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The fibrinolytic effects of intermittent pneumatic compression: mechanism of enhanced fibrinolysis.

BACKGROUND AND OBJECTIVES: 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.

Adult↗

Home use of impulse compression of the foot and compression stockings in the treatment of chronic venous insufficiency.

PURPOSE: The use of intermittent pneumatic compression, in addition to elastic bandages or stockings, accelerates the healing of leg ulcers in patients with severe chronic venous insufficiency (CVI). There is recent evidence that impulse compression of the plantar venous plexus reduces post-traumatic ankle swelling and prevents postoperative venous thromboembolism. The purpose of this study was to evaluate the clinical and hemodynamic responses after home use of impulse foot compression for 3 months in patients already using therapeutic compression stockings for the management of CVI. METHODS: Twelve extremities from 9 patients with documented CVI, class 4 to 5 according to the Clinical, Etiology, Anatomy, Pathophysiology classification system, were included in this prospective cohort study. All patients were instructed to use a foot pump device at home for 2 hours a day for 3 months in addition to therapeutic compression stockings (30-40 mm Hg) worn during the day. The device was set to three cycles (3 seconds) of compression (120 mm Hg) per minute. A clinical scoring system was completed before foot compression and 1, 2, and 3 months thereafter. In addition, all patients underwent air plethysmography studies at the same time intervals, including venous volume, venous filling index, ejection fraction, and residual volume fraction. RESULTS: Patients reported significant improvement in their scores for swelling (P <.05) and pain (P <.04). Air plethysmography showed a reduction in venous volume and venous filling index, although these differences were not significant. Ejection fraction remained unchanged and residual volume fraction was significantly reduced (P <.05) compared with baseline. The foot compression devices were well tolerated by all the patients in the study. CONCLUSIONS: The use of home foot impulse compression plus elastic stockings significantly reduced the residual volume fraction as measured by air-plethysmography in a group of patients with severe CVI. This favorable hemodynamic response could, in part, explain the clinical improvement achieved by this combined treatment. However, this represents a preliminary pilot study that needs to be confirmed in future randomized controlled studies with more patients included.

Bandages↗

An in vitro cell culture system to study the influence of external pneumatic compression on endothelial function.

PURPOSE: External pneumatic compression (EPC) is an effective means of prophylaxis against deep venous thrombosis. However, its mechanism remains poorly understood. Understanding of the biological consequences of EPC is an important goal for optimizing performance of the EPC-generating device and providing guidance for clinical use. We present a new in vitro cell culture system (Venous Flow Simulator) that simulates blood flow and vessel collapse conditions during EPC, and we examine the influence of these factors on endothelial cell (EC) fibrinolytic activity and vasomotor function. METHODS: An in vitro cell culture system was designed to replicate the hemodynamic shear stress and vessel wall strain associated with induced blood flow during different modes of EPC. Human umbilical vein endothelial cells were cultured in the system and subjected to intermittent flow, vessel collapse, or a combination of the two. The biologic response was assessed through changes in EC morphology and the expression of fibrinolytic factors tissue plasminogen activator, plasminogen activator inhibitor type 1, profibrinolytic receptor (annexin II), and vasomotor factors endothelial nitric oxide synthase and endothelin-1. RESULTS: The cells remained attached and viable after being subjected to intermittent pulsatile flow (F) and tube compression (C). In F and F + C, cells aligned in the direction of flow after 6 hours. Northern blot analysis of messenger RNA shows that there is an upregulation of tissue plasminogen activator expression (1.95 +/- 0.19 in F and 2.45 +/- 0.46 in FC) and endothelial nitric oxide synthase expression (2.08 +/- 0.25 in F and 2.11 +/- 0.21 in FC). Plasminogen activator inhibitor type 1, annexin II, and endothelin 1 show no significant change under any experimental conditions. The results also show that pulsatile flow, more than vessel compression, influences EC morphology and function. CONCLUSION: Effects on ECs of intermittent flow and vessel collapse, either individually or simultaneously, were simulated with an in vitro system of new design. Initial results show that intermittent flow associated with EPC upregulates EC fibrinolytic potential and influences factors altering vasomotor tone. The system will facilitate future studies of EC function during EPC.

Blood Flow Velocity↗

A clinical comparison of pneumatic compression devices: the basis for selection.

PURPOSE: The five pneumatic compression devices (PCDs) that are marketed provide mechanical protection from deep venous thrombosis (DVT). They differ with respect to patterns of compression and the length of the sleeve. Evidence linking differences to clinical outcomes is lacking. Our purpose was twofold: to evaluate each of the marketed PCDs with respect to effectiveness, compliance, and patient and nursing satisfaction and to determine whether there is a clinical basis for the selection of one device over another. METHODS: Each of the marketed devices was used exclusively for a 4-week period. Patients participated in an evaluation including venous duplex ultrasound scan, DVT risk assessment, and device evaluation. Vascular laboratory records were used to document DVT. Compliance was measured by meters installed on all pumps. A ranking matrix was stratified by compression pattern: rapid graduated sequential compression, graduated compression, and intermittent compression, and each device was rated by patients and nurses. RESULTS: The PCDs were used in 1350 cases with a DVT rate of 3.5% ranging from 2% to 9.8% depending on the method of compression. Patients with DVT were older (58 vs 54 years), had better compliance (67% vs 50%), and had more compression days (11 vs 7.2). When thigh-length sleeves were used, a greater proportion of DVT occurred in the proximal segments (71%) as compared with the number of proximal DVT when the calf-length devices were used (52%; P =.21). Devices W, X, and Y had comparable rates of DVT, which were lower than those for V and Z. Compression device W, [correction] with calf and thigh sleeves, achieved the best overall ranking largely because of high scores for patient and nurse satisfaction. CONCLUSION: Our data appear at odds with commonly held beliefs. We were unable to show a difference in DVT incidence based on the length of the device or the method of compression. Randomized studies are needed to confirm our findings and evaluate hypotheses derived from this study.

Bandages↗

Intermittent pneumatic compression effect on eccentric exercise-induced swelling, stiffness, and strength loss.

OBJECTIVE: The purpose was to determine if intermittent pneumatic compression (IPC) affects muscle swelling, stiffness, and strength loss resulting from eccentric exercise-induced injury of the elbow flexors. We hypothesized that the compression would decrease swelling and stiffness. DESIGN: Repeated measures design with a before-after trial comparison within each day. SETTING: Conducted at a university Somatic Dysfunction Laboratory. SUBJECTS: Twenty-two college women students were studied. They had not been lifting weights or otherwise participating in regular arm exercise for the 6 months before the study. They had no history of upper extremity injury or cardiovascular disease. INTERVENTIONS: Subjects performed one bout of eccentric exercise at a high load to induce elbow flexor muscle injury. Uniform IPC was applied on the day of exercise and daily for 5 days at 60mmHg, 40 seconds inflation, 20 deflation for 20 minutes. MAIN OUTCOME MEASURES: Measurements of arm circumference, stiffness, and isometric strength were recorded before exercise, then before and after IPC for 5 days after exercise. Passive muscle stiffness was measured on a device that extends the elbow stepwise and records the torque required to hold the forearm at each elbow angle. RESULTS: Circumference and stiffness increased and strength decreased during the 5 days post-exercise (p < .05). IPC significantly decreased circumference and stiffness most notably on days 2 and 3 after exercise (p < .05). The strength loss was not affected by IPC. CONCLUSION: IPC is effective in temporarily decreasing the swelling and stiffness after exercise-induced muscle injury.

Adult↗

Compression therapy for treating stage I and II (Widmer) post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep vein thrombosis characterised by chronic complaints, swelling, and skin changes in the affected limb. One in every three patients with deep vein thrombosis develops post-thrombotic complications within five years. OBJECTIVES: To assess the effectiveness of compression therapy in patients with stage I and II post-thrombotic syndrome according to the classification of Widmer. Interventions of interest included elastic compression stockings and mechanical devices, compared with no intervention and with each other. SEARCH STRATEGY: The reviewers searched the Cochrane Peripheral Vascular Diseases Specialised Trials Register (last searched April 2003), and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 1, 2003). In addition, journals, conference proceedings and bibliographies were hand searched. Personal contact with other investigators involved in the clinical area was sought to get information about missed or unpublished studies. SELECTION CRITERIA: Trials that evaluated compression therapy for stage I and II (Widmer) post-thrombotic syndrome. Primary outcomes were leg ulceration, or deterioration of post-thrombotic syndrome. There were no restrictions on date or language. One reviewer (DNK) assessed titles and abstracts for relevance. This was verified independently by a second reviewer (MWCS). DATA COLLECTION AND ANALYSIS: Details of eligible studies were extracted and summarised using data extraction sheets. Data extraction was undertaken by one reviewer (DNK) and verified by a second reviewer (MHP). MAIN RESULTS: Only two trials were identified that addressed physical treatment of post-thrombotic syndrome. Both trials were initiated by the same group of investigators. A cross-over study lasting two months compared low and high pressure with intermittent compression units for severe post-thrombotic syndrome. This showed a beneficial effect of higher pressures. The second study, in patients with mild to moderate post-thrombotic symptoms, showed no effect of elastic compression stockings (30-40 mm Hg at the ankle region) when compared to 'placebo' stockings that were one to two sizes too large. REVIEWER'S CONCLUSIONS: There is some evidence of a beneficial effect of intermittent pneumatic compression units, but the study was too small and of too short a duration to draw strong conclusions. Further research is needed in order to assess whether intermittent pneumatic compression units give long term reduction and relief of the symptoms caused by post-thrombotic syndrome, and prevent deterioration and leg ulceration. The use of elastic compression stockings to treat post-thrombotic syndrome cannot be supported on the basis of the currently available data.

Bandages↗

Prevention of venous thromboembolism.

Of the various prophylactic agents evaluated, four have been found to be effective. These are oral anticoagulants, low-dose heparin, mechanical devices which increase venous blood-flow in the leg, and Dextran. Oral anticoagulants have been shown to be effective in patients having abdominal, thoracic, or hip surgery, when treatment was started either before surgery or in the immediate postoperative period. They have also been shown to be effective in medical patients. The evidence derives from studies which showed that treatment can reduce total mortality, prevents venous thromboembolism detected clinically or at autopsy, and prevents thrombosis diagnosed with venography. On the other hand, the incidence of thrombosis diagnosed by 125I-fibrinogen scanning was not reduced when oral anticoagulants were started just before or just after surgery. This suggests that oral anticoagulant treatment starting in the immediate postoperative period may not prevent formation of the initial thrombotic nidus, but is clinically effective because it prevents extension of the nidus to form a significant thrombus. Bleeding has been a significant complication in almost all studies of surgical patients, and this is the major factor which has prevented widespread use of oral anticoagulant prophylaxis. In addition, the need for careful laboratory monitoring makes this approach inconvenient and adds to its expense. Low-dose heparin has been shown to be effective in general surgical and medical patients, but results have been inconclusive in patients having elective hip surgery, and this approach is probably ineffective in patients with hip fracture. In general surgical patients, low-dose heparin prophylaxis has been shown to prevent pulmonary embolism diagnosed at autopsy examination or with lung scanning, and calf and thigh vein thrombosis diagnosed with 125I-fibrinogen leg-scanning. A slight, but statistically significant, increase in the frequency of wound hematoma and a greater postoperative hematocrit fall have been reported when heparin was given three times daily, but not with the twice daily heparin injection regimen. In these studies, low-dose heparin was given without laboratory control of its anticoagulant effect, so that this prophylactic approach is simple, but the need for subcutaneous injections is a disadvantage of this approach. Results with methods which increase venous blood-flow in the leg have varied, depending on the technic used. Active measures, such as intermittent pneumatic calf compression or peroperative electrical calf muscle stimulation, have been shown to prevent thrombosis detected with 125I-fibrinogen leg-scanning. However, while the evidence suggests that both methods are effective in relatively low risk patients, they may have limited value in the high risk patient who is confined to bed for a long time. These methods are free of side effects and relatively inexpensive, but intermittent calf compression, in particular, is slightly cumbersome...

Abdomen↗