Nearly 2 million Americans a year experience the painful swollen extremities associated with deep venous thrombosis (DVT). A thrombus - or blood clot - forms mainly in the deep veins of the lower leg or thigh and interferes with circulation. If the clot breaks loose, it can migrate to the lungs and block a pulmonary artery, resulting in a life-threatening pulmonary embolism.
Traditional treatment for DVT has been with the use of anticoagulation drugs alone, but physicians in Emory University's Division of Vascular Surgery and Endovascular Therapy are participating in a clinical trial to demonstrate the effectiveness of anticoagulation treatment when combined with thrombolytic therapy - a procedure using medication delivered through a catheter, or tube threaded through the veins, that completely dissolves the blood clots.
"Solely using anticoagulation treatment often only prevents further clot formation," says Emory vascular surgeon and principal investigator Karthikeshwar Kasirajan, MD. "Since the actual clot isn't removed, it may still lead to significant discomfort, leg swelling, as well as skin ulcers within two to five years. Unfortunately if the clots are not immediately removed, the resulting valvular damage and vein obstruction is usually permanent."
The $4.2 million clinical trial will include 20 - 30 hospitals nationwide and is being directed by the Jobst Vascular Center. The TOLEDO study (Thrombosis of Lower Extremity DVT Or anticoagulation) is funded by Abbott Laboratories of Illinois.
Researchers hope to recruit up to twenty eligible patients who have currently experienced the symptoms of DVT for less than a month to participate in the clinical trial. During two days of hospitalization, the patient will be administered the thrombolytic agent, urokinase. Urokinase is currently being used for dissolving clots in patients with heart attacks.
Using a catheter less than two millimeters wide, the urokinase is injected directly into the clot. The thrombolytic therapy is followed by anticoagulation medication for six months to prevent recurrent clot formation. Patients will be required to have periodic follow-up appointments for up to one year.
Although less than two percent of patients who receive clot dissolving medication run a risk of bleeding complications, patients with certain risk factors are not eligible to participate in the study. For example, patients with a history of peptic ulcer bleeding or recent surgery will not be considered appropriate candidates for this therapy.
"DVT was traditionally treated solely with anticoagulants, such as coumadin, because there was a lack of understanding of the long-term effects of venous damage," says Ross Milner, MD, another Emory vascular surgeon involved in the trial. "These risks include persistent leg swelling and discomfort, skin discoloration, chronic skin ulcers, and recurrent clot formation in the leg."
By using catheter-directed thrombolysis, researchers hope to reduce or eliminate the immediate symptoms of DVT, reduce or avoid late consequences, and prevent pulmonary embolism. The latter condition, which is potentially fatal, occurs when a large clot breaks off and travels to the lung.
Dr. Elliot Chaikof, a member of the investigative team, notes that thrombus removal for DVT has several advantages. It rapidly removes the clot, restores venous flow, preserves valvular function, and decreases the risk of developing postphlebitic syndrome.
"The result is a much more rapid and effective removal of the thrombus," Dr. Chaikof explains. "The down time for the patient is much shorter with treatment lasting a couple of hours instead of days."
The study will also consider how early clot lysis is associated with a patient's quality of life.