The fibrinolytic effects of intermittent pneumatic compression: mechanism of enhanced fibrinolysis.
OBJECTIVE
Intermittent pneumatic compression (IPC) is an effective form of deep vein thrombosis prophylaxis for general surgery patients. The antithrombotic effect of IPC is thought to be the result of increased venous velocity and stimulation of endogenous fibrinolysis. However, the mechanism of enhanced fibrinolytic activity and the relative effects on normal and postthrombotic veins have not been defined. The purposes of this study are 1) to quantify changes in fibrinolytic activity with IPC; 2) to study the mechanism of fibrinolytic enhancement with IPC; and 3) to evaluate whether postthrombotic patients have the same capacity for fibrinolytic enhancement with IPC as do normal subjects.


METHODS
Twelve volunteers (6 normal and 6 postthrombotic) had 5 IPC devices applied for 120 minutes in random fashion, 1 per week x 5 weeks. The devices included single-chamber, sequential, foot, calf, and long-leg compression. Subjects had an indwelling antecubital venous cannula placed for blood drawn at baseline, 60, 120, and 180 minutes after IPC devices were applied. Global fibrinolytic activity (euglobulin fraction, fibrin plate assay), tissue plasminogen activator (tPA) antigen (Ag) and activity (Act), plasminogen activator inhibitor-1 (PAI-1) Ag and Act, alpha-2-antiplasmin-plasmin complexes, and von Willebrand factor (vWF) antigen were assayed.


RESULTS
A striking elevation in fibrinolytic activity was noted at 180 minutes with all devices in normal subjects and postthrombotic patients (p = 0.01-0.0001); however, baseline and stimulated fibrinolytic activity was attenuated in postthrombotic patients (<0.03). The tPA-Act increased only in normal subjects (3.8 +/- 1.9%) (p = 0.057), despite a decrease in plasma tPA-Ag, which was observed in both normal subjects (-12.4 +/- 3.8%) (p = 0.009) and patients (-17.2 +/- 3.1%) (p = 0.001). PAI-1-Ag decreased in both normal subjects (-13.4 +/- 3.8%) (p = 0.007) and patients (-12.0 +/- 3.1%) (p = 0.013) with a marked reduction in PAI-1-Act in both normal subjects (p = 0.003) and patients (p = 0.004). There were no changes in vWF, and alpha-2-antiplasmin-plasmin complexes increased only in postthrombotic patients (p = 0.021).


CONCLUSIONS
Stimulation of endogenous fibrinolytic activity occurs after IPC, both in normal subjects and postthrombotic patients; however, baseline and overall fibrinolytic response in postthrombotic patients is reduced. The mechanism of increased fibrinolytic activity is likely because of a reduction in PAI-1, with a resulting increase of tPA activity.
Comerota
A J
AJ
Department of Surgery, Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Chouhan
V
V
Harada
R N
RN
Sun
L
L
Hosking
J
J
Veermansunemi
R
R
Comerota
A J
AJ
Schlappy
D
D
Rao
A K
AK
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015908:Counterpulsation / Q000295:instrumentation; D005260:Female; D005341:Fibrinolysin / Q000032:analysis; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011312:Pressure; D013924:Thrombophlebitis / Q000097:blood / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000097:blood; D000979:alpha-2-Antiplasmin / Q000032:analysis; D000511:alpha-Macroglobulins / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin