Niels Tromholt

In vivo demonstration of focal fibrinolytic activity in abdominal aortic aneurysms

Disseminated intravascular coagulation in association with arterial aneurysm has been reported in several cases. Reports have suggested a continuous deposition of fibrin and/or platelets at the site of the aneurysm followed by fibrinolysis as responsible for this disorder. To further investigate this theory we studied the in vivo binding of an indium-111-labelled monoclonal antibody against human tissue plasminogen activator (t-PA), a proteolytic enzyme involved in the fibrinolysis. Six patients admitted to the hospital for elective resection of an abdominal aortic aneurysm with a mural thrombus were examined. One day before the operation the antibody was injected intravenously. Scintigrams acquired just prior to operation and tissue samples obtained at the operation revealed an increased t-PA accumulation in the wall of the aneurysm. The study demonstrates in vivo, focally increased fibrinolytic activity in the aneurysm, explaining the coagulopathy observed in these patients.

Detection of deep venous thrombosis with indium 111-labelled monoclonal antibody against tissue plasminogen activator

The administration of a radiolabelled monoclonal antibody against tissue plasminogen activator allows detection of areas with increased fibrinolytic activity, i. e. those with an active thrombotic lesion. Eight patients with phlebographically verified deep venous thrombosis were examined. At the time of immunoscintigraphy study they were examined receiving anticoagulant therapy. Some 75–85 MBq indium 111-labelled antibody were injected, and scintigrams were obtained after 30 min and after 24 h. The precise site of the thrombus could not be visualized after 30 min due to high background activity, whereas after 24 h it was detectable in all patients. The thrombus/background ratios achieved are twice as high as those observed in a human antifibrin antibody study. These preliminary data suggest a high sensitivity of our t-PA-specific antibody for the detection of active deep venous thrombosis in man, and our antibody seems to offer theoretical advantages over both platelet and fibrin-specific antibodies.