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

Grants

Publications

Cohen, Hannah, Maria J. Cuadrado, Doruk Erkan, Ali Duarte-Garcia, David A. Isenberg, Jason S. Knight, Thomas L. Ortel, et al. “16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends.” Lupus 29, no. 12 (October 2020): 1571–93. https://doi.org/10.1177/0961203320950461.

PMID
33100166
Full Text

Ortel, Thomas L., Sreelatha Meleth, Diane Catellier, Mark Crowther, Doruk Erkan, Paul R. Fortin, David Garcia, et al. “Recurrent thrombosis in patients with antiphospholipid antibodies and an initial venous or arterial thromboembolic event: A systematic review and meta-analysis.” J Thromb Haemost 18, no. 9 (September 2020): 2274–86. https://doi.org/10.1111/jth.14936.

PMID
32484606
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Thachil, Jecko, Nicole P. Juffermans, Marco Ranucci, Jean M. Connors, Theodore E. Warkentin, Thomas L. Ortel, Marcel Levi, Toshiaki Iba, and Jerrold H. Levy. “ISTH DIC subcommittee communication on anticoagulation in COVID-19.” J Thromb Haemost 18, no. 9 (September 2020): 2138–44. https://doi.org/10.1111/jth.15004.

PMID
32881336
Full Text

Sung, Anthony D., Richard C. Yen, Yiqun Jiao, Alyssa Bernanke, Deborah A. Lewis, Sara E. Miller, Zhiguo Li, et al. “Fibrinogen-Coated Albumin Nanospheres Prevent Thrombocytopenia-Related Bleeding.” Radiat Res 194, no. 2 (August 1, 2020): 162–72. https://doi.org/10.1667/RADE-20-00016.

PMID
32845987
Full Text

Friede, Kevin A., Margaret M. Infeld, Ru San Tan, Holly J. Knickerbocker, Rachel A. Myers, Laura G. Dubois, J Will Thompson, et al. “Influence of Sex on Platelet Reactivity in Response to Aspirin.” J Am Heart Assoc 9, no. 14 (July 21, 2020): e014726. https://doi.org/10.1161/JAHA.119.014726.

PMID
32654613
Full Text

Root, A. G., R. D. Raiff, T. L. Ortel, and K. L. Hodulik. “Initiation of Emicizumab Therapy in an Adult Patient With Hemophilia A With Inhibitors and Associated Drug Cost Savings.” Journal of Pharmacy Technology 36, no. 3 (June 1, 2020): 110–13. https://doi.org/10.1177/8755122520906291.

Full Text

Wiercioch, Wojtek, Robby Nieuwlaat, Elie A. Akl, Robert Kunkle, Kendall E. Alexander, Adam Cuker, Anita Rajasekhar, et al. “Methodology for the American Society of Hematology VTE guidelines: current best practice, innovations, and experiences.” Blood Adv 4, no. 10 (May 26, 2020): 2351–65. https://doi.org/10.1182/bloodadvances.2020001768.

PMID
32453843
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Khatib, Rasha, Stephanie Ross, Sean Alexander Kennedy, Ivan D. Florez, Thomas L. Ortel, Robby Nieuwlaat, Ignacio Neumann, et al. “Home vs hospital treatment of low-risk venous thromboembolism: a systematic review and meta-analysis.” Blood Adv 4, no. 3 (February 11, 2020): 500–513. https://doi.org/10.1182/bloodadvances.2019001223.

PMID
32040553
Full Text

Refaai, Majed A., Grace Conley, Thomas L. Ortel, and John L. Francis. “Evaluation of a rapid and automated heparin-induced thrombocytopenia immunoassay.” In Int J Lab Hematol, 41:478–84, 2019. https://doi.org/10.1111/ijlh.13029.

PMID
30986338
Full Text

Hashmi, Nazish K., Kamrouz Ghadimi, Amudan J. Srinivasan, Yi-Ju Li, Robert D. Raiff, Jeffrey G. Gaca, Adam G. Root, et al. “Three-factor prothrombin complex concentrates for refractory bleeding after cardiovascular surgery within an algorithmic approach to haemostasis.” Vox Sang 114, no. 4 (May 2019): 374–85. https://doi.org/10.1111/vox.12774.

PMID
30937927
Full Text

Pages