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

Devreese, KMJ, Ortel, TL, Pengo, V, de Laat, B, and Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies, . "Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH." Journal of Thrombosis and Haemostasis : Jth 16, no. 4 (April 2018): 809-813.

PMID
29532986
Full Text

Onwuemene, OA, Grambow, SC, Patel, CB, Mentz, RJ, Milano, CA, Rogers, JG, Metjian, AD, Arepally, GM, and Ortel, TL. "Indications for and outcomes of therapeutic plasma exchange after cardiac transplantation: A single center retrospective study." Journal of Clinical Apheresis (March 10, 2018).

PMID
29524240
Full Text

Rabinovich, A, Ducruet, T, and Kahn, SR. "Development of a clinical prediction model for the postthrombotic syndrome in a prospective cohort of patients with proximal deep vein thrombosis." Journal of Thrombosis and Haemostasis 16, no. 2 (February 2018): 262-270.

Full Text

Borst, AJ, Sudan, DL, Wang, LA, Neuss, MJ, Rothman, JA, and Ortel, TL. "Bleeding and thrombotic complications of pediatric liver transplant." January 19, 2018.

PMID
29350493
Full Text

Clark, NP, Douketis, JD, Hasselblad, V, Schulman, S, Kindzelski, AL, Ortel, TL, and BRIDGE Investigators, . "Predictors of perioperative major bleeding in patients who interrupt warfarin for an elective surgery or procedure: Analysis of the BRIDGE trial." American heart journal 195 (January 2018): 108-114.

PMID
29224638
Full Text

Nuytemans, K, Ortel, TL, Gomez, L, Hofmann, N, Alves, N, Dueker, N, Beecham, A, Whitehead, P, Hahn Estabrooks, S, Kitchens, CS, Erkan, D, Brandão, LR, James, AH, Kulkarni, R, Manco-Johnson, MJ, Pericak-Vance, MA, and Vance, JM. "Variants in chondroitin sulfate metabolism genes in thrombotic storm." Thrombosis research 161 (January 2018): 43-51.

PMID
29178990
Full Text

Kuter, DJ, Konkle, BA, Hamza, TH, Uhl, L, Assmann, SF, Kiss, JE, Kaufman, RM, Key, NS, Sachais, BS, Hess, JR, Ness, P, McCrae, KR, Leissinger, C, Strauss, RG, McFarland, JG, Neufeld, E, Bussel, JB, and Ortel, TL. "Clinical outcomes in a cohort of patients with heparin-induced thrombocytopenia." American journal of hematology 92, no. 8 (August 2017): 730-738.

PMID
28388835
Full Text

Gibson, CM, Korjian, S, Chi, G, Daaboul, Y, Jain, P, Arbetter, D, Goldhaber, SZ, Hull, R, Hernandez, AF, Lopes, RD, Gold, A, Cohen, AT, Harrington, RA, and APEX Investigators, . "Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely Ill Medical Patients: An APEX Trial Substudy." Journal of the American Heart Association 6, no. 7 (July 11, 2017).

PMID
28698258
Full Text

Arepally, GM. "Heparin-induced thrombocytopenia." Blood 129, no. 21 (May 2017): 2864-2872. (Review)

PMID
28416511
Full Text

Sun, JL, Boyle, SH, Samad, Z, Babyak, MA, Wilson, JL, Kuhn, C, Becker, RC, Ortel, TL, Williams, RB, Rogers, JG, O'Connor, CM, Velazquez, EJ, and Jiang, W. "Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients." European Journal of Preventive Cardiology 24, no. 6 (April 2017): 591-599.

PMID
28067532
Full Text

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