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

Potti, Anil, Veshana Ramiah, and Thomas L. Ortel. “Thrombophilia and thrombosis in thrombotic thrombocytopenic purpura..” Seminars in Thrombosis and Hemostasis 31, no. 6 (December 2005): 652–58. https://doi.org/10.1055/s-2005-925471.

PMID
16388416
Full Text

Haynes, Barton F., Judith Fleming, E William St Clair, Herman Katinger, Gabriela Stiegler, Renate Kunert, James Robinson, et al. “Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies..” Science 308, no. 5730 (June 24, 2005): 1906–8. https://doi.org/10.1126/science.1111781.

PMID
15860590
Full Text

Lewis, Deborah A., Niels Bovenschen, Koen Mertens, Jan Voorberg, and Thomas L. Ortel. “Phospholipid vesicles interfere with the binding of antibody fragments to the light chain of factor VIII..” Thrombosis and Haemostasis 93, no. 5 (May 2005): 833–41. https://doi.org/10.1160/th04-11-0729.

PMID
15886796
Full Text

Lukes, Andrea S., Stephanie Perry, and Thomas L. Ortel. “von Willebrand's disease diagnosed after menorrhagia worsened from levonorgestrel intrauterine system..” Obstetrics and Gynecology 105, no. 5 Pt 2 (May 2005): 1223–26. https://doi.org/10.1097/01.aog.0000157758.94890.59.

PMID
15863590
Full Text

Lawson, Jeffrey H., Kellie A. Lynn, Reed M. Vanmatre, Taymon Domzalski, Keith F. Klemp, Thomas L. Ortel, Laura E. Niklason, and William Parker. “Antihuman factor V antibodies after use of relatively pure bovine thrombin..” The Annals of Thoracic Surgery 79, no. 3 (March 2005): 1037–38. https://doi.org/10.1016/j.athoracsur.2003.09.110.

PMID
15734434
Full Text

James, Andra H., Leo R. Brancazio, and Thomas L. Ortel. “Thrombosis, thrombophilia, and thromboprophylaxis in pregnancy..” Clinical Advances in Hematology & Oncology : H&O 3, no. 3 (March 2005): 187–97.

PMID
16166990
Scholars@Duke

Erkan, Doruk, Thomas L. Ortel, and Michael D. Lockshin. “Warfarin in antiphospholipid syndrome--time to explore new horizons..” The Journal of Rheumatology 32, no. 2 (February 2005): 208–12.

PMID
15693072
Scholars@Duke

Fassas, Athanasios, Bart Barlogie, James Feusner, Neil E. Kay, and John R. Wingard. “Highlights from the 46 th annual meeting of the American Society of Hematology..” Clinical Advances in Hematology & Oncology : H&O 3, no. 2 (February 2005): 111–16.

PMID
16166978
Scholars@Duke

Costello, Rebecca, Joan Young, Rebecca Burkholder, Joseph Cranston, Thomas L. Ortel, Steven Dentali, Richard Cotter, Julie O’sullivan Maillet, Bruce Hawkins, and W. Craig Hooper. “Dialogue with patient care organizations..” Thrombosis Research 117, no. 1–2 (January 2005): 211–22. https://doi.org/10.1016/j.thromres.2005.07.004.

PMID
16125754
Full Text

Pages