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

Welty-Wolf, KE, Carraway, MS, Ortel, TL, and Piantadosi, CA. "Coagulation and inflammation in acute lung injury." Thromb Haemost 88, no. 1 (July 2002): 17-25. (Review)

PMID
12152667
Scholars@Duke

Su, Z, Izumi, T, Thames, EH, Lawson, JH, and Ortel, TL. "Antiphospholipid antibodies after surgical exposure to topical bovine thrombin." The Journal of Laboratory and Clinical Medicine 139, no. 6 (June 2002): 349-356.

PMID
12066133
Full Text

van den Brink, EN, Bril, WS, Turenhout, EAM, Zuurveld, M, Bovenschen, N, Peters, M, Yee, TT, Mertens, K, Lewis, DA, Ortel, TL, Lollar, P, Scandella, D, and Voorberg, J. "Two classes of germline genes both derived from the V(H)1 family direct the formation of human antibodies that recognize distinct antigenic sites in the C2 domain of factor VIII." Blood 99, no. 8 (April 15, 2002): 2828-2834.

PMID
11929772
Scholars@Duke

Su, Z, Braun, PJ, Klemp, KF, Baker, KR, Thames, EH, and Ortel, TL. "Abnormal optical waveform profiles in coagulation assays from patients with antiphospholipid antibodies." Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis 13, no. 1 (January 2002): 7-17.

PMID
11994562
Full Text

O'Shea, SI, Sands, JJ, Nudo, SA, and Ortel, TL. "Frequency of anti-heparin-platelet factor 4 antibodies in hemodialysis patients and correlation with recurrent vascular access thrombosis." Am J Hematol 69, no. 1 (January 2002): 72-73.

PMID
11835336
Scholars@Duke

Izumi, T, Pound, ML, Su, Z, Iverson, GM, and Ortel, TL. "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 (2002): 620-626.

Scholars@Duke

O'Shea, SI, Sands, JJ, Nudo, SA, and Ortel, TL. "Mutation of bcl-x gene in non-Hodgkin's lymphoma." American Journal of Hematology 69, no. 1 (2002): 74-76.

PMID
11835337
Full Text

Welty-Wolf, KE, Carraway, MS, Miller, DL, Ortel, TL, Ezban, M, Ghio, AJ, Idell, S, and Piantadosi, CA. "Coagulation blockade prevents sepsis-induced respiratory and renal failure in baboons." American Journal of Respiratory and Critical Care Medicine 164, no. 10 I (November 15, 2001): 1988-1996.

Full Text

Welty-Wolf, KE, Carraway, MS, Miller, DL, Ortel, TL, Ezban, M, Ghio, AJ, Idell, S, and Piantadosi, CA. "Coagulation blockade prevents sepsis-induced respiratory and renal failure in baboons." American Journal of Respiratory and Critical Care Medicine 164, no. 10 Pt 1 (November 2001): 1988-1996.

PMID
11734456
Full Text

Schoenecker, JG, Johnson, RK, Lesher, AP, Day, JD, Love, SD, Hoffman, MR, Ortel, TL, Parker, W, and Lawson, JH. "Exposure of mice to topical bovine thrombin induces systemic autoimmunity." Am J Pathol 159, no. 5 (November 2001): 1957-1969.

PMID
11696457
Full Text

Pages