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

Welty-Wolf, K. E., M. S. Carraway, D. L. Miller, T. L. Ortel, M. Ezban, A. J. Ghio, S. Idell, and C. A. Piantadosi. “Coagulation blockade prevents sepsis-induced respiratory and renal failure in baboons.” American Journal of Respiratory and Critical Care Medicine 164, no. 10 I (November 15, 2001): 1988–96. https://doi.org/10.1164/ajrccm.164.10.2105027.

Full Text

Schoenecker, J. G., R. K. Johnson, A. P. Lesher, J. D. Day, S. D. Love, M. R. Hoffman, T. L. Ortel, W. Parker, and J. H. Lawson. “Exposure of mice to topical bovine thrombin induces systemic autoimmunity..” Am J Pathol 159, no. 5 (November 2001): 1957–69. https://doi.org/10.1016/S0002-9440(10)63043-X.

PMID
11696457
Full Text

Welty-Wolf, K. E., M. S. Carraway, S. Idell, T. L. Ortel, M. Ezban, and C. A. Piantadosi. “Tissue factor in experimental acute lung injury..” Semin Hematol 38, no. 4 Suppl 12 (October 2001): 35–38.

PMID
11735108
Scholars@Duke

Hansen, K. E., D. F. Kong, K. D. Moore, and T. L. Ortel. “Risk factors associated with thrombosis in patients with antiphospholipid antibodies..” J Rheumatol 28, no. 9 (September 2001): 2018–24.

PMID
11550969
Scholars@Duke

Sands, J. J., S. A. Nudo, K. D. Moore, and T. L. Ortel. “Antibodies to prothrombin, factor V, and beta2-glycoprotein I and vascular access thrombosis..” Asaio J 47, no. 5 (September 2001): 507–10.

PMID
11575827
Scholars@Duke

McNeeley, P. A., J. S. Dlott, R. A. Furie, R. M. Jack, T. L. Ortel, D. A. Triplett, E. J. Victoria, and M. D. Linnik. “Beta2-glycoprotein I-dependent anticardiolipin antibodies preferentially bind the amino terminal domain of beta2-glycoprotein I..” Thromb Haemost 86, no. 2 (August 2001): 590–95.

PMID
11522008
Scholars@Duke

Izumi, T., S. W. Kim, A. Greist, S. Macedo-Ribeiro, P. Fuentes-Prior, W. Bode, W. H. Kane, and T. L. Ortel. “Fine mapping of inhibitory anti-factor V antibodies using factor V C2 domain mutants. Identification of two antigenic epitopes involved in phospholipid binding..” Thromb Haemost 85, no. 6 (June 2001): 1048–54.

PMID
11434683
Scholars@Duke

Lewis, D. A., K. D. Moore, and T. L. Ortel. “ His binds to phosphatidylserine and is a functional cofactor in the factor X-ase complex..” Thromb Haemost 85, no. 2 (February 2001): 260–64.

PMID
11246544
Scholars@Duke

McNeeley, P. A., J. S. Dlott, R. A. Furie, R. M. Jack, T. L. Ortel, D. A. Triplett, E. J. Victoria, and M. D. Linnik. “β2-Glycoprotein I-dependent anticardiolipin antibodies preferentially bind the amino terminal domain of β2-glycoprotein I.” Thrombosis and Haemostasis 86, no. 2 (January 1, 2001): 590–95.

Scholars@Duke

Welty-Wolf, K. E., M. S. Carraway, S. Idell, T. L. Ortel, M. Ezban, and C. A. Piantadosi. “Tissue factor in experimental acute lung injury.” Seminars in Hematology 38, no. 4 SUPPL. 12 (January 1, 2001): 35–38.

Scholars@Duke

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