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

O’shea, Susan I., Jeffrey H. Lawson, Donal Reddan, Michael Murphy, and Thomas L. Ortel. “Hypercoagulable states and antithrombotic strategies in recurrent vascular access site thrombosis..” Journal of Vascular Surgery 38, no. 3 (September 2003): 541–48. https://doi.org/10.1016/s0741-5214(03)00321-5.

PMID
12947274
Full Text

Su, Zuowei, Tomonori Izumi, and Thomas L. Ortel. “Prothrombin and beta 2-glycoprotein I frequently contribute to antiphospholipid antibody interactions with phospholipids and the generation of abnormal waveform profiles in coagulation assays..” Thrombosis and Haemostasis 90, no. 2 (August 2003): 218–26. https://doi.org/10.1160/th02-09-0052.

PMID
12888868
Full Text

Lewis, Deborah A., Karen D. Moore, and Thomas L. Ortel. “Binding of factor VIII inhibitors to discrete regions of the factor VIII C2 domain disrupt phospholipid binding..” Blood Coagulation & Fibrinolysis : An International Journal in Haemostasis and Thrombosis 14, no. 4 (June 2003): 361–68. https://doi.org/10.1097/00001721-200306000-00007.

PMID
12945878
Full Text

Larned, Zoë L., Susan I. O’Shea, and Thomas L. Ortel. “Heparin-induced thrombocytopenia: clinical presentations and therapeutic management..” Clinical Advances in Hematology & Oncology : H&O 1, no. 6 (June 2003): 356–64.

PMID
16224435
Scholars@Duke

Lewis, Deborah A., Mary L. Pound, and Thomas L. Ortel. “Contributions of Asn2198, Met2199, and Phe2200 in the factor VIII C2 domain to cofactor activity, phospholipid-binding, and von Willebrand factor-binding..” Thrombosis and Haemostasis 89, no. 5 (May 2003): 795–802.

PMID
12719775
Scholars@Duke

Carraway, Martha Sue, Karen E. Welty-Wolf, Debra L. Miller, Thomas L. Ortel, Steven Idell, Andrew J. Ghio, Lars C. Petersen, and Claude A. Piantadosi. “Blockade of tissue factor: treatment for organ injury in established sepsis..” American Journal of Respiratory and Critical Care Medicine 167, no. 9 (May 2003): 1200–1209. https://doi.org/10.1164/rccm.200204-287oc.

PMID
12714343
Full Text

Perry, Stephanie L., and Thomas L. Ortel. “Clinical and laboratory evaluation of thrombophilia..” Clinics in Chest Medicine 24, no. 1 (March 2003): 153–70. https://doi.org/10.1016/s0272-5231(02)00054-0.

PMID
12685062
Full Text

O’Shea, Susan I., Thomas L. Ortel, and Eugene C. Kovalik. “Alternative methods of anticoagulation for dialysis-dependent patients with heparin-induced thrombocytopenia..” Seminars in Dialysis 16, no. 1 (January 2003): 61–67. https://doi.org/10.1046/j.1525-139x.2003.03014.x.

PMID
12535303
Full Text

Izumi, Tomonori, Mary L. Pound, Zuowei Su, G Michael Iverson, and Thomas L. Ortel. “Anti-beta(2)-glycoprotein I antibody-mediated inhibition of activated protein C requires binding of beta(2)-glycoprotein I to phospholipids..” Thrombosis and Haemostasis 88, no. 4 (October 2002): 620–26.

PMID
12362233
Scholars@Duke

Izumi, T., M. L. Pound, Z. Su, G. M. Iverson, and T. L. Ortel. “Anti-β2-glycoprotein I antibody-mediated inhibition of activated protein C requires binding of β2-glycoprotein I to phospholipids.” Thrombosis and Haemostasis 88, no. 4 (October 1, 2002): 620–26.

Scholars@Duke

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