Prospective double-arm study of fibrinolysis in surgical patients

During surgery, the balance between thrombosis and fibrinolysis is altered. Methods reported to increase fibrinolysis, such as compression devices, may reduce venous thrombosis. However, there are no prospective studies comparing methods and the effect on fibrinolysis.

In a prospective study, general surgical patients were randomized to either sequential compression devices (Group 1) or subcutaneous heparin (Group 2), and fibrinolysis factors were measured in order to determine the effect on the fibrinolysis system. Blood samples were drawn at a similar time of the day with the tourniquet off. Specifically, t-PA antigen, plasminogen activator inhibitor-1 (PAI-1), and D-dimer were measured preoperatively (preop) and on Postoperative Days (POD) 1 and 7 by the ELISA method. Fibrinolysis factors were reported as the mean +/- SD and as percentage change from preoperative 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. Nonambulatory patients were excluded from the study and DVT prophylaxis methods were initiated at surgery and used through POD 2.

For the 136 patients in the study, there were no differences in clinical characteristics such as age, surgical time (all > 60 min), anesthesia type (general or spinal), type of surgical procedure, or other risk factors for DVT. Two DVTs occurred at POD 1 and 30 (both Group 2), and one pulmonary embolism in each group (POD 7 for Group 1; POD 1 for Group 2). For subjects without thrombosis, D-dimer changes were parallel for both groups, increasing through POD 7. Similarly, t-PA antigen levels rose from baseline on POD 1 in both groups, with a return toward baseline by POD 7. The PAI-1 levels increased on POD 1 in both groups, but severalfold more in Group 1 (compression devices). The elevation in PAI-1 decreased by 50% in Group 1 by POD 7, while values returned to normal in Group 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.

This is the first report of a prospective, randomized comparison 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 showed 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 work in parallel, the marked elevation of PAI-1 on POD 1 (although only slightly above reference values) and continuing into POD 7 for subjects using compression devices requires further inquiry. The elevation of PAI-1 in the face of elevated t-PA and D-dimer has been reported, but the comparison between patients using sequential compression devices and mini-dose heparin has not been reported. The reason for the elevation requires additional study into other influences on the synthesis, secretion, and/or function of PAI-1 that do not affect t-PA.