PROSPECTIVE DOUBLE-ARM STUDY OF FIBRINOLYSIS IN SURGICAL PATIENTS

Background. During surgery, the balance between thrombosis and fibrino lysis is altered. Methods reported to increase fibrinolysis, such as c ompression devices, may reduce venous thrombosis. However, there are n o prospective studies comparing methods and the effect on fibrinolysis . Materials and methods. In a prospective study, general surgical pati ents were randomized to either sequential compression devices (Group 1 ) or subcutaneous heparin (Group 2), and fibrinolysis factors were mea sured in order to determine the effect on the fibrinolysis system. Blo od samples were drawn at a similar time of the day with the tourniquet off. Specifically, t-PA antigen, plasminogen activator inhibitor-1 (P AI-1), and D-dimer were measured preoperatively (preop) and on Postope rative Days (POD) 1 and 7 by the ELISA method. Fibrinolysis factors we re reported as the mean +/- SD and as percentage change from preoperat ive values. Noninvasive vascular studies were performed preop, and on POD 1, 7, and 30, by an examination of the infrainguinal venous system and external iliac veins in bilateral lower extremities. Nonambulator y patients were excluded from the study and DVT prophylaxis methods we re initiated at surgery and used through POD 2. Results. For the 136 p atients in the study, there were no differences in clinical characteri stics such as age, surgical time tall >60 min), anesthesia type (gener al or spinal), type of surgical procedure, or other risk factors for D VT. Two DVTs occurred at POD 1 and 30 (both Group 2), and one pulmonar y embolism in each group (POD 7 for Group 1; POD 1 for Group 2). For s ubjects without thrombosis, D-dimer changes were parallel for both gro ups, increasing through POD 7. Similarly, t-PA antigen levels rose fro m baseline on POD 1 in both groups, with a return toward baseline by P OD 7. The PAI-1 levels increased on POD 1 in both groups, but severalf old more in Group 1 (compression devices). The elevation in PAI-I decr eased by 50% in Group 1 by POD 7, while values returned to normal in G roup 2. These changes were not significant using the Mann-Whitney test . Only three patients had thrombotic episodes so that data on changes in fibrinolysis factors are difficult to compare with the larger group . Conclusions. This is the first report of a prospective, randomized c omparison of fibrinolysis factors using sequential compression devices in comparison to low dose unfractionated heparin in general surgical patients, and comparing postoperative values to preop. Both groups sho wed an enhanced fibrinolysis by elevation in t-PA antigen and D-dimer on POD 1, as expected when fibrinolysis occurs. While PAI-1 and t-PA w ork in parallel, the marked elevation of PAI-1 on POD 1 (although only slightly above reference values) and continuing into POD 7 for subjec ts using compression devices requires further inquiry. The elevation o f PAI-1 in the face of elevated t-PA and D-dimer has been reported, bu t the comparison between patients using sequential compression devices and mini-dose heparin has not been reported. The reason for the eleva tion requires additional study into other influences on the synthesis, secretion, and/or function of PAI-1 that do not affect t-PA. (C) 1998 Academic Press.