Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC

Investigator, Center for Heart and Lung Research,
The Feinstein Institute for Medical Research

Director, Anticoagulation and Clinical Thrombosis Services, Northwell Health

Professor of Medicine, Hofstra Northwell School of Medicine

Phone: (212) 434-6779

About the Investigator

Dr Spyropoulos received his medical degree from the University of Pennsylvania School of Medicine in Philadelphia in 1992. He completed his internship and residency in internal medicine at the University of New Mexico Health Sciences Center in Albuquerque, NM. He is board certified in Internal Medicine.

Dr. Spyropoulos was Founder and former Medical Director of the Clinical Thrombosis Center in Albuquerque, New Mexico. He is co-chair of the Council on Leadership of Thrombosis at Northwell Health System. He is also a Feinstein Investigator for the Center for Heart and Lung Research as part of the Feinstein Institute of Medical Research. He is a Fellow of the American College of Physicians, American College of Chest Physicians, International Academy of Clinical and Applied Thrombosis/Haemostasis, and the Royal College of Physicians, Canada.

He has been involved as Principal Investigator, Scientific Committee member, Steering Committee member, or member of Data Safety Monitoring Board in multiple international, multicenter randomized trials in thrombosis. He is a Steering Committee member of the NHLBI BRIDGE and Kids DOTT studies and the CIHR PAUSE trial, He is a founding member of ATLAS, a US-based ARO-CRO in thrombosis-related research. He is a panel member of a US national experts consensus group for clinical excellence in thrombosis management, a member of the Anticoagulation Forum and the Thrombosis/Haemostasis Society of North America, co-Chair of the Scientific Standardization Committees of Predictive Variables and Perioperative Thrombosis and Haemostasis as part of the International Society of Thrombosis and Haemostasis, and co-author for the 8th and 9th American College of Chest Physician (ACCP) Antithrombotic Guidelines, the 2008 International Consensus Statement Guidelines and senior author for the 2013 International Consensus Statement on venous thromboembolic disease. He was reviewer for the 2014 ESC Guidelines on Pulmonary Embolism. He is presently a panelist for the 2016/2017 ACCP Antithrombotic Guidelines on Perioperative Anticoagulant Management.

Dr. Spyropoulos’ articles, letters, and editorials have been published in over 160 peer-reviewed journals including The New England Journal of Medicine, Blood, Circulation, American Journal of Hematology, American Journal of Medicine, Chest, Thrombosis Haemostasis, American Journal of Cardiology, Journal of Thrombosis and Haemostasis , Journal of the American College of Cardiology, Clinical Applied Thrombosis Haemostasis, and Thrombosis Research. He is Section Editor for Thrombosis and Haemostasis, and is on the editorial staff for Thrombosis Research and Hospital Medicine. He is a reviewer for many journals.

Research Focus

Dr. Spyropoulos has helped to develop disease management using LMWH in outpatient-based treatment of venous thromboembolic disease, patient self-testing of warfarin, perioperative heparin “bridging” for patients on chronic anticoagulation, medical inpatient thromboprophylaxis, protocols with the use of anticoagulants for HIT, and clinical use of the novel oral anticoagulants, including their use in special patient populations. Dr. Spyropoulos is active in assessing outcome and pharmacoeconomic analyses of these protocols and has lectured extensively both nationally and internationally on these issues.

Medical inpatient thromboprophylaxis

It is estimated that there are over 8 million hospitalized acutely ill hospitalized medical patients in the US alone who may be at risk of venous thromboembolism (VTE). Effective and safe extended thromboprophylaxis continues to elude clinicians, and three large randomized trials studying over 20,000 patients with anticoagulant therapy in the post-hospital discharge period failed to convincingly show a net clinical benefit in favor of pharmacologic thromboprophyaxis.

Dr. Spyropoulos’ research has focused on the development and validation of both clinical VTE and bleeding risk assessment models using individual clinical risk factors that are weighted and scored (the IMPROVE VTE and Bleed risk models). Along with other researchers,  Dr. Spyropoulos has done work in assessing whether potential biomarkers such as the Dd or pro-BNP can also assist in identifying high VTE risk cohorts from the medically ill population.

Dr Spyropoulos is the co-Chair of the Executive Committee for MARINER, an 8000 patient global Phase 3 multicenter study of extended thromboprophylaxis in hospitalized medically ill patients with rivaroxaban, an oral direct FXa inhibitor He was instrumental in development of the study protocol, which for the first time is utilizing both the IMPROVE VTE risk assessment model as well as the Dd as tools to identify a high risk cohort of this patient group that may benefit for the first time from a strategy of extended post-hospital discharge thromboprophylaxis.

Perioperative heparin bridging therapy

It is estimated that ~ 1 in 10 patients on chronic oral anticoagulant therapy are being assessed annually in periprocedural indications, or approximately 500,000 patients a year in the US. The optimal perioperative anticoagulant management of these patients remains uncertain. It was common to use heparin bridging therapy during temporary interruption of warfarin to sustain a potential beneficial anticoagulant effect in the periprocedural period. Dr Spyropoulos conducted extensive background work in this field, including multicenter prospective cohort outcome studies of periprocedural bridging therapy. He and his colleagues of BRIDGE investigators obtained NIH funding to conduct for the first time a placebo-controlled randomized trial of heparin bridging therapy, the BRIDGE Study. The study results were published in the New England Journal of Medicine in 2015. This landmark trial revealed for the first time proof-of-concept that paradoxically a strategy of heparin bridging therapy in patients with atrial fibrillation on chronic warfarin needing temporary interruption of their warfarin for an elective procedure or surgery did not reduce post-operative thromboembolic risk but led to a two-to-three fold increased risk of post-operative major bleeding. Further studies are underway to expand on this concept of harm and failure to prevent arterial thromboembolic events with a heparin-based anticoagulant strategy in the periprocedural period. This includes a potential application to the NIH for a BRIDGE-2 placebo controlled study in the higher risk mechanical heart valve population that need temporary interruption of warfarin for an elective procedure or surgery.


University of Pennsylvania College of Arts and Sciences, Philadelphia, PA
Degree: BA
Field of Study: Biological Basis of Behavior

University of Pennsylvania School of Medicine, Philadelphia, PA
Degree: MD
Field of Study: University Scholar

Honors and Awards

2004 Lovelace Clinic Foundation Excelllence in Education Award, Albuquerque, NM USA
2002 Honored Member – Strathmore’s Who’s Who 2001-2002 addition
1990 Fox Chase Cancer Center Award, Guest scholar at Oxford University, England

  1. Raskob GE, Spyropoulos AC, Zrubek J, Ageno W, Albers G, Elliott CG, Halperin J, Haskell L, Hiatt WR, Maynard GA, Peters G, Spiro T, Steg G, Suh EY, Weitz JI. “The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of venous thromboembolism: Design, rationale, and clinical implications.” Thromb Haemost 2016; Feb 4;115(5).
  2. Zahid MF, Murad H, Litzow MR, Hogan WJ, Patnaik MS, Khorana A, Spyropoulos AC, Hashmi SK, “Venous thromboembolism following hematopoietic stem cell transplantation – a systematic review and meta-analysis.” Ann Hematol 2016; April 22 [Epub ahead of print].
  3. Kittleson J, Steg PJ, Halperin J, Goldenberg NA, Schulman S, Spyropoulos AC, Kesssler CM, Turpie AGG, Cutler NR, Hiatt WR, as the Antithrombotic Trials Leadership and Steering (ATLAS) Group. “Bivariate evaluation of thrombosis and bleeding risk: An application to clinical trials of non Vitamin K oral anticoagulants for stroke prevention in atrial fibrillation.” Thromb Haemost 2016 (in press).
  4. Douketis JD, Healy JS, Brueckmann M, Fraessdorf M, Spyropoulos AC, Wallentin L, Oldgren J, Reilly P, Ezekowitz MD, Connolly SJ, Yusuf @, Eikelboom JW. “Urgent surgery or procedures in patients taking dabigatran or warfarin: analysis of perioperative outcomes from the RE-LY trial.” Thromb Res 2016; 139: 77-81.
  5. Nazha B, Spyropoulos AC. “The BRIDGE trial: what a hospitalist should know.” J Hosp Med 2016 Apr 21. doi: 10.1002/jhm.2594. [Epub ahead of print].
  6. Spyropoulos AC, Al-Badri A, Sherwood MW, Douketis JD. “Periprocedural management of patients on a vitamin K antagonist or a direct oral anticoagulant requiring an elective procedure or surgery.” J of Thromb Haemost 2016; Mar 14. doi: 10.1111/jth.13305. [Epub ahead of print].
  7. Greene MT, Spyropoulos AC, Chopra V, Grant PJ, Kaatz S, Bernstein SJ, Flanders SA. “Derivation and validation of risk assessment models of venous thromboembolism in hospitalized medical patients.” Am J Med 2016; Apr 20 doi: 10.1016/j.amjmed.2016.03.031. [Epub ahead of print] .
  8. Rosenberg DJ, Press A, Fishbein J, Lesser M, McCullagh L, McGuinn T, Spyropoulos AC “External validation of the IMPROVE bleeding risk assessment model in medical patients.” Thromb Haemost 2016 (in press)
  9. Grottke O, Aisenberg J Bernstein R, Goldstein P, Huisman MV, Jamieson DG, Levy JH, Pollack, Jr, CV, Spyropoulos AC, Steiner T, del Zoppo GJ, Eikelboom J. “Efficacy of prothrombin complex concentrates for the emergency reversal of dabigatran-induced anticoagulation.” Critical Care 2016; Apr 28;20(1):115. doi: 10.1186/s13054-016-1275-8.
  10. Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, Garcia DA MD, Alan Jacobson A, Jaffer AK, Kindzelski A, Kong DF, Schulman S, Turpie AGG, Hasselblad V, Ortel TL, for the BRIDGE Investigators. “Perioperative bridging anticoagulation in patients with atrial fibrillation.” N Engl J Med 2015; 373(9): 823-33.
  11. Douketis JD, Healy JS, Bruekmann M, Eikelboom JW, Ezekowitz MD, Fraessdorf M, Noack H, Oldgren J, Reilly P, Spyropoulos AC, Wallentin L, Connolly SJ. “Perioperative bridging anticoagulation During dabigatran or warfarin interruption among patients in the RE-LY trial who had an elective surgery or interruption.” Thromb Haemost 2015; 113(3):625-32
  12. Mahan CE, Fields LE, Mills RM, Stephenson JJ, Fu AC, Fisher M, Spyropoulos AC. “All-cause mortality and use of antithrombotis within 90 days of discharge in acutely ill medical patients.” Thromb Haemost 2015; 114(4); 685-94.
  13. Francis C, Kessler C, Goldhaber SZ, Kovacs M, Monreal M, Huisman MV, Bergqvist D, Turpie AGG, Ortel T, Spyropoulos AC, Pabinger-Fasching I Kakkar A. “Treatment of venous thromboembolism in cancer patients with dalteparin for up to twelve months: The DALTECAN Study.” J of Thromb Haemost 2015; 13(6):1028-35.
  14. Mathew JG, Spyropoulos AC, Yusuf A, Vincent J, Eikelboom J, Shestakovska O, Fremes S, Noora J,Guo L, Peterson M, Patel A, Schulman S, Pai M, Whitlock R. “Efficacy and safety of early parenteral anticoagulation as a bridge to warfarin after mechanical valve replacement.” Thromb Haemost 2014; Aug 28;112(6):1120-8.
  15. Sherwood M, Douketis J, Patel MR, Piccini J, Hellkamp AS, Lokhnygina, Hankey G, Sinfer DE, Nessel CC, Spyropoulos AC, Mahaffey K, Fox KAA, Califf R, Becker R. “Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: Results from ROCKET AF.” Circulation 2014; 129(18):1850-9.

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