Thrombosis-New Developments from the Lab to the Clinic

By Stephanie L. Perry, M.D. and Thomas L. Ortel, M.D., Ph.D.

Hematologists are now more than ever playing an important role in the diagnosis, treatment, risk-stratifica- tion and prevention of patients with venous as well arterial thromboembolic disorders. To fill this increasing need for the most current clinical knowledge and to get a glimpse at ongoing research, there will be two different Education Programs, as well as a Scientific Committee Session on thrombotic disorders, given today.

In the first Education Program, entitled Thombotic Disorders: Diagnosis and Treatment, that will be given today from 8:00 a.m. - 9:45 a.m. and again from 4:15 p.m. - 6:00 p.m., four speakers will review topics important for clinicians.

Dr. Andrew Schafer will begin with an overview of the genetic and acquired factors known to be risk factors for thrombosis. The explosion of information in this area has raised many questions con- cerning the use of this information in the management of individual patients. The next two speakers at this session will focus on two unique patient populations. Dr. Mark Levine will address the special problems related to the treatment of thrombosis in patients with cancer and the concern of catheter-related thrombosis in this patient population. Dr. Barbara Konkle will then enlighten the audience on special considerations for the risk factors, diagnosis, and management for thrombosis in the pregnant patient. The final speaker, Dr. Clive Kearon, will review the "risks and benefits" of anticoagulation in patients at high risk for arterial and/or venous thromboembolic events in the peri-operative setting. Algorithms for both pre- and post-operative management will be outlined, including when to consider "bridging therapy."

The second Education Program, entitled Consultations on Patients with Venous or Arterial Disease, will be given from 10:15 a.m. - noon (and again on Sunday, December 7th from 7:30 a.m. - 9:15 a.m.). During this program, greater emphasis will be placed on the newer anticoagulation agents and on the diagnosis and treatment of arterial disease. In this way the two programs will complement each other. Dr. Charles Francis will begin the session with a review of the newer anticoagulant agents, including the specific factor Xa inhibitor fondaparinux, and the direct thrombin inhibitors hirudin, argatroban, bivalirudin, and ximelagatran. His discussion of these agents will include (1) structure and site of action, (2) pharmacokinetics, (3) dosing and administration recommendations, (4) therapeutic monitoring, and (5) approved prophylactic and therapeutic indications established by clinical trial data. Dr. William Hiatt will then outline the approach to evaluating and medically managing patients with peripheral arterial disease. Medical management will focus on risk factor modification and therapeutic interventions, specifically antiplatelet agents. This will be followed by an update by Dr. Mark Jackson on the interventional approaches to thrombosis, including the use of retrievable vena cava filters, thromboembolectomy, and a discussion of thrombolytic therapy.

In addition to these two Educational Programs, the Scientific Committee Session on Thrombosis and Vascular Biology, Targeting the Endothelium for Good and Bad, will delve deeper into the basic science aspects that may help unravel some of the mysteries of why our patients have thrombotic events, and how potential treatments may prove beneficial. Dr. William Aird will present his findings of thrombin-responsive transcriptional networks in endothelial cells. Next, Dr. Robert Kerbel will detail his work on overcoming the obstacles of implementing and monitoring angiogenic inhibitors in order to achieve a favorable response in cancer patients with minimization of the "high frequency of thrombotic events." Finally, Dr. John Griffin will present his work evaluating the potential role of recombinent activated protein C in directly protecting endothelial cells as a mechanism of reduced mortality in patients with severe sepsis. This session will be given today at 10:15 a.m. - noon and again on Sunday, December 7th, from 7:30 a.m. - 9:15 a.m.