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, Andrea Bild, Holly K. Dressman, Deborah A. Lewis, Joseph R. Nevins, and Thomas L. Ortel. “Gene-expression patterns predict phenotypes of immune-mediated thrombosis..” Blood 107, no. 4 (February 15, 2006): 1391–96. https://doi.org/10.1182/blood-2005-07-2669.

PMID
16263789
Full Text

Hayward, C. P. M., P. Harrison, M. Cattaneo, T. L. Ortel, A. K. Rao, and A. K. Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. “Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function..” J Thromb Haemost 4, no. 2 (February 2006): 312–19. https://doi.org/10.1111/j.1538-7836.2006.01771.x.

PMID
16420557
Full Text

Ortel, Thomas L. “The antiphospholipid syndrome: what are we really measuring? How do we measure it? And how do we treat it?.” J Thromb Thrombolysis 21, no. 1 (February 2006): 79–83. https://doi.org/10.1007/s11239-006-5581-x.

PMID
16475047
Full Text

Welty-Wolf, Karen E., Martha S. Carraway, Thomas L. Ortel, Andrew J. Ghio, Steven Idell, Jack Egan, Xiaoyun Zhu, Jin-an Jiao, Hing C. Wong, and Claude A. Piantadosi. “Blockade of tissue factor-factor X binding attenuates sepsis-induced respiratory and renal failure..” Am J Physiol Lung Cell Mol Physiol 290, no. 1 (January 2006): L21–31. https://doi.org/10.1152/ajplung.00155.2005.

PMID
16100288
Full Text

Lewis, D. A., M. L. Pound, and T. L. Ortel. “The reactivity of paired plasma and serum samples are comparable in the anticardiolipin and anti-beta2-glycoprotein-1 ELISAs..” J Thromb Haemost 4, no. 1 (January 2006): 265–67. https://doi.org/10.1111/j.1538-7836.2005.01721.x.

PMID
16409482
Full Text

Lewis, Deborah A., Abraham Nyska, Anil Potti, Heather A. Hoke, Keith F. Klemp, Sandra M. Ward, Shyamal D. Peddada, Jogin Wu, and Thomas L. Ortel. “Hemostatic activation in a chemically induced rat model of severe hemolysis and thrombosis..” Thromb Res 118, no. 6 (2006): 747–53. https://doi.org/10.1016/j.thromres.2005.11.010.

PMID
16405975
Full Text

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

PMID
16388416
Full Text

Bennett-Guerrero, Elliott, Thomas F. Slaughter, William D. White, Ian J. Welsby, Charles S. Greenberg, Habib El-Moalem, and Thomas L. Ortel. “Preoperative anti-PF4/heparin antibody level predicts adverse outcome after cardiac surgery..” J Thorac Cardiovasc Surg 130, no. 6 (December 2005): 1567–72. https://doi.org/10.1016/j.jtcvs.2005.07.052.

PMID
16308000
Full Text

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