Two different mechanisms in patients with venous thrombosis and defective fibrinolysis : low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor INGA MARIE

Fibrinolytic components after venous occlusion and concentrations of tissue plasminogen activator inhibitor were studied in 100 consecutive patients with confirmed recurrent deep vein thrombosis or pulmonary embolism. After 20 minutes of venous occlusion the fibrinolytic response was decreased in 33 patients, as measured both amidolytically with S-2251 and on fibrin plates. Two different mechanisms responsible for the poor fibrinolytic response could be distinguished. Twenty two of the patients in whom the response was poor released normal amounts of tissue plasminogen activator antigen, as assayed by immunoradiometric assay, but had appreciably increased concentrations of tissue plasminogen activator inhibitor. The 11 other patients in whom the response was poor had both low tissue plasminogen activator activities and low tissue plasminogen activator antigen concentrations but normal concentrations of tissue plasminogen activator inhibitor. The results show not only that defective synthesis or release of tissue plasminogen activator may be important in the pathogenesis of venous thrombosis but also that a large group of patients with thrombosis have an increased concentration of the inhibitor to tissue plasminogen activator. Department for Coagulation Disorders, University of Lund, General Hospital, S-214 01 Malmo, Sweden INGA MARIE NILSSON, MD, professor LILIAN TENGBORN, MD, senior physician Department of Surgery, University of Lund HARALD LJUNGNtR, MD, senior physician Correspondence to: Dr I M Nilsson. Introduction In the complex pathogenesis of venous thrombosis one important factor promoting the development of venous thrombosis is a defective fibrinolytic system. This system is activated by various agents, an important one being the tissue type plasminogen activator, localised to the vessel wall. It is well known that many patients with recurrent idiopathic venous thrombosis have defective fibrinolytic systems-that is, decreased vessel wall fibrinolysis or defective release of activators after venous occlusion tests, or both.' 8 The role of fibrinolytic inhibitors in association with venous thrombosis was first described in 1961.9 Since then several studies have dealt with different inhibitors and their role in the disease. A new rapid inhibitor to tissue plasminogen activator has been identified,'0-3 but its physiological importance in patients with thrombosis is less well understood. We aimed therefore to study both the fibrinolytic components in postocclusion plasma and the tissue plasminogen activator inhibitor in patients with recurrent deep venous thrombosis. Subjects and methods We studied 60 men and 40 women, aged 14-70 (mean 43) years, who had been referred because of recurrent deep venous thrombosis or pulmonary embolism without any other known diseases. All the patients were investigated at least three months after their latest thrombotic episode. Diagnosis was always verified by phlebography or pulmonary scintigraphy and angiography. At the time of investigation 73 of the patients were taking vitamin K antagonists. Fifty seven volunteers (policemen, doctors, nurses, office workers, mechanics, and technicians) aged 20-60 (mean 33) years, of whom 27 were women, served as controls. All were apparently healthy, and none had any history of superficial thrombophlebitis, deep venous thrombosis, or any other disease in which thrombosis is commonly a complicating factor. None of the female controls was taking a contraceptive drug. Controls and patients were studied in parallel. 1453 BRITISH MEDICAL JOURNAL VOLUME 290 18 MAY 1985