Division of Cardiovascular Diseases Strategic Plan

Goals in Cardiovascular Clinical Problems or Disease States

2.2i. Improve diagnosis, prevention, and treatment of venous thromboembolism

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Venous thromboembolism (VTE) refers to the disorders of deep vein thrombosis (DVT) and pulmonary embolism (PE) that commonly occur together and should be thought of as a continuum for purposes of diagnosis and follow-up. The annual U.S. incidence of VTE is 250,000. Health consequences of VTE can be severe, including death from PE, recurrence of VTE, and chronic morbidity from post-phlebitic syndrome. Of individuals with proximal DVT (affecting the popliteal, femoral or iliac veins), 50 percent have PE and it is fatal in 10 percent. Calf DVT carries a low risk (1 percent) of clinically significant PE but, if left untreated, extends proximally in 15-25 percent of cases. Even with appropriate treatment, rates of chronic venous insufficiency (post-phlebitic syndrome) are as high as 25 percent within 2 years of proximal DVT. The classic triad of VTE risk factors described by Virchow in the 19th century still applies: venous stasis, activation of blood coagulation, and venous wall injury. This goal will be advanced by understanding the complexity of thrombotic and antithrombotic factors within the venous circulation under normal conditions and how their balance is perturbed under abnormal circumstances, such as prolonged immobility.

Strategies to Accomplish this Goal May Entail:

Basic Research:

  • Investigate mechanisms and time course of venous valve damage associated with DVT, and how to preserve and/or replace valvular function.
  • Investigate cellular (platelet, red blood cell, leukocyte, endothelial cells), rheological, and molecular mechanisms of venous clot formation, extension, and stabilization.
  • Investigate whether there are genetic or other predispositions for “idiopathic” DVT.
  • Identify potential new oral anticoagulants.
  • Investigate the roles of inflammation and venous endothelial damage in pathogenesis of DVT.
  • Identify biomarkers of DVT with greater sensitivity and specificity than those currently available.

Translational Research:

  • Examine the preventive value of routine work-ups for thrombophilia: investigate whether “impending” or early DVT has a proteomic signature.
  • Improve the resolution and techniques of imaging venous vessels, particularly in areas now difficult to assess, such as pelvic veins. Replace contrast venography with less invasive, less painful, and less toxic imaging technology.
  • Facilitate the development of targeted imaging agents that show promise in detection of venous thrombus.
  • Facilitate the development of novel thrombolytic agents that directly attach and destroy the thrombus (e.g., by using nanotechnology).

Clinical Research:

  • Compare the outcomes of different regimens that include standardized external compression, exercise, leg elevation, and/or behavioral interventions, in addition to standard anticoagulation after lower extremity DVT.
  • Compare immediate, local, catheter-directed thrombolysis to standard care for lower extremity DVT.
  • Determine the utility of vena caval filters over the long-term in patients with contraindications to anticoagulation.
  • Determine the optimum times for removal of newer, non-permanent vena caval filters.
  • Determine the true prevalence and long-term outcomes of VTE.
  • Determine the optimal duration for anticoagulation post idiopathic DVT.
  • Develop physician and patient education to initiate proven methods of prophylaxis in all subjects at risk, including surgical patients and those with various chronic medical illnesses.

Contributing Sources:

September 2008

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