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

Haykal, Tarek, Yazan Zayed, Josiane Kerbage, Smit Deliwala, Chandler A. Long, and Thomas L. Ortel. “Meta-analysis and systematic review of randomized controlled trials assessing the role of thromboprophylaxis after vascular surgery.” J Vasc Surg Venous Lymphat Disord 10, no. 3 (May 2022): 767-777.e3. https://doi.org/10.1016/j.jvsv.2021.08.019.

PMID
34508872
Full Text

Myers, Rachel A., Thomas L. Ortel, Alexander Waldrop, Sandeep Dave, Geoffrey S. Ginsburg, and Deepak Voora. “Aspirin effects on platelet gene expression are associated with a paradoxical, increase in platelet function.” Br J Clin Pharmacol 88, no. 5 (May 2022): 2074–83. https://doi.org/10.1111/bcp.15127.

PMID
34705291
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See, Isaac, Allison Lale, Paige Marquez, Michael B. Streiff, Allison P. Wheeler, Naomi K. Tepper, Emily Jane Woo, et al. “Case Series of Thrombosis With Thrombocytopenia Syndrome After COVID-19 Vaccination-United States, December 2020 to August 2021.” Ann Intern Med 175, no. 4 (April 2022): 513–22. https://doi.org/10.7326/M21-4502.

PMID
35038274
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Wiercioch, Wojtek, Robby Nieuwlaat, Yuan Zhang, Pablo Alonso-Coello, Philipp Dahm, Alfonso Iorio, Veena Manja, et al. “New methods facilitated the process of prioritizing questions and health outcomes in guideline development.” J Clin Epidemiol 143 (March 2022): 91–104. https://doi.org/10.1016/j.jclinepi.2021.11.031.

PMID
34843861
Full Text

Vestal, Mark L., Kimberly Hodulik, Jennifer Mando-Vandrick, Michael L. James, Thomas L. Ortel, Matthew Fuller, Maria Notini, Mark Friedland, and Ian J. Welsby. “Andexanet alfa and four-factor prothrombin complex concentrate for reversal of apixaban and rivaroxaban in patients diagnosed with intracranial hemorrhage.” J Thromb Thrombolysis 53, no. 1 (January 2022): 167–75. https://doi.org/10.1007/s11239-021-02495-3.

PMID
34101050
Full Text

Nieuwlaat, Robby, Wojtek Wiercioch, Jan L. Brozek, Nancy Santesso, Robert Kunkle, Pablo Alonso-Coello, David R. Anderson, et al. “How to write a guideline: a proposal for a manuscript template that supports the creation of trustworthy guidelines.” Blood Adv 5, no. 22 (November 23, 2021): 4721–26. https://doi.org/10.1182/bloodadvances.2020003577.

PMID
34521104
Full Text

Jindal, Ankur K., Jasmina Ahluwalia, Rajiv Suku, Deepti Suri, Karen Nuytemans, Thomas L. Ortel, Margaret A. Pericak-Vance, Jeffery M. Vance, and Surjit Singh. “Successful Management of Catastrophic Thrombotic Storm in a Young Boy: A Case Report From Northern India.” J Pediatr Hematol Oncol 43, no. 8 (November 1, 2021): e1132–35. https://doi.org/10.1097/MPH.0000000000002069.

PMID
33560088
Full Text

Streiff, Michael B., Bjorn Holmstrom, Dana Angelini, Aneel Ashrani, Amro Elshoury, John Fanikos, Kleber Yotsumoto Fertrin, et al. “Cancer-Associated Venous Thromboembolic Disease, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.” J Natl Compr Canc Netw 19, no. 10 (October 15, 2021): 1181–1201. https://doi.org/10.6004/jnccn.2021.0047.

PMID
34666313
Full Text

Barbhaiya, Medha, Stephane Zuily, Yasaman Ahmadzadeh, Mary-Carmen Amigo, Tadej Avcin, Maria Laura Bertolaccini, D Ware Branch, et al. “Development of a New International Antiphospholipid Syndrome Classification Criteria Phase I/II Report: Generation and Reduction of Candidate Criteria.” Arthritis Care Res (Hoboken) 73, no. 10 (October 2021): 1490–1501. https://doi.org/10.1002/acr.24520.

PMID
33253499
Full Text

Pages