Euglobulin Clot Lysis Time Research Articles

The effect of nitric oxide synthase inhibition on the plasma fibrinolytic system in septic shock in rats.

1. We have investigated the effect of pretreatment of rats with nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) on the E. coli lipopolysaccharide (LPS)-induced changes in the plasma fibrinolytic system, platelet count, fibrinogen level, as well as in gross and microscopic pathophysiological changes indicative of disseminated intravascular coagulation (DIC) in rats. 2. E. coli LPS (6 mg kg-1, i.p.) produced a decrease in the levels of plasma fibrinogen and a drop in the blood platelet count 6 h after administration. The decrease in fibrinogen but not the drop in platelet count was reversed by pretreatment with L-NAME (30 mg kg-1, i.p., 24 h and 15 min before administration of LPS). 3. Pretreatment with L-NAME antagonized the LPS-induced activation of fibrinolysis as measured by changes in the euglobulin clot lysis time (ECLT) and enhanced the LPS-induced rise in the plasma level of plasminogen activator inhibitor (PAI). In animals pretreated with L-NAME there was also a marked reduction in the histological changes indicative of DIC. 4. We propose that L-NAME can act as a protective agent in LPS-induced DIC, and this protection is due to an increased generation of PAI following inhibition of NO synthase.

Heterogeneous mechanisms responsible for reduced fibrinolytic capacity in patients with a history of venous thrombosis

Abnormal response to venous stasis is a frequent finding in patients with previous venous thrombosis. The factors studied to explain the response of the fibrinolytic system to venous occlusion (VO) have included tissue plasminogen activator (t-PA), PAI antigen and activity measurements as additional tests to the conventional euglobulin fibrinolytic activity. However, there is no consensus on the definition of an abnormal response. In order to further investigate the clinical relevance and the definition of good and bad responders (GR, BR), we have used a 10 min VO test in 109 patients with well documented venous thromboembolic events. Hematocrit, euglobulin clot lysis time (ECLT), diluted whole blood lysis time (DWBLT), tissue plasminogen activator (t-PA ag), fibrinolytic activity of euglobulins on fibrin plates (EFA), activity of the t-PA inhibitor (PAI act), a complete study of haemostasis, and a platelet count were performed before and after VO. Clinical characteristics did not reveal a significant difference between GR and BR. Among these 109 patients, 46 patients had a GR according to our previous definition (residual PAI≤2 U/ml). In this subgroup, results are homogeneous in the various fibrinolytic tests used. In the 63 remaining patients, results are heterogeneous: in 28 patients a BR was observed whatever the test used and could be attributed to a high basal PAI act in 17 cases, or a poor t-PA release in 11 cases. In the remaining 35 cases, interpretation of results is difficult: in 16 patients the anomaly of the t-PA-PAI balance coexists with a satisfactory response of global fibrinolytic activity judged on the ECLT after VO (≤90 min) or on the EFA after VO (t-PA>2 U/l). This discordance may be linked to a compensating activity of another pathway of the fibrinolytic system. In 19 cases the discordances remain unexplained. In these subgroups of BR, clinical characteristics were not clearly different. However, the subgroup ‘concordant BR’ seems to be more frequently associated with recurrences or familial thrombotic tendency. This work underlines the difficulties of clinical interpretation of hypofibrinolysis testing. Global tests (ECLT, DWBLT) and EFA are not only dependent on the t-PA-PAI balance but also on the contact phase and u-PA course. Combinations of tests and a better understanding of the multiple pathways involved will be necessary if we wish to prospectively identify patients at significant risk of thrombosis.

The Effect of Erythropoietin on Platelet Function and Fibrinolysis in Chronic Renal Failure

The influence of erythropoietin therapy on platelet function and fibrinolysis was evaluated in 12 anemic hemodialysis patients. Six months of therapy with human erythropoietin (50 to 80 IU/kg initially) raised the hemoglobin level to 10.8 g/dl but did not increase platelet activity in vivo as measured by beta-thromboglobulin or platelet factor 4. There was no change in the platelet aggregation thresholds in vitro for ADP, adrenaline, thrombin or collagen during treatment. Platelet number and volume were also unaffected. Fibrinolytic activity intensified as erythropoietin treatment proceeded, with a fall of euglobulin clot lysis time and rise in the activity of t-PA. PAI-1 levels also showed a downward trend, without reaching significance. Thus erythropoietin treatment in modest doses does not seem to adversely influence the hemostatic system in patients on hemodialysis.

Effect of supine exercise on platelet aggregation and fibrinolytic activity.

In 12 healthy young men, strenuous cycling exercise in the supine position, caused platelet aggregability to decrease and the ADP threshold to rise from 7.0 microM resting, to 9.5 exercising (P < 0.01). At the same time, fibrinolytic activity increased markedly: euglobulin clot lysis time shortened from 178 to 68 min, PAI-1 fell from 8.91 to 5.16 IU ml-1, and t-PA rose from 0.56 to 3.95 IU ml-1, all three values were significant to P < 0.01. When the erect posture was assumed after lying at ease for 1 h after exercise, it did not increase platelet activity as expected, but caused a modest increase of fibrinolytic activity. These results suggest that supine exercise will not affect the haemostatic system adversely.

The Significant Enhancement of Fibrinolysis by Calcium Ion in a Cell Free System: The Shortening of Euglobulin Clot Lysis Time by Calcium Ion

We investigated the roles of calcium ion (Ca2+) on euglobulin clot lysis time (ECLT) and found that the physiological concentration of Ca2+ significantly (4-5 times) shortened ECLT. The shortening was observed at the concentration of Ca2+ higher than 1.5-2.0 mM. Other divalent cations such as Mg2+, Zn2+ or Mn2+ didn't change ECLT. Anti-tPA antibody or plasminogen activator inhibitor-1 prolonged ECLT in the absence of Ca2+, whereas they had no effect on ECLT shortened by Ca2+. C1 inactivator also had no effect. When barium absorbed plasma was employed, the shortening of ECLT by Ca2+ wasn't observed, whereas it was recovered by the readdition of barium absorbed fraction. When factor X deficient plasma was employed, the shortening of ECLT by Ca2+ was also not observed. Thus, Ca2+ enhances fibrinolysis in a cell free system by a novel pathway in which the presence of factor X is prerequisite.

Relationships between serum lipids, serotonin, platelet aggregation and some fibrinolytic parameters in humans

We have studied relationships between serum lipids, plasma serotonin (5-hydroxytryptamine, 5-HT), platelet aggregation in the platelet-rich plasma (PRP), and some fibrinolytic parameters in healthy volunteers. LDL was positively related to 5-HT-induced platelet aggregation. Higher serum HDL levels were related to higher fibrinolytic activity expressed by shorter euglobulin clot lysis time (ECLT). No correlation existed between serum lipids and plasma 5-HT. Plasma 5-HT was found to be related to tissue plasminogen activator (t-PA), suggesting some link between plasma serotonin and the release of t-PA from endothelial cells. There were mutual relations among fibrinolytic parameters such as tissue plasminogen activator (t-PA) antigens, total plasminogen activator inhibitor-1 (PAI-1), t-PA-PAI-1 complex, free PAI-1, and ECLT. In conclusion higher LDL may be more thrombogenic due to enhanced 5-HT induced platelet aggregation whereas high HDL may be more protective against thrombosis due to enhancement of fibrinolysis.

D-dieter during intra-arterial low-dose streptokinase treatment of peripheral arterial occlusive disease

In order to assess systemic and local intra-arterial levels of D-dieter, a specific degradation product of cross-linked fibrin, blood samples were obtained before and 0.5, 1.5, 4, 8, 24, and 48 hours after the start of intra-arterial low dose streptokinase treatment (3750 IU/h) in 21 patients with angiographically documented peripheral arterial occlusive disease. Blood was sampled simultaneously from the cubital vein and from the arterial catheter located close to the occlusive thrombus. Pre-treatment D-dieter levels in arterial and venous blood were 298 and 259 ng/mL (medians), respectively. During the first day of treatment D-dieter levels in arterial blood increased on average 10–20 fold and were at all times significantly higher than D-dieter levels in venous blood (artery vs vein; 0.5 h: 414 vs 266; 1.5 h: 2640 vs 411; 4 h: 2490 vs 898; 8 h: 2640 vs 906; 24 h: 6290 vs 1060 ng/mL, medians). In 13 patients in whom recanalization was achieved D-dieter levels were higher than in 8 unsuccessfully treated patients (vein: p < 0.05; artery: not significant). Significant decreases in plasminogen, α 2-antiplasmin, fibrinogen and euglobulin clot lysis time indicated fibrinolytic activation in local arterial as well as in systemic venous blood. It was concluded that higher D-dieter in the vicinity of the thrombus compared to systemic levels reflected local lysis of fibrin. Systemic levels of D-dieter might provide early information on the efficacy of the treatment.

PADMA-28, a botanical compound, decreases the oxidative burst response of monocytes and improves fibrinolysis in patients with stable intermittent claudication

Thirty-six patients with a median age of sixty-seven years and a median duration of stable intermittent claudication of five years were randomized to either active treatment with PADMA-28 or placebo for four months. The group randomized to active therapy received twice daily two tablets, each tablet containing 340 mg of a dried herbal mixture composed according to an ancient lamaistic preparation. The group randomized to placebo received inactive tablets of indistinguishable taste, colour and size. Platelet aggregation in vitro by ADP or collagen was not significantly changed by PADMA-28, but three statistically significant findings during active drug treatment were: the “oxidative burst” of monocytes, as measured by chemiluminescence, decreased from 75.6 mVolt to 53.5 mVolt; euglobulin clot lysis time was shortened by approximately 40%, signifying a sharp increase in fibrinolytic activity, and PAT-1 activity decreased from 14.6 to 10.1 IU/ml (p < 0.05). Patients on placebo showed no significant changes in any of these parameters. The possible relevance of these biochemical changes to the clinical benefit obtained from PADMA-28 therapy is discussed.

Stress-dependent changes in fibrinolysis, serotonin and platelet aggregation in rats

The effects of different kinds of acute stress on collagen-induced whole blood platelet aggregation and fibrinolysis in relation to blood serotonergic measures were studied. In rats water-immersion restraint stress resulted in a shortening of euglobulin clot lysis time (ECLT), an increase in tissue plasminogen activator(tPA) activity with a concurrent fall in its inhibitor activity. Footshock caused rather a suppression in fibrinolysis with a prolongation of ECLT and a decline in tPA activity as well as a reduction in whole blood platelet aggregation induced by collagen. Serotonin (5-HT) level, a marker of a severity of stress, increased after footshock application with a concomitant rise in its major metabolite-5-hydroxyindoleacetic acid (5-HIAA). This indicates an enhanced 5-HT metabolism. Following water-immersion restraint stress 5-HT and 5-HIAA levels did not differ from controls. In both groups of stressed animals an inverse correlation between tPA activity and blood serotonin was observed. Our data indicate that these types of stress may influence either fibrinolysis or peripheral serotonergic mechanism in different ways. Acute and severe stress such as footshock by causing an impairment in fibriinolysis and a rise in 5-HT may contribute to the pathogenesis of thrombosis and henceforth to the development of atherosclerosis.

Fibrin-specific lysis of microthrombosis in endotoxemic rats by saruplase

The dissolution by the fibrinolytic agent saruplase of microthrombi due to disseminated intravascular coagulation (DIC) has been studied in anesthetized rats. The intravenous infusion of E. coli lipopolysaccharide (endotoxin) for 4 hours (total dose: 25 mg/kg) induced marked thrombocytopenia and hypofibrinogenemia. DIC-related microthrombosis, detected as increased deposition of 125I-labelled human fibrin, was found in the liver and the kidneys, but not in the lungs, the heart, the mesenterium, the spleen and the M. rectus abdominis of endotoxemic rats. Treatment with 1 – 20 μg/kg·min saruplase, that was infused concomitantly with endotoxin, dose-dependently and significantly reduced endotoxin-induced microthrombosis in the liver and the kidneys by 85 resp. 88 %. When saruplase (20 μg/kg·min) was administered only during the last two hours of endotoxin infusion, liver microthrombosis was still significantly dissolved by 69 %, whereas renal microthrombosis was insignificantly reduced by 34 %. The inhibition of endotoxin-induced microthrombosis took place in the same dosage range as the shortening of the euglobulin clot lysis time in normal rats by saruplase as a measure of its fibrinolytic activity. Saruplase did not modify thrombocytopenia and hypofibrinogenemia in endotoxemic rats. Saruplase per se did not affect plasma fibrinogen levels. Thus, in a fibrin-selective dose range saruplase is able to dissolve microthrombosis associated with DIC in endotoxemic rats.

Changes in fibrinolytic parameters in male patients with type 2 (non-insulin-dependent) diabetes mellitus

We examined changes in fibrinolytic parameters in male patients with diabetes mellitus (DM) and controls. DM patients were divided into three groups: patients without retinopathy, patients with simple retinopathy, and patients with proliferative retinopathy. Plasma levels of t-PA (tissue plasminogen activator) and t-PA-PAI-1 (plasminogen activator inhibitor-1) complex increased with increase in age, but those of PAI-1 (total and free) did not change in controls. On the other hand plasma levels of PAI-1 decreased with increase in age in DM patients. Plasma levels of t-PA, t-PA-PAI-1 complex, free and total PAI-1 increased with increase in body mass index in controls, but no significant changes were shown in these parameters in DM patients. When compared with controls, plasma levels of t-PA, t-PA-PAI-1 complex and PAI-1 were lower in DM patients. Plasma levels of UK (urokinase) and Lp(a) were higher in DM patients. ELT (euglobulin clot lysis time) was significantly shorter in DM patients than in controls. Patients without retinopathy showed increased fibrinolytic activities compared with those with retinopathy due to the increased levels of t-PA in plasma. These results seem to indicate that blood vessels release larger amounts of t-PA at the early stage of DM, then release being impaired at its advance stage. It is also suggested that the regulatory control mechanisms of fibrinolytic activity associated with change in age and body mass index are different between patients with DM and normal people.

Fibrinolysis in Pseudotumor Cerebri

Pseudotumor cerebri is a syndrome associated with diverse putative etiological factors that include chemicals such as vitamin A, tetracycline and estrogens or venous circulatory disturbances like sagittal or transverse sinus thrombosis. Diseases predisposing to thrombosis, such as polycythemia vera and essential thrombocythemia, were reported to cause sinus thrombosis and pseudotumor cerebri. This is a pilot study to investigate the possible role of hemostatic factors in the pathogenesis of pseudotumor cerebri. We studied nine patients with severe, recurrent, or refractory pseudotumor cerebri causing visual impairment and found abnormal euglobulin clot lysis time (prestress in all of them and post stress in seven). Digital subtraction angiography was suggestive of recanalized sinus thrombosis in only three patients. We conclude that abnormalities in the fibrinolytic system are present in a subset of patients with severe pseudotumor cerebri, which calls for further studies on venous circulatory pathogenesis of pseudotumor cerebri and the possible role of anticoagulants in such cases.

Effect of a dietary copper deficiency on plasma fibrinolytic activity in male and female mice

To investigate the effects of a dietary Cu deficiency on plasma fibrinolytic activity, groups (n=16) of adult male and female Swiss-Webster mice were fed Cu-supplemented (8.4 mg Cu/kg) or Cu-deficient (0.3 mg Cu/kg) diets ad libitum with deionized water for 43–49 days. Animals were exsanguinated under pentobarbital anaesthesia; platelet-poor plasma was prepared and assayed for euglobulin clot lysis time (ECLT). Plasma protein C (PC) and antithrombin III (AT-III) activities also were determined. No statistically significant effect of Cu deficiency on either PC or AT-III activity was observed but a highly significant (P<0.001) ECLT prolongation in both male and female deficient mice clearly demonstrated that the physiological clot-lysing mechanism must be impaired in these animals. These results may help to explain the thrombotic sequelae of a dietary Cu deficiency in mice.

Impaired fibrinolytic activity induced by ingestion of butter : Effect of increased plasma lipids on the fibrinolytic activity

To investigate the effects of the increased plasma lipid level on fibrinolysis, we measured the levels of fibrinolytic components in serially obtained plasma samples from healthy volunteers after the intake of different amounts of butter. Plasma triglyceride level increased significantly after butter intake compared to the control group. Eight hours after the intake of 100g of butter, plasminogen activator inhibitor 1 (PAI-1) level in plasma was significantly higher and euglobulin clot lysis time was significantly prolonged compared to those of the control group. There was no effect on plasma tissue plasminogen activator level. These results suggest that the temporary increase in plasma triglyceride level induced high PAI-1 level, resulting in impaired fibrinolytic activity. The effect of temporary hyperlipidemia on platelet function was also analyzed and revealed that the response of platelets to ADP and collagen was lower in the butter intake group compared to those of the control.

Conformational change of plasminogen: Effects of N-Terminal peptides of Glu-plasminogen

Seven peptides were synthesized to analyze the mechanism of the intramolecular binding of the N-terminal peptide of Glu-plasminogen (Glu-plg) to its kringles. They were Ala 44-Lys 50, Ala 44-Glu 51, Ala 44-Ser 49, Val 17-Gly 23, Lys 19-Gly 23, Lys 19-Gln 21 and Lys 19-Lys 20. Ala 44-Lys 50, Ala 44-Glu 51 and Lys 19-Lys 20.enhanced the activation of Glu-plg by tissue plasminogen activator (t-PA) or urinary plasminogen activator (u-PA). The activation of Lys-plg, however, was not influenced by these peptides. Therefore, it is suggested that these three peptides worked on Glu-plg in a similar manner as lysine analogue by making the conformation of Glu-plg looser. These peptides did not have any direct effects on u-PA and t-PA. Concerning the effect on fibrinolysis Ala 44-Lys 50 and Lys 19-Lys 20 prolonged euglobulin clot lysis time. These results indicate that Ala 44-Glu 51 may be a responsible binding site in the N-terminal portion of Glu-plg, and LBS of kringle 1 or 4 is the binding site of N-terminal portion of Glu-plg.

Fibrinolytic and Hemorheologic Alterations During and After Elective Aortic Graft Surgery

The hemorheologic and fibrinolytic variables of 15 patients undergoing elective aortic graft surgery were investigated before, during, and after surgery. During the operation, a relative hemodilution was induced intentionally by an infusion of crystalloids and albumin. This led to a decrease in hematocrit (35.5 +/- 6.3-->31.8 +/- 5.6%, P < 0.01), fibrinogen, and platelets, as well as a decrease in fibrinolysis (Euglobulin Clot Lysis Time increases 246 +/- 52-->300 +/- 46 min and fast-acting plasminogen activator inhibitor 1 [PAI-1] activity increases 10.5 +/- 6.9-->15.1 +/- 9 IU/mL, P < 0.01). There was also specific rheologic impairment with a dissociation of erythro-aggregates (primary aggregation time 3.37 +/- 2.63-->7.18 +/- 7.2 s). Tissue-type plasminogen activator (t-PA) antigen was only increased just after surgery (8.3-->14.5 ng/mL, P < 0.01). During the first postoperative week, the acute-phase response subsided. This was accompanied by an increase in fibrinogen, von Willebrand factor antigen, and plasma viscosity (1.33 +/- 0.13-->1.49 +/- 0.13 mPa x s, P < 0.01). Hematocrit and the extrinsic fibrinolytic system (t-PA/PAI) returned to baseline values, whereas intrinsic fibrinolysis remained altered (the Euglobulin Clot Lysis Time, reflecting total activity of plasminogen activators, was still increased). Postoperative management may benefit from a recognition of these two distinct phases induced by surgery. The acute-phase reaction of the first postoperative week is an added vascular risk factor and requires a specific therapeutic approach.

Hemostatic changes in heart transplant recipients and their relationship to accelerated coronary sclerosis.

Hemostasis was assessed in 115 steady-state heart transplant recipients (HTRs) and compared with that of 23 age-matched healthy controls and 21 age-matched patients with ischemic heart disease (IHD). Compared with the controls, the HTRs had increased levels of fibrinogen (mean and 95% confidence limits of 4.50 [4.32-4.68] g/L versus 3.47 [3.07-3.87] g/L, P < 0.001), factor VIIC (1.16 [0.98-1.21] IU/ml versus 0.99 [0.89-1.10] IU/ml, P < 0.001), and von Willebrand factor antigen (1.72 [1.58-1.88] IU/ml versus 1.00 [0.80-1.26] IU/ml, P < 0.001). HTRs had increased antithrombin III activity (P = 0.002) and protein C activity (P = 0.002), with a decrease in total protein S levels (P < 0.001) but no change in free protein S levels. Stepwise discriminant analysis of hemostatic variables showed that fibrinogen was the best discriminator of the three groups, classifying 55.6% of HTR, 40% of IHD, and 66.7% of the controls. More marked prothrombotic changes were found in HTRs transplanted for IHD than for other causes; this reached significance for prothrombin (P = 0.048), factor IX (P = 0.003), and poor fibrinolytic activity as measured by euglobulin clot lysis time (P = 0.008). The HTRs with accelerated coronary sclerosis (ACS) tended to have the most prothrombotic changes; this reached significance with factor IX (P = 0.03). In conclusion, HTRs have perturbed hemostasis; the net effects of these changes are prothrombotic. The relationship between prothrombotic changes and ACS merits further studies.

Biological risk factors for restenosis after percutaneous transluminal coronary angioplasty

In an attempt to discern biological (such as thrombotic or fibrinolytic) risk factors in patients developing restenosis after percutaneous transluminal coronary angioplasty, the following factors were measured prior to angiography in a population of 23 patients (20 men, 3 women, mean age 57 ± 5 yr) treated by a successful angioplasty (gain > 20% and residual stenosis < 50%) for stable angina pectoris and who had a routine angiographic restudy. The following factors were thus assessed: lipid factors: cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein AI, apolipoprotein B; coagulation factors: fibrinogen, antithrombin III, fibrinopeptide A, factor VIII coagulant, factor VIII antigen, protein C; factors of physiological fibrinolysis: plasminogen, α2-antiplasmin, tissue plasminogen activator and euglobulin clot lysis time before and after venous occlusion, plasminogen activator inhibitor before venous occlusion; and factors of platelet release: β-thromboglobulin, platelet factor 4. Also studied were clinical characteristics: age, gender, diabetes, hypertension, smoking habits, previous myocardial infarction; angiographic data: global extent of coronary artery disease, location of the stenosis in a bend or branch point, complexity of the lesion, initial and residual stenosis and treatment during follow-up. The coronary angiograms were analyzed by a computer-assisted method with automatic edge detection. On angiographic criteria, 6 patients (restenosis group) were judged to have developed a restenosis (30% decrease in diameter and/or return to a 50% stenosis). The other 17 patients (those without restenosis) were considered to have a persistent success. Apart from age (group without restenosis: 55 ± 6; restenosis group 61 ± 5, p < 0.04), there were no differences in clinical, angiographic or treatment variables. There were no differences in lipid factors, but significant differences were observed in hemostatic variables: fibrinogen (without restenosis: 3.18 ± 0.83; restenosis: 3.83 ± 0.51 g/l, p = 0.05), tissue plasminogen activator before venous occlusion (without restenosis: 10.9 ± 26.8; restenosis: 232.5 ± 371.2 IU, p < 0.04), euglobulin clot lysis time after venous occlusion (without restenosis: 176.5 ± 100.5; restenosis: 78.6 ± 40.2 min, p < 0.05) and for marker of the platelet release: platelet factor 4 (without restenosis: 10.8 ± 7.9; restenosis: 20.5 ± 7.5 ng/l, p < 0.04). These findings indicate that patients developing restenosis after coronary angioplasty tend to have an imbalance in the prothrombotic-antithrombotic equilibrium prior to the procedure.

Fibrinolytic response to venous occlusion in healthy subjects: Relationship to age, gender, body weight, blood lipids and insulin

The physiological variability of fibrinolytic response to 20 min upper arm venous occlusion was studied in 191 healthy women and men, 19–80 years old. It was observed that fibrinolytic response measured by the absolute amount of t-PA antigen after venous occlusion increased with increasing age (from 10.7 at 19–30 years to 25.0 ng/ml at 71–80 years), was higher in men than in women (20.9 vs 15.6 ng/ml), higher in obese than in slim subjects (29.5 vs 12.3 ng/ml) and higher in subjects with moderately elevated blood cholesterol (33.3 vs 18.2 ng/ml) and triglycerides (30.0 vs 24.4 ng/ml, all p<0.05 or less) than in subjects with normal levels of these variables. Due to simultaneous increase in basal levels of t-PA antigen in all these cases, relative increases in t-PA antigen after venous occlusion were not altered. Fibrinolytic response measured by t-PA activity, but not with euglobulin clot lysis time, increased with age. PAI-1 antigen was not affected by venous occlusion, while PAI activity decreased to zero in most subjects (in 61–80%) regardless of age, gender or blood lipids. However, in obese subjects and especially in subjects with elevated insulin, fibrinolytic response was reduced as determined by residual PAI activity after venous occlusion (1.3 and 10.6 IU/ml, respectively) due to the increased basal level of PAI-1. It was concluded that age, gender, body weight, blood lipids and insulin significantly modulate fibrinolytic response to venous occlusion.

Beneficial Effects of Intermittent Suction and Pressure Treatment in Intermittent Claudication

The present study reports on the effects of a physical treatment modality in patients with intermittent claudication. During this treatment a major part of the skin surface is subjected to intermittent suction and pressure. In a previous, preliminary study the authors found a beneficial effect of this treatment in intermittent claudication. The study included 34 patients with moderate, stable intermittent claudication. Twenty-two patients participated in a double-blinded, randomized trial comparing the effects of 25 treatments to 25 placebo applications given over a period of two months. Twelve patients participated in an open trial investigating the possible effects of the treatment on platelet aggregation and fibrinolysis. Pain-free and maximal walking distances were measured on a treadmill, and systolic blood pressure was measured on the upper limb, the ankle, and the first toe bilaterally. The threshold for adenosine diphosphate (ADP)-induced platelet aggregation was tested, and the fibrinolytic activity was estimated from the euglobulin clot lysis time. Active treatment resulted in significant improvements in pain-free and maximal walking distances, whereas no changes could be found during placebo administration. The treatment caused significant increments in the ADP thresholds for platelet aggregation, while the effects on fibrinolysis were uncertain. It is concluded that intermittent suction and pressure treatment offers a new approach for conservative treatment of intermittent claudication.