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

Yusuf, HR, Hooper, WC, Grosse, SD, Parker, CS, Boulet, SL, and Ortel, TL. "Risk of venous thromboembolism occurrence among adults with selected autoimmune diseases: a study among a U.S. cohort of commercial insurance enrollees." Thrombosis research 135, no. 1 (January 2015): 50-57.

PMID
25456001
Full Text

Arepally, GM, and Ortel, TL. "Changing practice of anticoagulation: will target-specific anticoagulants replace warfarin?." Annual review of medicine 66 (January 2015): 241-253. (Review)

PMID
25587651
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Ortel, TL, Beckman, M, Muhlbaier, L, Reyes, N, Grant, A, Tcheng, J, Saber, I, and Thames, E. "Venous Thromboembolism (VTE) Surveillance: Incidence, Characteristics, and Initial Treatment of VTE Patients." BLOOD 124, no. 21 (December 6, 2014).

Scholars@Duke

Kahn, SR, Shapiro, S, Ducruet, T, Wells, PS, Rodger, MA, Kovacs, MJ, Anderson, D, Tagalakis, V, Morrison, DR, Solymoss, S, Miron, M-J, 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, J-P, 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 (December 2014): 1137-1141.

PMID
25183442
Full Text

Samad, Z, Boyle, S, Ersboll, M, Vora, AN, Zhang, Y, Becker, RC, Williams, R, Kuhn, C, Ortel, TL, Rogers, JG, O'Connor, CM, Velazquez, EJ, Jiang, W, and REMIT Investigators, . "Sex differences in platelet reactivity and cardiovascular and psychological response to mental stress in patients with stable ischemic heart disease: insights from the REMIT study." Journal of the American College of Cardiology 64, no. 16 (October 2014): 1669-1678.

PMID
25323254
Full Text

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 (October 2014): 306-313.

PMID
24464552
Full Text

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 (October 2014): 275-284.

PMID
24880800
Full Text

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
Full Text

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.

Full Text

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
Full Text

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