

Francis, CW, Kessler, CM, Goldhaber, SZ, Kovacs, MJ, Monreal, M, Huisman, MV, Bergqvist, D, Turpie, AG, Ortel, TL, Spyropoulos, AC, Pabinger, I, and Kakkar, AK. "Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study." Journal of Thrombosis and Haemostasis : Jth 13, no. 6 (June 2015): 1028-1035.

PMID
25827941
Full Text

Douketis, J, Spyropoulos, A, Kaatz, S, Caprini, J, Dunn, A, Garcia, D, Jacobson, A, Jaffer, A, Kindzelski, A, Schulman, S, Turpie, AG, Becker, R, Clark, NP, Conti, B, Ellsworth, S, Harrison, RW, Kong, D, Johnson, G, Krishnamoorthy, A, Palmeri, S, Parker, W, Saucedo, J, Schoch, P, Tallman, D, Witt, D, Hasselblad, V, Ortel, TL, and Investigators, BRIDGES. "Bridging anticoagulation in patients who require temporary interruption of warfarin therapy for an elective invasive procedure or surgery (the bridge trial)." June 2015.

Scholars@Duke

Schulman, S, Zondag, M, Linkins, L, Pasca, S, Cheung, YW, de Sancho, M, Gallus, A, Lecumberri, R, Molnar, S, Ageno, W, Le Gal, G, Falanga, A, Hulegårdh, E, Ranta, S, Kamphuisen, P, Debourdeau, P, Rigamonti, V, Ortel, TL, and Lee, A. "Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis." Journal of Thrombosis and Haemostasis : Jth 13, no. 6 (June 2015): 1010-1018.

PMID
25851122
Full Text

Lewis, DA, Suchindran, S, Beckman, MG, Hooper, WC, Grant, AM, Heit, JA, Manco-Johnson, M, Moll, S, Philipp, CS, Kenney, K, De Staercke, C, Pyle, ME, Chi, JT, and Ortel, TL. "Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism." Thrombosis Research 135, no. 4 (April 1, 2015): 659-665.

Full Text

Lewis, DA, Suchindran, S, Beckman, MG, Hooper, WC, Grant, AM, Heit, JA, Manco-Johnson, M, Moll, S, Philipp, CS, Kenney, K, De Staercke, C, Pyle, ME, Chi, J-T, and Ortel, TL. "Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism." Thrombosis research 135, no. 4 (April 2015): 659-665.

PMID
25684211
Full Text

Jiang, W, Boyle, SH, Ortel, TL, Samad, Z, Velazquez, EJ, Harrison, RW, Wilson, J, Kuhn, C, Williams, RB, O'Connor, CM, and Becker, RC. "Platelet aggregation and mental stress induced myocardial ischemia: Results from the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) study." American heart journal 169, no. 4 (April 2015): 496-507.e1.

PMID
25819856
Full Text

Steiner, ME, Ness, PM, Assmann, SF, Triulzi, DJ, Sloan, SR, Delaney, M, Granger, S, Bennett-Guerrero, E, Blajchman, MA, Scavo, V, Carson, JL, Levy, JH, Whitman, G, D'Andrea, P, Pulkrabek, S, Ortel, TL, Bornikova, L, Raife, T, Puca, KE, Kaufman, RM, Nuttall, GA, Young, PP, Youssef, S, Engelman, R, Greilich, PE, Miles, R, Josephson, CD, Bracey, A, Cooke, R, McCullough, J, Hunsaker, R, Uhl, L, McFarland, JG, Park, Y, Cushing, MM, Klodell, CT, Karanam, R, Roberts, PR, Dyke, C, Hod, EA, and Stowell, CP. "Effects of red-cell storage duration on patients undergoing cardiac surgery." The New England Journal of Medicine 372, no. 15 (April 2015): 1419-1429.

PMID
25853746
Full Text

Rabinovich, A, Cohen, JM, Cushman, M, Wells, PS, Rodger, MA, Kovacs, MJ, Anderson, DR, Tagalakis, V, Lazo-Langner, A, 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, Ginsberg, JS, and Kahn, SR. "Inflammation markers and their trajectories after deep vein thrombosis in relation to risk of post-thrombotic syndrome." Journal of thrombosis and haemostasis : JTH 13, no. 3 (March 2015): 398-408.

PMID
25495610
Full Text

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