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

Doherty, DC, Ortel, TL, de Bruijn, N, Greenberg, CS, and Van Trigt, P. ""Heparin-free" cardiopulmonary bypass: first reported use of heparinoid (Org 10172) to provide anticoagulation for cardiopulmonary bypass." Anesthesiology 73, no. 3 (September 1990): 562-565.

PMID
1697448
Scholars@Duke

Ortel, TL, Kallianos, J, and Gallis, HA. "Group C streptococcal arthritis: case report and review." Rev Infect Dis 12, no. 5 (September 1990): 829-837. (Review)

PMID
2237126
Scholars@Duke

Kane, WH, Devore-Carter, D, and Ortel, TL. "Expression and characterization of recombinant human factor V and a mutant lacking a major portion of the connecting region." Biochemistry 29, no. 29 (July 24, 1990): 6762-6768.

PMID
2397212
Scholars@Duke

Ortel, TL. "Author's reply." American Journal of Hematology 31, no. 3 (July 1989): 220-220.

Full Text

Ozsoylu, S, and Ortel, TL. "High-dose intravenous methylprednisolone for Kasabach-Merritt syndrome." American Journal of Hematology 31, no. 3 (1989): 219-220.

PMID
2741917
Scholars@Duke

Ortel, TL, Onorato, JJ, Bedrosian, CL, and Kaufman, RE. "Antifibrinolytic therapy in the management of the Kasabach Merritt syndrome." Am J Hematol 29, no. 1 (September 1988): 44-48.

PMID
3177369
Scholars@Duke

Ortel, TL, Bedrosian, CL, and Simel, DL. "Arsenic poisoning and seizures." N C Med J 48, no. 12 (December 1987): 627-630.

PMID
3480434
Scholars@Duke

Takahashi, N, Takahashi, Y, Ortel, TL, Lozier, JN, Ishioka, N, and Putnam, FW. "Purification of glycopeptides of human plasma proteins by high-performance liquid chromatography." J Chromatogr 317 (December 28, 1984): 11-26.

PMID
6530429
Scholars@Duke

Ortel, TL, Takahashi, N, and Putnam, FW. "Structural model of human ceruloplasmin based on internal triplication, hydrophilic/hydrophobic character, and secondary structure of domains." Proceedings of the National Academy of Sciences of the United States of America 81, no. 15 (August 1984): 4761-4765.

PMID
6589622
Full Text

Takahashi, N, Ortel, TL, and Putnam, FW. "Single-chain structure of human ceruloplasmin: the complete amino acid sequence of the whole molecule." Proceedings of the National Academy of Sciences of the United States of America 81, no. 2 (January 1984): 390-394.

PMID
6582496
Full Text

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