The effect of external pneumatic compression on regional fibrinolysis in a prospective randomized trial

INTRODUCTION: External pneumatic compression devices (EPC) prevent deep venous thrombosis (DVT) by reducing lower extremity venous stasis. Early studies suggested they also enhance fibrinolytic activity; however, in a recent study, EPC had no effect on systemic fibrinolysis in patients undergoing abdominal surgery. The hypothesis of this study was that EPCs enhance regional fibrinolysis in these subjects. METHODS: Forty-five patients (44 male, one female; mean age, 67 years) undergoing major abdominal surgery (35 bowel procedures, 10 aortic reconstructions) were prospectively randomized to one of three groups for DVT prophylaxis: subcutaneous heparin injections (HEP), thigh-length sequential EPC devices (EPC), or both (HEP+EPC). Prophylaxis was begun immediately before surgical incision and continued until postoperative day 5 or patient discharge. Venous blood samples were collected from the common femoral vein for measurement of regional fibrinolysis after induction of anesthesia but before initiation of prophylaxis, and on postoperative days 1, 3, and 5. A baseline sample was collected the day before surgery. Fibrinolysis was quantified with measurement of the activities of tissue plasminogen activator (tPA; the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1) with amidolytic technique. RESULTS: tPA activity in all groups was normal at baseline; baseline PAI-1 activity was elevated. Within each prophylaxis group, no significant changes occurred in either tPA or PAI-1 activities after induction of anesthesia or after surgery compared with before surgery (P >.05, analysis of variance with repeated measures). No changes occurred between postoperative samples and after anesthesia within each group. No significant enhancement of fibrinolysis, manifested as either increased tPA activity or decreased PAI-1 activity, occurred in either EPC group compared with the HEP group at any time point (P >.05, analysis of variance with repeated measures). No differences were noted when surgery was performed for malignant disease versus nonmalignant disease. CONCLUSION: In this study, enhanced regional fibrinolysis in the lower extremities could not be detected with the use of EPCs, as measured with tPA and PAI-1 activity in common femoral venous blood samples. EPC devices do not appear to prevent DVT with fibrinolytic enhancement; effective and safe prophylaxis is provided only when the devices are used in a manner that reduces lower extremity venous stasis.     

External pneumatic compression does not increase urokinase plasminogen activator after abdominal surgery

External pneumatic compression (EPC) devices prevent lower extremity deep venous thrombosis (DVT) by reducing stasis. There is a widely held belief that they also enhance endogenous fibrinolysis; however, recent studies of tissue plasminogen activator (the primary activator of fibrinolysis) and plasminogen activator inhibitor-1 (the primary inhibitor of fibrinolysis) failed to confirm this. The hypothesis of this study was that EPC devices increase the level of urokinase plasminogen activator (uPA), a second activator of fibrinolysis. This was a prospective trial in which 44 subjects who underwent major abdominal surgery were randomized to receive unfractionated heparin injections, thigh-length sequential EPC devices, or both for DVT prophylaxis. Prophylaxis was begun immediately before surgical incision and continued until postoperative day 5 or discharge. Venous blood samples were collected from an antecubital vein for measurement of systemic uPA levels and from the common femoral vein for measurement of regional uPA levels. Samples were collected the day before surgery, after induction of anesthesia but before surgical incision, and on postoperative days 1, 3, and 5. uPA levels (ng/mL) were measured with an enzyme-linked immunoassay. Baseline uPA levels (0.41 to 0.56 ng/mL; P >.05, analysis of variance with repeated measures) were similar among the three groups. uPA levels did not change after surgery in systemic or regional blood samples in any group. There were no significant differences in systemic or regional uPA levels in the groups treated with EPC devices relative to those treated with heparin at any time point (P >.05, analysis of variance with repeated measures). Enhancement of fibrinolysis with EPC devices remains unproven; the findings reported here suggest that effective DVT prophylaxis can only be assured when the devices are used in a manner that reduces venous stasis.     

Relationship between postsurgical fibrinolytic parameters and deep vein thrombosis in surgical patients treated with compression devices

This study consisted of 52 patients admitted for orthopedic surgery and 28 patients admitted for general surgery, who were treated with Sequential Compression Devices (SCD) and Thromboembolic Deterrent Stockings (TEDS) and monitored for the development of deep vein thrombosis (DVT). Coagulation and fibrinolytic profiles were carried out on these patients preoperatively, and on days one, three, and six postoperatively. All patients were followed by I-125-Fibrinogen scanning, Venous Doppler, and Impedance Plethysmography studies for clot detection. In the orthopedic surgery group, six (11.5%) developed DVT, and in the general surgery group, one (3.6%) developed DVT. No patients developed pulmonary embolism. The combined incidence of DVT was 8.8 per cent. A variety of parameters was measured in order to determine whether compression devices prevent a fibrinolytic shut-down commonly seen in the postsurgical patient. A combination of three assays was found to be significant in demonstrating a fibrinolytic response. These parameters were a post-surgical decrease in the plasminogen level, an increase in the level of free protease activity postoperatively, and an increase in the level of tissue plasminogen activator after surgery. 56.3 per cent of all patients treated with SCD and TEDS showed a fibrinolytic response on postoperative day one by a combination of all three of these parameters. In the group of patients that developed DVT none showed an increase in free protease activity, and five of seven showed no significant decrease in plasminogen and no increase in tissue plasminogen activator. Patients who developed thrombosis had measurable differences in their fibrinolytic system compared to those without postoperative thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of pneumatic compression on fibrinolysis after total hip arthroplasty

The purpose of this prospective randomized clinical study was to investigate the enhanced systemic fibrinolysis mechanism of venous thrombosis prevention by pneumatic compression after total hip arthroplasty. Fifty patients were randomized into one of two groups (one with pneumatic compression [n=25] and one without [n=25]). Blood was drawn from a radial arterial line immediately preoperatively (baseline), at skin closure, and 8 hours and 22 hours after the baseline sample. Serum determinations of antigen of tissue plasminogen activator and plasminogen activator inhibitor-1 were done using enzyme-linked immunosorbent assays. These data do not support the enhancement of systemic fibrinolysis mechanism for lowering thromboembolic risk after total hip arthroplasty by pneumatic compression devices. The results of this study showed no differences that were statistically significant between the two groups. The greatest difference was observed 8 hours after surgery for the plasminogen activator inhibitor-1 marker, (28.12 with compression versus 22.07 ng/mL without); however, this result was not statistically significant. The beneficial effect of mechanical compression is more likely achieved through increased flow, local fibrinolytic effects, or both.     

Effects of omentectomy on the peritoneal fibrinolytic system

PURPOSE: Decreased fibrinolytic activity in the serosal surfaces of peritoneal tissue appears to be a major factor in the development of peritoneal fibrous adhesions. The omentum reduces peritoneal adhesion by creating a mechanical barrier and producing fibrinolytic factors. This experimental study was designed to investigate the effects of omentectomy on the peritoneal fibrinolytic system. METHODS: Thirty animals were assigned randomly to a control group or an omentectomy group. On postoperative day 10, peritoneal and blood samples were collected and adhesions were graded qualitatively. We measured the concentrations of serum and peritoneal tissue plasminogen activator, peritoneal plasminogen activator inhibitor-1, tissue plasminogen activator/plasminogen activator inhibitor complex, and hydroxyproline. RESULTS: Adhesions were significantly increased after omentectomy. Omentectomy also resulted in a reduction of both serum and tissue "tissue plasminogen activator" levels. On the other hand, an increment in "plasminogen activator inhibitor-1" levels was observed after omentectomy. There were no differences in "tissue plasminogen activator/plasminogen activator inhibitor" complex or "hydroxyproline" levels. CONCLUSION: Omentectomy reduced peritoneal fibrinolytic activity significantly and the peritoneal plasminogen activator system showed corruption that did not resolve with the rest of the peritoneal system after omentectomy.     

Plasma fibrinolytic activity in patients undergoing major abdominal surgery

The fibrinolytic system was studied in 30 patients undergoing elective cholecystectomy and in 30 with more advanced elective abdominal surgery. Blood was sampled before, during and after operation for determination in plasma of the tissue plasminogen activator (t-PA), the recently described fast t-PA inhibitor, and plasmin alpha 2-antiplasmin complex (PAP). In addition the t-PA activity during venous occlusion was determined preoperatively. Most of the patients showed raised t-PA levels during surgery, but the interindividual variation was wide and was not correlated to fibrinolytic capacity measured preoperatively as enhancement of t-PA activity during venous occlusion. The levels of the t-PA inhibitor rose during and immediately after surgery, and were higher in patients without increased t-PA activity during surgery. The patients with more advanced disease had higher levels of the inhibitor than the cholecystectomy patients. The data suggest that the t-PA inhibitor may influence the fibrinolytic response to surgical trauma and may explain the previously reported shutdown in fibrinolysis in the early postoperative period. PAP, used as reflecting the overall fibrinolytic activity, was increased in plasma after the first postoperative days.     

Regional hyperthermic fibrinolytic perfusion after unsuccessful venous thrombectomy of extensive deep venous thrombosis

OBJECTIVE: Because of the dose-dependent increase in bleeding complications, the intraoperative administration of fibrinolytic agents is limited. This limitation impairs the efficacy of fibrinolytic therapy because low-dose fibrinolysis often fails in the treatment of complex deep venous thrombosis (DVT). The aim of this study was to investigate the efficacy and safety of intraoperative high-dose fibrinolytic therapy for extended DVT, which was performed with the regional hyperthermic fibrinolytic perfusion (RHFP) technique. METHODS: From January 1993 to June 2001, in 53 patients with extended DVT, unsuccessful venous thrombectomy (recanalization, <50%) was followed by RHFP with 0.5 mg/kg of body weight of recombinant tissue plasminogen activator. The extent of thrombosis was documented before, during (after the surgical thrombectomy), and after (between postoperative days 2 and 5) surgery with phlebography and was quantified with the Marder score. Intraoperative and postoperative complications were recorded prospectively. RESULTS: After RHFP, a recanalization was achieved in 64 of 146 venous segments (43.8%) that were still occluded despite thrombectomy. Eighty-two segments (56.2%) remained occluded. Compared with the preoperative phlebography, 32 patients (60.3%) had a successful recanalization (>50%). Eleven patients (20.8%) showed minimal and 10 patients (18.9%) no recanalization. No lethal complications occurred. One patient (1.9%) had pulmonary embolism develop, and two patients (3.8%) had bleeding complications develop. CONCLUSION: With the intraoperative use of hyperthermia-assisted high-dose fibrinolysis, improvement of the results of mechanical thrombectomy of extended DVT was possible. The RHFP protected against systemic side effects of the fibrinolysis and show a high safety of application.     

Fibrinolysis after application of a pneumatic tourniquet

The fibrinolytic system was studied after application of a pneumatic tourniquet in 22 patients undergoing elective orthopaedic surgery and during 20-min venous occlusion in 17 healthy subjects. Blood was sampled before anaesthesia (A), before operation (B) and after operation from the ipsilateral (C) and the contralateral (D) limb. Tissue plasminogen activator (t-PA) activity, t-PA antigen and t-PA activity/t-PA antigen ratio increased by, respectively, 557, 109 and 168% in the C samples as compared with A blood (all differences statistically significant). The t-PA activity and t-PA antigen increased slightly in the systemic circulation (B and D) but were significantly less in C than after venous occlusion. Fast-acting inhibitor of t-PA increased significantly in C (15%). During compression with a pneumatic tourniquet, mainly local fibrinolytic activation occurs, and this activation partly explains the low incidence of postoperative deep venous thrombosis after use of a tourniquet.     

止血药对腹部手术后凝血功能及深静脉血栓形成的影响

目的探讨止血药对腹部手术后凝血功能及深静脉血栓形成的影响。方法2008年6月至2009年1月间福建医科大学附属协和医院收治的60例胃肠道肿瘤手术患者（胃癌20例,结肠癌40例）,按随机数字表法分为使用与不使用止血药两组,每组30例。止血药组于手术当天、术后第1天应用巴曲亭2U／d。检测手术前、后D-二聚体（D—D）、组织纤溶酶原激活物（t-PA）、组织纤溶酶原激活抑制物（PAI．1）、凝血酶原时间（PT）、部分活化凝血酶时间（APTT）、凝血酶时间（TT）及血小板（PLT）的变化,并于术后5-7d行下肢深静脉彩超检查以明确有无血栓形成。结果与术前相比,两组患者术后D-D、t-PA、PAI-1均明显升高,PT、APTT延长,TT缩短,PLT减少,差异均有统计学意义（P〈0．05,P〈0．01）。与非止血药组相比,止血药组患者术后D．D、t—PA、PAI-1明显增高,TT缩短,差异有统计学意义（P〈0．05,P〈0．01）。止血药组和非止血药组分别有7例（23．3％）和3例（10．0％）术后出现左下肢深静脉血栓形成,差异无统计学意义（P〉0．05）。结论腹部手术后血液呈高凝状态．易导致深静脉血栓形成。术后使用止血药可加重高凝状态,增加深静脉血栓发生率;术后预防性止血药的应用应慎重。     

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.     

Prospective randomized trial to determine the influence of laparoscopic and conventional colorectal resection on intravasal fibrinolytic capacity

Background: Although the pneumoperitoneum decreases venous reflux from the lower extremities, the rate of thromboembolic complcations seems to be lower after laparoscopic than after conventional procedures. Therefore, it has been assumed that laparoscopic surgery better preserves the intravasal fibrinolytic capacity. The aim of this study was to determine the influence of the operative technique on intravasal fibrinolytic capacity in colorectal resection. Methods: Randomized controlled trial conducted in parallel with the multicenter trial LAPKON II comparing the long-term effects of elective laparoscopic (group I) and conventional (group II) resections for colorectal cancer. Blood samples were taken from 30 patients preoperatively, at the beginning and end of surgery as well as 2, 8, and 24 hr postoperatively. Activities and concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA/PAI complex, fibrinogen, and D-dimers were determined in all specimen with ELISA tests. Area under the curve values (AUC) were calculated for all parameters. Results: Patient characteristics and indication for surgery were not different between both groups. Preoperative values of fibrinolytic parameters were similar in both groups. Postoperatively, tPA activity decreased significantly in both groups, but AUC values for tPA and PAI-1 activity (p = 0.23; p = 0.68); concentration of tPA, PAI-1, and tPA/PAI complex (p = 0.52; p = 0.78; p = 0.95); and concentration of fibrinogen and D-dimers (p = 0.67; p = 0.71) did not differ between the groups. Conclusions: An intravasal fibrinolytic "shutdown" occurs not only after conventional but also after laparoscopic colorectal resection. Both operative techniques had similar effects on postoperative intravasal fibrinolytic capacity. Therefore, the lower incidence of thromboembolic complications after laparoscopic colorectal resections does not seem to be caused by a lesser depression of the intravasal fibrinolytic capacity.     

Thrombotic risk factors associated with transurethral prostatectomy.

OBJECTIVE: To ascertain the potential thrombotic risk associated with transurethral prostatectomy (TURP). PATIENTS AND METHODS: The changes in coagulation variables were assessed in a prospective study of 40 patients undergoing TURP. RESULTS: There was a significant increase in thrombin-antithrombin complexes 6 h after TURP (anova, P=0.01) combined with a significant decrease in activated partial thromboplastin time (anova, P=0.006), suggesting a postoperative hypercoagulable state. The significant increase in d-dimer 24 h after TURP (anova, P=0.015) in the absence of any significant rise in tissue plasminogen activator antigen levels perioperatively (anova, P=0.737) suggests a physiological fibrinolytic response to the developing procoagulant state. The absence of any significant increase in plasminogen activator inhibitor-1 antigen perioperatively (anova, P=0.348) suggests the observed hypercoagulability is not due to a 'fibrinolytic shutdown' reported in other forms of surgery. CONCLUSION: TURP is associated with a hypercoagulable prothrombotic state; aspirin withdrawal perioperatively may be hazardous, and low-dose heparin prophylaxis for venous thrombosis should be considered.     

Indicators of depressed fibrinolytic activity in pre-operative prediction of deep venous thrombosis

Euglobulin lysis time (ELT), tissue plasminogen activator (tPA), and the fast-acting inhibitor of tPA, were measured pre-operatively in 128 patients who underwent elective major abdominal surgery. Deep venous thrombosis (DVT) was detected by 125I-labelled fibrinogen scan in 37 patients (29 per cent) after operation. Pre-operatively, there was diminished euglobulin lysis activity (332 +/- 197 versus 255 +/- 156 min, mean +/- s.d.; P less than 0.025), and tissue plasminogen activator activity (4.2 +/- 9.9 versus 7.7 +/- 14.3 milliunits/ml, mean +/- s.d.; P = 0.094) in patients who subsequently developed postoperative DVT compared with those who did not. There was no significant difference between the two groups in the level of inhibition of tissue plasminogen activator (160.6 +/- 75.4 per cent versus 152.5 +/- 77.5 per cent, mean +/- s.d.; n = 47). Stepwise logistic discriminant analysis of the data obtained preoperatively showed that tissue plasminogen activator, a more specific measure of fibrinolytic activity, was a weaker predictor of DVT than euglobulin lysis time. The results confirm other observations which indicate that lowered fibrinolytic activity is a risk factor for postoperative DVT. In addition, they suggest that this is not due entirely to low levels of activity of tissue plasminogen activator in plasma.     

Impaired fibrinolysis in cyclosporine-treated renal transplant patients. Analysis of the defect and beneficial effect of fish-oil.

Cyclosporine treatment has been associated with thrombotic vascular complications. We investigated the activity of the fibrinolytic system and its capacity to respond upon DDAVP stimulation in a group of 20 cyclosporine-treated patients as compared with a group of 9 azathioprine-treated patients. Furthermore, the effect of the administration of fish-oil to these patients on the endogenous fibrinolytic activity was studied in a double-blind randomized, placebo-controlled cross-over study. The cyclosporine-treated patients showed a significantly reduced plasminogen activator activity and plasmin generation response upon the infusion of DDAVP as compared with the azathioprine group. In the cyclosporine group 60% of the patients had an impaired fibrinolytic response, whereas this was found in only 11% of the azathioprine-treated patients (P < 0.05). The impairment of the endogenous fibrinolysis activity could be attributed either to a defective release of plasminogen activator from the vessel wall (67% of patients) or to high plasma levels of plasminogen activator inhibitor 1 (33% of patients). Administration of fish-oil resulted in a significant improvement of the impaired fibrinolysis in the cyclosporine group. Particularly, in patients with a defective release of plasminogen activator from the vessel wall, fish-oil treatment resulted in a normalization of the fibrinolytic activity. These results indicate that cyclosporine treatment induces an impaired fibrinolysis that may contribute to the frequent occurrence of thromboembolic complications and eventually the impairment of renal function in cyclosporine-treated patients. The beneficial effect of the administration of fish-oil on the endogenous fibrinolysis may result in a reduction of the adverse events associated with cyclosporine treatment.     

Decreased fibrinolytic capacity in coronary patients by increased plasminogen activator inhibitor activity]

The fibrinolytic capacity of the blood mainly depends on the amount of tissue-plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI). In this study the fibrinolytic response to a venous occlusion test (VOT) was measured in 109 patients with angiographically documented coronary artery disease (CAD) and in 20 healthy volunteers at comparable age (controls). CAD-patients had higher plasma plasminogen activator inhibitor capacity before (24.4 +/- 11.0 vs. 15.4 +/- 5.2 arbitrary units [AU/ml]; p less than 0.0002) and after VOT (19.6 +/- 13.2 vs. 10.9 +/- 5.3 AU/ml; p less than 0.0001) compared with controls. Furthermore they showed significant lower plasma t-PA activity after VOT (3.0 +/- 6.8 vs. 6.6 +/- 10.6 AU/ml; p less than 0.0001). However there were no difference between both groups in plasma t-PA antigen levels after VOT (17.3 +/- 12.1 vs. 18.7 +/- 14.4 ng/ml). In 10% of patients the decrease in fibrinolytic activity resulted from a lower t-PA release ("lower" was defined as mean minus one standard deviation of the control group). 40% showed elevated plasma PAI capacity before VOT ("elevated" was defined as mean plus two standard deviations of the control group). Both caused significantly reduced post occlusion plasma t-PA activity and prolonged Euglobulin clot lysis time (p less than 0.003). A positive correlation was found between PAI capacity and serum triglyceride levels. Reduced fibrinolytic activity in 109 patients with coronary heart disease based either on a decrease in t-PA antigen release or a increased in PAI capacity in comparison with healthy controls. The mechanism of these findings is not yet well-known.(ABSTRACT TRUNCATED AT 250 WORDS)     

Double-blind randomized trial of perioperative fibrinolytic enhancement for femoropopliteal bypass

Patients with rest pain or acute peripheral arterial thrombosis are known to have impaired endogenous fibrinolysis, which is associated with an increased risk of early vascular graft thrombosis. This risk is exacerbated by the fibrinolytic shutdown which is known to occur after major surgery. Stanozolol, which has been demonstrated to enhance endogenous fibrinolysis, was therefore used in an attempt to prevent this perioperative fibrinolytic shutdown and so enhance graft patency. Twenty-seven patients were randomized to receive either 50 mg stanozolol or placebo intramuscularly 24 h before operation, followed by a 6 week course of either 5 mg stanozolol or placebo orally, twice daily. On the second day after operation, 10-11 MBq of autologous 111indium-labelled platelets were injected, with scanning over the graft on the 3 following days. Despite using a large depot of stanozolol, significant effects, such as raised plasminogen (P less than 0.001), reduced fibrinogen (P less than 0.001) and reduced euglobulin lysis time (P less than 0.001), were not seen until the seventh day after operation, with maximum benefit at 6 weeks. This was reflected in the 111indium-labelled platelet deposition studies. The placebo group had a progressive increase in platelet deposition on all 3 days. In contrast, those receiving stanozolol showed a lower, static picture of deposition. However, these changes did not attain statistical significance. Three patients experienced early graft thrombosis, two in the placebo group and one in the stanozolol group. Only an incomplete inhibition of the perioperative fibrinolytic shutdown was achieved. Much longer preoperative courses are thus required to allow the maximum effect to be present at the most crucial time. At present, perioperative fibrinolytic enhancement does not appear to be a practical proposition, and we must await the development of new safer and more potent agents.     

Factors affecting the fibrinolytic response to surgery.

The stress of injury and surgical operation results in an initial increase in the spontaneous fibrinolytic activity of the blood which is followed by a period of reduced activity in the postinjury or postoperative period. This 'fibrinolytic shutdown' is particularly marked in patients with malignant disease and occurs irrespective of whether or not they develop a deep venous thrombosis. It also occurs in patients with benign disease and in these patients is greater, though only on the first postoperative day, in those who develop deep venous thrombosis. Venous occlusion studies suggest that this reduction in spontaneous fibrinolytic activity may be the results of a reduction in the fibrinolytic capacity of the vascular endothelium resulting either from a deficiency of the enzyme plasminogen activator or an inability to release the enzyme from the endothelium. Changes in antiplasmins, the inhibitors of the fibrinolytic system, also occur as a result of the stress of operation. Plasma levels of alpha2-macroglobulin fall while those of alpha1-antitrypsin rise. These changes occur irrespective of the presence of malignant or benign disease and do not appear to influence the development of deep venous thrombosis.     

Comparison of extradural and general anaesthesia on the fibrinolytic response to total knee arthroplasty

Extradural anaesthesia is associated with lower incidences of deep vein thrombosis after total knee arthroplasty. It is not known if the type of anaesthesia influences thrombogenesis or fibrinolysis during knee surgery performed under tourniquet. We studied 31 patients allocated randomly to receive either extradural or general anaesthesia for primary unilateral total knee arthroplasty performed under tourniquet. Radial artery blood samples were obtained before surgery, during surgery with the tourniquet inflated and on deflation of the tourniquet. Plasma samples were assayed for markers of thrombin generation and fibrinolysis. Two of the circulating indices of thrombin generation, fibrinopeptide A and thrombin-antithrombin complexes, increased to a similar degree in the perioperative period in both groups. Fibrinolytic activity was similar in both groups, as measured by tissue plasminogen activator (t-PA) antigen, t-PA activity, t-PA- plasminogen activator inhibitor complexes, alpha 2-plasmin inhibitor- plasmin complexes and D-dimer. Extradural and general anaesthesia did not result in significant differences in either thrombin generation or fibrinolytic activity during total knee arthroplasty performed under tourniquet.      

Role of thrombotic and fibrinolytic disorders in the etiology of Perthes' disease

The etiologic role of thrombotic and fibrinolytic disorders in Perthes' disease has not been determined. A case control study was conducted to determine whether thrombotic and fibrinolytic disorders are associated with Perthes' disease. Twenty-six patients with Perthes' disease were matched with 26 control patients for gender, age (2-year range), and time of presentation (1-year range). Thrombotic disorders were investigated for protein C activity, protein S activity, antithrombin III, anticardiolipin antibody immunoglobulins G and M, and lupus anticoagulant. Fibrinolytic disorders were investigated for tissue-plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-1 to tissue plasminogen activator ratio, lipoprotein (a), and plasminogen. The activity of protein C, which suppresses factor Va and leads to an increase of coagulant activity when decreased, was increased in patients. There were no significant differences in the levels of other factors between the patients and controls. No evidence was found to prove a relationship between Perthes' disease and thrombotic or fibrinolytic disorders in the patients in the current study.     

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.