Thomas Lee Ortel

Thomas Lee Ortel

Chief, Division of Hematology in the Department of Medicine

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.

Appointments and Affiliations

  • Chief, Division of Hematology in the Department of Medicine
  • Professor of Medicine
  • Professor of Pathology
  • Member of the Duke Cancer Institute

Contact Information

Education

  • Duke University, 1991
  • Duke University, 1988
  • M.D. Indiana University at Indianapolis, 1985
  • Ph.D. Indiana University at Bloomington, 1983

Awards, Honors, and Distinctions

  • Pew Scholars in the Biomedical Sciences. Pew Charitable Trusts, The. 1995

Courses Taught

  • PATHOL 293: Research Independent Study
  • PATHOL 793: Research Independent Study

In the News

Representative Publications

  • Erkan, D; Ortel, TL; Lockshin, MD, Warfarin in antiphospholipid syndrome--time to explore new horizons., The Journal of Rheumatology, vol 32 no. 2 (2005), pp. 208-212 [abs].
  • Rand, JH; Wu, X-X; Lapinski, R; van Heerde, WL; Reutelingsperger, CP; Chen, PP; Ortel, TL, Detection of antibody-mediated reduction of annexin A5 anticoagulant activity in plasmas of patients with the antiphospholipid syndrome., Blood, vol 104 no. 9 (2004), pp. 2783-2790 [10.1182/blood-2004-01-0203] [abs].
  • Potti, A; Rusconi, CP; Sullenger, BA; Ortel, TL, Regulatable aptamers in medicine: focus on antithrombotic strategies., Expert Opin Biol Ther, vol 4 no. 10 (2004), pp. 1641-1647 [10.1517/14712598.4.10.1641] [abs].
  • James, AH; Lukes, AS; Brancazio, LR; Thames, E; Ortel, TL, Use of a new platelet function analyzer to detect von Willebrand disease in women with menorrhagia., American Journal of Obstetrics and Gynecology, vol 191 no. 2 (2004), pp. 449-455 [10.1016/j.ajog.2004.03.009] [abs].
  • Lundblad, RL; Bradshaw, RA; Gabriel, D; Ortel, TL; Lawson, J; Mann, KG, A review of the therapeutic uses of thrombin., Thrombosis and Haemostasis, vol 91 no. 5 (2004), pp. 851-860 [10.1160/TH03-12-0792] [abs].
  • O'shea, SI; Lawson, JH; Reddan, D; Murphy, M; Ortel, TL, Hypercoagulable states and antithrombotic strategies in recurrent vascular access site thrombosis., Journal of Vascular Surgery, vol 38 no. 3 (2003), pp. 541-548 [10.1016/s0741-5214(03)00321-5] [abs].
  • Lewis, DA; Pound, ML; Ortel, TL, 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, vol 89 no. 5 (2003), pp. 795-802 [abs].
  • Izumi, T; Pound, ML; Su, Z; Iverson, GM; Ortel, TL, Anti-beta(2)-glycoprotein I antibody-mediated inhibition of activated protein C requires binding of beta(2)-glycoprotein I to phospholipids., Thrombosis and Haemostasis, vol 88 no. 4 (2002), pp. 620-626 [abs].
  • Rusconi, CP; Scardino, E; Layzer, J; Pitoc, GA; Ortel, TL; Monroe, D; Sullenger, BA, RNA aptamers as reversible antagonists of coagulation factor IXa., Nature, vol 419 no. 6902 (2002), pp. 90-94 [10.1038/nature00963] [abs].
  • Su, Z; Izumi, T; Thames, EH; Lawson, JH; Ortel, TL, Antiphospholipid antibodies after surgical exposure to topical bovine thrombin., The Journal of Laboratory and Clinical Medicine, vol 139 no. 6 (2002), pp. 349-356 [10.1067/mlc.2002.123950] [abs].
  • 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; 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, vol 99 no. 8 (2002), pp. 2828-2834 [10.1182/blood.v99.8.2828] [abs].
  • Hansen, KE; Kong, DF; Moore, KD; Ortel, TL, Risk factors associated with thrombosis in patients with antiphospholipid antibodies., The Journal of Rheumatology, vol 28 no. 9 (2001), pp. 2018-2024 [abs].
  • Izumi, T; Kim, SW; Greist, A; Macedo-Ribeiro, S; Fuentes-Prior, P; Bode, W; Kane, WH; Ortel, TL, Fine mapping of inhibitory anti-factor V antibodies using factor V C2 domain mutants. Identification of two antigenic epitopes involved in phospholipid binding., Thrombosis and Haemostasis, vol 85 no. 6 (2001), pp. 1048-1054 [abs].
  • Lewis, DA; Moore, KD; Ortel, TL, Factor VIII Arg2304 --> His binds to phosphatidylserine and is a functional cofactor in the factor X-ase complex., Thrombosis and Haemostasis, vol 85 no. 2 (2001), pp. 260-264 [abs].
  • Ortel, TL; Mercer, MC; Thames, EH; Moore, KD; Lawson, JH, Immunologic impact and clinical outcomes after surgical exposure to bovine thrombin., Annals of Surgery, vol 233 no. 1 (2001), pp. 88-96 [10.1097/00000658-200101000-00014] [abs].
  • Goel, N; Ortel, TL; Bali, D; Anderson, JP; Gourley, IS; Smith, H; Morris, CA; DeSimone, M; Branch, DW; Ford, P; Berdeaux, D; Roubey, RA; Kostyu, DD; Kingsmore, SF; Thiel, T; Amos, C; Seldin, MF, Familial antiphospholipid antibody syndrome: criteria for disease and evidence for autosomal dominant inheritance., Arthritis and Rheumatism, vol 42 no. 2 (1999), pp. 318-327 [10.1002/1529-0131(199902)42:2<318::AID-ANR15>3.0.CO;2-5] [abs].