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

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, June 8, 2021. https://doi.org/10.1007/s11239-021-02495-3.

PMID
34101050
Full Text

Wiercioch, Wojtek, Robby Nieuwlaat, Philipp Dahm, Alfonso Iorio, Reem A. Mustafa, Ignacio Neumann, Bram Rochwerg, et al. “Development and application of health outcome descriptors facilitated decision-making in the production of practice guidelines.” J Clin Epidemiol 138 (May 13, 2021): 115–27. https://doi.org/10.1016/j.jclinepi.2021.04.016.

PMID
33992716
Full Text

Haykal, Tarek, Soheir Adam, Areeg Bala, Yazan Zayed, Smit Deliwala, Josiane Kerbage, Anoosha Ponnapalli, Srikanth Malladi, Varun Samji, and Thomas L. Ortel. “Thromboprophylaxis for orthopedic surgery; An updated meta-analysis.” Thromb Res 199 (March 2021): 43–53. https://doi.org/10.1016/j.thromres.2020.12.007.

PMID
33422802
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Infeld, Margaret, Kevin A. Friede, Tan Ru San, Holly J. Knickerbocker, Geoffrey S. Ginsburg, Thomas L. Ortel, and Deepak Voora. “Platelet reactivity in response to aspirin and ticagrelor in African-Americans and European-Americans.” J Thromb Thrombolysis 51, no. 2 (February 2021): 249–59. https://doi.org/10.1007/s11239-020-02327-w.

PMID
33159252
Full Text

Ridker, Paul M., Thomas L. Ortel, and Judith S. Hochman. “Equipoise, Trust, and the Need for Cardiologists to Randomly Assign Patients Into Anticoagulation Trials in the Time of COVID.” Circulation 142, no. 24 (December 15, 2020): 2296–98. https://doi.org/10.1161/CIRCULATIONAHA.120.052069.

PMID
33054374
Full Text

Daughety, Molly M., Andrew Morgan, Erin Frost, Chester Kao, Joyce Hwang, Rachel Tobin, Bhavik Patel, Matthew Fuller, Ian Welsby, and Thomas L. Ortel. “COVID-19 associated coagulopathy: Thrombosis, hemorrhage and mortality rates with an escalated-dose thromboprophylaxis strategy.” Thromb Res 196 (December 2020): 483–85. https://doi.org/10.1016/j.thromres.2020.10.004.

PMID
33091700
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), November 30, 2020. https://doi.org/10.1002/acr.24520.

PMID
33253499
Full Text

Devreese, Katrien M. J., Philip G. de Groot, Bas de Laat, Doruk Erkan, Emmanuel J. Favaloro, Ian Mackie, Marta Martinuzzo, et al. “Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis: Update of the guidelines for lupus anticoagulant detection and interpretation.” J Thromb Haemost 18, no. 11 (November 2020): 2828–39. https://doi.org/10.1111/jth.15047.

PMID
33462974
Full Text

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