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

Provenzale, JM, Barboriak, DP, Davey, IC, and Ortel, TL. "Cerebrovascular disease risk factors: neuroradiologic findings in patients with activated protein C resistance." Radiology 207, no. 1 (April 1998): 85-89.

PMID
9530303
Full Text

Provenzale, JM, Barboriak, DP, Allen, NB, and Ortel, TL. "Antiphospholipid antibodies: findings at arteriography." Ajnr. American Journal of Neuroradiology 19, no. 4 (April 1998): 611-616.

PMID
9576644
Scholars@Duke

Provenzale, JM, Barboriak, DP, and Ortel, TL. "Dural sinus thrombosis associated with activated protein C resistance: MR imaging findings and proband identification." AJR Am J Roentgenol 170, no. 2 (February 1998): 499-502.

PMID
9456973
Full Text

Provenzale, JM, Spritzer, CE, Nelson, RC, and Ortel, TL. "Disseminated thrombosis in primary antiphospholipid syndrome: MR findings." Eur J Radiol 26, no. 3 (February 1998): 244-247.

PMID
9587749
Scholars@Duke

Provenzale, JM, Ortel, TL, and Allen, NB. "Systemic thrombosis in patients with antiphospholipid antibodies: lesion distribution and imaging findings." AJR Am J Roentgenol 170, no. 2 (February 1998): 285-290.

PMID
9456930
Full Text

Schwartz, MA, Zimhony, O, Moll, S, Ortel, TL, Pechlaner, C, Gritsch, W, Wiedermann, C, Yu, DR, Miller, R, and Bray, PF. "Diagnosis of pulmonary embolism [5] (multiple letters)." New England Journal of Medicine 339, no. 15 (1998): 1084-1085.

PMID
9767005
Full Text

Manoharan, A, D'Angelo, A, Valle, PD, Crippa, L, Moll, S, and Ortel, TL. "Monitoring warfarin therapy in patients with lupus anticoagulants [1] (multiple letters)." Annals of Internal Medicine 128, no. 6 (1998): 504-505.

PMID
9499338
Scholars@Duke

Korompilias, AV, Gilkeson, GS, Ortel, TL, Seaber, AV, and Urbaniak, JR. "Anticardiolipin antibodies and osteonecrosis of the femoral head." Clin Orthop Relat Res, no. 345 (December 1997): 174-180.

PMID
9418637
Scholars@Duke

Moll, S, and Ortel, TL. "Monitoring warfarin therapy in patients with lupus anticoagulants." Ann Intern Med 127, no. 3 (August 1, 1997): 177-185.

PMID
9245222
Scholars@Duke

Moll, S, and Ortel, TL. "Annals of Internal Medicine: Monitoring warfarin therapy in patients with lupus anticoagulants." Annals of Internal Medicine 127, no. 3 (August 1, 1997): 177-185.

Scholars@Duke

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