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

Clark, NP, Douketis, JD, Hasselblad, V, Schulman, S, Kindzelski, AL, and Ortel, TL. "Predictors of Perioperative Major Bleeding in Patients who interrupt Warfarin for an Elective Surgery or Procedure: Analysis of the BRIDGE Trial." American Heart Journal (September 2017).

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Kuter, DJ, Konkle, BA, Hamza, TH, Uhl, L, Assmann, SF, Kiss, JE, Kaufman, RM, Key, NS, Sachais, BS, Hess, JR, Ness, P, McCrae, KR, Leissinger, C, Strauss, RG, McFarland, JG, Neufeld, E, Bussel, JB, and Ortel, TL. "Clinical outcomes in a cohort of patients with heparin-induced thrombocytopenia." American journal of hematology 92, no. 8 (August 2017): 730-738.

PMID
28388835
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Gibson, CM, Korjian, S, Chi, G, Daaboul, Y, Jain, P, Arbetter, D, Goldhaber, SZ, Hull, R, Hernandez, AF, Lopes, RD, Gold, A, Cohen, AT, Harrington, RA, and APEX Investigators, . "Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely Ill Medical Patients: An APEX Trial Substudy." Journal of the American Heart Association 6, no. 7 (July 11, 2017).

PMID
28698258
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Arepally, GM. "Heparin-induced thrombocytopenia." Blood 129, no. 21 (May 2017): 2864-2872. (Review)

PMID
28416511
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Sun, JL, Boyle, SH, Samad, Z, Babyak, MA, Wilson, JL, Kuhn, C, Becker, RC, Ortel, TL, Williams, RB, Rogers, JG, O'Connor, CM, Velazquez, EJ, and Jiang, W. "Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients." European journal of preventive cardiology 24, no. 6 (April 2017): 591-599.

PMID
28067532
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Rodger, MA, Le Gal, G, Anderson, DR, Schmidt, J, Pernod, G, Kahn, SR, Righini, M, Mismetti, P, Kearon, C, Meyer, G, Elias, A, Ramsay, T, Ortel, TL, Huisman, MV, Kovacs, MJ, and REVERSE II Study Investigators, . "Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study." BMJ (Clinical research ed.) 356 (March 17, 2017): j1065-.

PMID
28314711
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Khorana, AA, Francis, CW, Kuderer, NM, Carrier, M, Ortel, TL, Wun, T, Rubens, D, Hobbs, S, Iyer, R, Peterson, D, Baran, A, Kaproth-Joslin, K, and Lyman, GH. "Dalteparin thromboprophylaxis in cancer patients at high risk for venous thromboembolism: A randomized trial." March 2017.

PMID
28139259
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Feigal, JP, Boyle, SH, Samad, Z, Velazquez, EJ, Wilson, JL, Becker, RC, Williams, RB, Kuhn, CM, Ortel, TL, Rogers, JG, O'Connor, CM, and Jiang, W. "Associations between positive emotional well-being and stress-induced myocardial ischemia: Well-being scores predict exercise-induced ischemia." Journal of psychosomatic research 93 (February 2017): 14-18.

PMID
28107887
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Doherty, JU, Gluckman, TJ, Hucker, WJ, Januzzi, JL, Ortel, TL, Saxonhouse, SJ, and Spinler, SA. "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." Journal of the American College of Cardiology 69, no. 7 (February 2017): 871-898.

PMID
28081965
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Welsby, IJ, Krakow, EF, Heit, JA, Williams, EC, Arepally, GM, Bar-Yosef, S, Kong, DF, Martinelli, S, Dhakal, I, Liu, WW, Krischer, J, and Ortel, TL. "The association of anti-platelet factor 4/heparin antibodies with early and delayed thromboembolism after cardiac surgery." Journal of thrombosis and haemostasis : JTH 15, no. 1 (January 2017): 57-65.

PMID
27714919
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