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

Grants

Publications

Doherty, John U., Ty J. Gluckman, William J. Hucker, James L. Januzzi, Thomas L. Ortel, Sherry J. Saxonhouse, and Sarah A. Spinler. “2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients With Nonvalvular Atrial Fibrillation: A Report of the American College of Cardiology Clinical Expert Consensus Document Task Force.” J Am Coll Cardiol 69, no. 7 (February 21, 2017): 871–98. https://doi.org/10.1016/j.jacc.2016.11.024.

PMID
28081965
Full Text

Feigal, Jacob P., Stephen H. Boyle, Zainab Samad, Eric J. Velazquez, Jennifer L. Wilson, Richard C. Becker, Redford B. Williams, et al. “Associations between positive emotional well-being and stress-induced myocardial ischemia: Well-being scores predict exercise-induced ischemia.” J Psychosom Res 93 (February 2017): 14–18. https://doi.org/10.1016/j.jpsychores.2016.11.012.

PMID
28107887
Full Text

Welsby, I. J., E. F. Krakow, J. A. Heit, E. C. Williams, G. M. Arepally, S. Bar-Yosef, D. F. Kong, et al. “The association of anti-platelet factor 4/heparin antibodies with early and delayed thromboembolism after cardiac surgery.” J Thromb Haemost 15, no. 1 (January 2017): 57–65. https://doi.org/10.1111/jth.13533.

PMID
27714919
Full Text

Komforti, Miglena K., Elizabeth S. Bressler, Maria A. Selim, Garrett S. Bressler, and Thomas L. Ortel. “A rare cutaneous manifestation of hemorrhagic bullae to low-molecular-weight heparin and fondaparinux: report of two cases.” J Cutan Pathol 44, no. 1 (January 2017): 104–6. https://doi.org/10.1111/cup.12821.

PMID
27766660
Full Text

Klinger, Rebecca Y., Mary Cooter, Miles Berger, Mihai V. Podgoreanu, Mark Stafford-Smith, Thomas L. Ortel, Ian J. Welsby, et al. “Effect of intravenous lidocaine on the transcerebral inflammatory response during cardiac surgery: a randomized-controlled trial.” Can J Anaesth 63, no. 11 (November 2016): 1223–32. https://doi.org/10.1007/s12630-016-0704-0.

PMID
27470233
Full Text

Krishnamoorthy, Arun, and Thomas Ortel. “A Bridge to Nowhere? Benefits and Risks for Periprocedural Anticoagulation in Atrial Fibrillation.” Curr Cardiol Rep 18, no. 10 (October 2016): 101. https://doi.org/10.1007/s11886-016-0779-9.

PMID
27568795
Full Text

Voora, Deepak, A Koneti Rao, Gauthami S. Jalagadugula, Rachel Myers, Emily Harris, Thomas L. Ortel, and Geoffrey S. Ginsburg. “Systems Pharmacogenomics Finds RUNX1 Is an Aspirin-Responsive Transcription Factor Linked to Cardiovascular Disease and Colon Cancer.” Ebiomedicine 11 (September 2016): 157–64. https://doi.org/10.1016/j.ebiom.2016.08.021.

PMID
27566955
Full Text

Cohen, Alexander T., Robert A. Harrington, Samuel Z. Goldhaber, Russell D. Hull, Brian L. Wiens, Alex Gold, Adrian F. Hernandez, C Michael Gibson, and C Michael APEX Investigators. “Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients.” N Engl J Med 375, no. 6 (August 11, 2016): 534–44. https://doi.org/10.1056/NEJMoa1601747.

PMID
27232649
Full Text

Gauthier, Karine, Grégoire Le Gal, Sudeep Shivakumar, David Anderson, Isabelle Chagnon, Susan Solymoss, Thomas Ortel, Erik Yeo, Clive Kearon, and Marc Rodger. “Inter-observer reliability of the HERDOO2 clinical decision rule.” Thromb Res 141 (May 2016): 136–38. https://doi.org/10.1016/j.thromres.2016.03.015.

PMID
27031923
Full Text

Pavon, Juliessa M., Soheir S. Adam, Zayd A. Razouki, Jennifer R. McDuffie, Paul F. Lachiewicz, Andrzej S. Kosinski, Christopher A. Beadles, Thomas L. Ortel, Avishek Nagi, and John W. Williams. “Effectiveness of Intermittent Pneumatic Compression Devices for Venous Thromboembolism Prophylaxis in High-Risk Surgical Patients: A Systematic Review.” J Arthroplasty 31, no. 2 (February 2016): 524–32. https://doi.org/10.1016/j.arth.2015.09.043.

PMID
26525487
Full Text

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