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

Hunt, CM, Carson, KL, and Ortel, TL. "Combined factor IX and XI deficiency discovered at liver biopsy." Dig Dis Sci 42, no. 8 (August 1997): 1731-1733.

PMID
9286241
Scholars@Duke

Moll, S, McCloud, M, and Ortel, TL. "Subdural hematoma and lupus anticoagulants." Stroke 28, no. 3 (March 1997): 646-648.

PMID
9056625
Scholars@Duke

Layish, DT, Spritzer, CE, Ortel, TL, and Tapson, VF. "Helical computed tomography and magnetic resonance imaging in the diagnosis of venous thromboembolic disease: Case report and review of the literature." Clinical Pulmonary Medicine 4, no. 3 (January 1, 1997): 170-173. (Review)

Full Text

Lind, SE, Callas, PW, Golden, EA, Joyner, KA, and Ortel, TL. "Plasma levels of factors II, VII and X and their relationship to the international normalized ratio during chronic warfarin therapy." Blood Coagul Fibrinolysis 8, no. 1 (January 1997): 48-53.

PMID
9105637
Scholars@Duke

Moll, S, Igelhart, JD, and Ortel, TL. "Thrombocytopenia in association with a wandering spleen." American Journal of Hematology 53, no. 4 (December 1996): 259-263. (Review)

PMID
8948667
Full Text

Provenzale, JM, Barboriak, DP, Allen, NB, and Ortel, TL. "Patients with antiphospholipid antibodies: CT and MR findings of the brain." AJR Am J Roentgenol 167, no. 6 (December 1996): 1573-1578.

PMID
8956600
Full Text

Ortel, TL, Moore, KD, Quinn-Allen, M, and Kane, WH. "Factor v inhibitors associated with hemorrhagic symptoms bind to a limited region of the factor va light chain." Journal of Investigative Medicine 44, no. 3 (January 1, 1996).

Scholars@Duke

Ortel, TL, Moore, KD, Ezban, M, and Kane, WH. "Effect of heterologous factor V heavy chain sequences on the secretion of recombinant human factor VIII." Thromb Haemost 75, no. 1 (January 1996): 36-44.

PMID
8713777
Scholars@Duke

Provenzale, JM, Ortel, TL, and Nelson, RC. "Adrenal hemorrhage in patients with primary antiphospholipid syndrome: imaging findings." AJR Am J Roentgenol 165, no. 2 (August 1995): 361-364.

PMID
7618557
Full Text

Provenzale, JM, and Ortel, TL. "Anatomic distribution of venous thrombosis in patients with antiphospholipid antibody: imaging findings." AJR Am J Roentgenol 165, no. 2 (August 1995): 365-368.

PMID
7618558
Full Text

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