Lifestyle, fibrinolysis and lipids.

Lifestyle including eating habits, physical training, smoking, drinking alcoholic beverages etc. can to a certain extent maintain or spoil our health. The physiological mechanisms of haemostasis and of lipoprotein metabolism play a role in acute cardiovascular diseases but also in a great number of chronic diseases in which vascular pathology is prominent. Imparied fibrinolysis and increased lipid levels are often incriminated in vascular disease. Lifestyle can modify fibrinolysis as well as lipid levels. Physical training, moderate eating habits, no smoking, moderate alcohol intake will be a beneficial influence on both fibrinolysis and lipid levels. The possibility that long-term pharmacological intervention may adversely affect fibrinolysis and lipid levels should always be considered.

A specific allele of the histidine-rich glycoprotein (HRG) locus is linked with elevated plasma levels of HRG in a Dutch family with thrombosis.

Recent studies describe families with both elevated plasma HRG levels and thrombosis. In order to study the possibility that allelic variants of the HRG locus are associated with differences in HRG level, we studied linkage between HRG levels and a dinucleotide repeat polymorphism in a Dutch family which was selected on the presence of both thrombosis and elevated plasma HRG levels. No other known risk factors from thrombosis were found in this family. Linkage was calculated between the dinucleotide repeat and the HRG level considering the HRG level as a quantitative phenotype assuming a population prevalence of elevated HRG of 5%. Two classes of HRG levels were defined by a mean and a variance: one class with normal HRG levels and a second class with high HRG levels. Using a mean HRG level of 99% for individuals with a normal HRG level and 145% for individuals with high HRG, a maximum lod score of 4.17 (odds in favour of linkage of 22,000:1) was found at a recombination fraction of 0, indicating linkage. Considering the pedigree, an association was found between the presence of a specific allele (no. 6) of the dinucleotide repeat polymorphism and plasma HRG levels. Family members carrying allele 6 were found to have higher HRG plasma levels compared with family members lacking allele 6 (149% v 109% respectively). We conclude that in this family, linkage is found between the HRG locus and the HRG level, and that a HRG gene coupled to allele 6 of the dinucleotide polymorphism is associated with elevated plasma HRG levels. No evidence was found for a causal relationship between elevated plasma HRG levels and thrombosis in this family.

Effect of low-dose aspirin during pregnancy on fibrinolytic variables before and after parturition.

OBJECTIVE: We assessed the effects of a daily oral dose of 60 to 80 mg of aspirin from 12 weeks' gestation until delivery on fibrinolytic variables before and after parturition. STUDY DESIGN: In a prospective controlled study labor was electively induced in 24 patients, eight receiving low-dose aspirin and 16 controls. Levels were determined in maternal and cord plasma of tissue-type plasminogen activator antigen and activity, plasminogen activator inhibitor-1 antigen, plasminogen activator inhibitor activity, and plasminogen activator inhibitor-2 antigen. We also determined metabolites of vascular prostacyclin and platelet thromboxane A2. RESULTS: The only maternal fibrinolytic variable affected by low-dose aspirin was plasminogen activator inhibitor activity, which showed a significant reduction before and after parturition of 40% and 70%, respectively, in low-dose aspirin users compared with controls. Concentrations of thromboxane B2 in women using low-dose aspirin were 7% (maternal serum) and 17% (cord serum) of values in controls, but concentrations of 6-keto-prostaglandin F1 alpha were not affected. CONCLUSIONS: Low-dose aspirin reduces plasminogen activator inhibitor activity and platelet reactivity, but not prostacyclin synthesis, before and after parturition. The reduction in plasminogen activator inhibitor activity may be caused by inhibition of platelet reactivity.

The fibrinolytic system in the hemolytic uremic syndrome: in vivo and in vitro studies.

Fibrinolytic parameters and von Willebrand factor (vWF) antigen were measured in the plasma of 10 patients with hemolytic uremic syndrome (HUS). Samples were taken at presentation and again 2 wk later, before and after infusion of 1-desamino-8-arginine vasopressin. Compared with the plasma values of healthy control children, levels of tissue-plasminogen activator (t-PA) antigen, plasminogen activator inhibitor type I (PAI-1) activity, and vWF as well as fibrin(ogen) degradation products were significantly elevated in the plasma of HUS patients on admission. No response of the fibrinolytic parameters and vWF were seen when 1-desamino-8-arginine vasopressin infusion was given on admission. After 2 wk, t-PA antigen and vWF had partially returned to basal values, and t-PA antigen increased rapidly again after 1-desamino-8-arginine vasopressin infusion. To investigate whether verocytotoxin contributes to the alteration of the fibrinolytic system found in HUS patients, purified verocytotoxin-1 (VT-1) was added to the media of cultured human endothelial cells. Addition of VT-1 alone did not change the production of t-PA, plasminogen activator inhibitor type I, and vWF antigen in these cells. However, when the endothelial cells were preincubated with tumor necrosis factor-alpha to increase the number of VT-1 receptors, VT-1 induced a marked decrease of the synthesis of t-PA, plasminogen activator inhibitor type I, and vWF. This was caused by a decrease in overall protein synthesis in the tumor necrosis factor-alpha- and VT-1-treated endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired homocysteine metabolism: a risk factor in young adults with atherosclerotic arterial occlusive disease of the leg.

To assess the prevalence of impaired homocysteine metabolism in young adults with arterial occlusive disease, 80 consecutive patients under 45 years old were screened. Various laboratory blood investigations and a standardized methionine loading test were performed. In the first 52 patients plasma levels of free homocysteine were determined; thereafter the levels of total homocysteine (a more sensitive measure of impaired homocysteine metabolism) were measured. The methionine loading test was abnormal in 15 patients (19 per cent) who did not differ from the other 65 with respect to prevalence of other risk factors, clinical characteristics, and electrocardiographic and angiographic findings. Blood levels of glucose, vitamins B6 and B12, folate, protein C and protein S, fibrinogen and low-density lipoprotein cholesterol did not differ significantly between the two groups. The prevalence of impaired homocysteine metabolism in young patients with arterial occlusive disease is greater than the 1-2 per cent found in the normal population.

Effects of labor and delivery on fibrinolysis.

Because timing of sampling is crucial in an investigation of the effects of labor and delivery on fibrinolysis we conducted a study of fibrinolytic markers in plasma of 10 healthy multiparous women in whom labor was induced, which allowed standardization of sampling times in relation to the course of labor and delivery. Blood samples were taken 5 min before the start of oxytocin infusion, at full cervical dilatation, and within 5 min after delivery of the placenta. A sample of mixed free flowing cord blood was obtained after delivery with the placenta in situ. Variables determined were tissue-type plasminogen-activator (t-PA) and the plasminogen activator inhibitors type 1 (PAI-1) and type 2 (PAI-2). The only significant change between the beginning of the induction of labor and the end of the first stage of labor was a rise in t-PA antigen (P = 0.01). All variables, except PAI-2 antigen, changed significantly after delivery of the placenta: t-PA antigen and activity showed a rise (P < 0.05), accompanied by a fall in PAI-1 antigen and activity (P < 0.01). T-PA activity in cord plasma was higher (P < 0.01) in comparison with maternal plasma concentrations at the end of the first stage of labor, t-PA antigen levels were similar, and PAI-1 antigen and activity and PAI-2 antigen were lower in cord plasma (P < 0.001). Our study shows that activation of the maternal fibrinolytic system can already be detected during labor, with a marked further increase in fibrinolytic potential after placental separation.

Prevention of adhesions.

A survey is given on the literature of the prevention of adhesions. Various methods of adhesion prevention are discussed: limitation of peritoneal injury, inhibition of the inflammatory response, prevention of coagulation of fibrinogen, removal of fibrin and mechanical separation of injured mesothelial surfaces.

Blood fibrinolysis and the response to desmopressin in glomerulonephritis.

Fibrinolytic parameters and von Willebrand factor (VWF) antigen were measured in 22 patients with glomerulonephritis (GN) who underwent renal biopsy after desmopressin (DDAVP) infusion. Blood was collected immediately before and after DDAVP infusion, after one week, and 3-6 months later. The main abnormalities on admission were the following: the mean baseline levels of t-PA antigen and VWF were significantly higher in GN patients than in 22 healthy controls; the median t-PA activity and the mean scu-PA level were significantly lower than normal. The t-PA response to DDAVP was impaired in 7 patients (32%), the response of VWF in 9 patients (41%), and the u-PA:Ag response in 11 patients (50%). When the patients were stratified according to creatinine clearance rate, significant differences between the subgroups with severely and moderately impaired renal function were noted: the baseline levels of PAI activity and VWF were higher in patients with severe renal failure and the VWF response to DDAVP was significantly lower. The response of u-PA (not of t-PA or VWF) to DDAVP appeared to correlate with urine flow during the first 24 h, suggesting the dependence of u-PA release on intact nephrons. A series of 18 patients with adult-type polycystic kidney disease (APKD) with creatinine clearance rates in the same abnormal range as the GN patients, had lower mean PAI and a significantly higher mean scu-PA level.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombin generation induced by the intrinsic or extrinsic coagulation pathway is accelerated by streptokinase, independently of plasminogen.

Thrombolytic therapy paradoxically induces the formation of fibrinopeptide A, fibrin degradation products and thrombin-antithrombin complexes, indicating thrombin generation. Part of the mechanism of this thrombin generation under the influence of thrombolytic agents was unraveled in this study. We measured thrombin with a chromogenic substrate at several time intervals after recalcification of citrated plasma which had been preincubated with urokinase, streptokinase, recombinant tissue plasminogen activator (rt-PA) or recombinant single-chain urokinase-type plasminogen activator (rscu-PA). Thrombin generation induced by the addition of thromboplastin together with calcium (extrinsic pathway) was greatly accelerated in the presence of streptokinase (from about 7 to 2 min), and to a lesser extent in the presence of urokinase, rt-PA or rscu-PA. Similar effects were seen after the addition of calcium to the plasma containing the thrombolytic agent and preincubated with partial thromboplastin (intrinsic pathway). Hirudin quenched the conversion of the chromogenic substrate completely, confirming that thrombin was the active enzyme. Aprotinine did not affect the results, and the effect of streptokinase was also observed in plasminogen-depleted plasma. We conclude that streptokinase, and to a lesser extent other thrombolytic agents, activate the prothrombinase complex directly or indirectly through a calcium-dependent mechanism, independently of plasminogen, with a resulting acceleration of thrombin generation.

Parameters of fibrinolysis in peritoneal fluid and plasma in different stages of the menstrual cycle.

The purpose of this study was to investigate differences in fibrinolytic activity in peritoneal fluid and plasma of women in the first and second part of the menstrual cycle. Given the classic concept of decreased fibrinolytic activity as a cause of adhesion formation, and if such differences are found, the stage of women's menstrual cycle should be taken into consideration when scheduling a laparotomy. We measured fibrinolytic parameters in peritoneal fluid and plasma in eight women in the pre-ovulatory period and in eleven women in the post-ovulatory period of the menstrual cycle. There were no differences in t-PA-Ag, t-PA-Act, u-PA-Ag and scu-PA concentrations in peritoneal fluid between the pre- and post-ovulatory group. Nevertheless, PAI-1-Ag in peritoneal fluid was three-fold higher in the post-ovulatory phase (p < 0.02). In peritoneal fluid the concentrations of both TDP and FbDP were three-fold higher at the same phase (p < or = 0.05). Plasma u-PA-Ag and scu-PA concentrations were significantly lower (30%, p < 0.05) in the post-ovulatory phase and also lower than plasma u-PA-Ag and scu-PA (measured with the same assay) in a group of 50 healthy individuals. No differences in t-PA and PAI concentration were found. In conclusion, the intraperitoneal fibrinolytic capacity might be impaired in the second part of the menstrual cycle, regarding the elevated levels of PAI-1-Ag, leading to an increased risk for post-ovulatory adhesion formation. The low plasma u-PA-Ag and scu-PA levels post-ovulatory may have clinical relevance.

1-Desamino-8-D-arginine vasopressin (DDAVP) in patients with congenital nephrogenic diabetes insipidus.

In healthy subjects, intravenous infusion of the selective V2-vasopressin receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP, 400 ng/kg in 10 min) causes a marked increase in heart rate with a slight decrease in diastolic blood pressure. These haemodynamic responses are associated with increments in the plasma levels of renin, noradrenaline (NA), clotting factor VIII (FVIII:C), von Willebrand factor (vWF:ag), and tissue-type plasminogen activator (t-PA), and a fall in the plasma level of plasminogen activator inhibitor (PAI). None of these changes was observed in 3 patients with congenital nephrogenic diabetes insipidus (NDI), who had a genetic defect of the V2-receptor. Plasma AVP levels in these patients were normal or slightly elevated, which makes it unlikely that the lack of DDAVP responsiveness was caused by down-regulation of vasopressin V1-receptors. In one NDI patient, arginine vasopressin (AVP) was given in incremental doses (62.5-4000 pg/kg/min). The heart rate and blood pressure responses to AVP were normal, indicating the absence of a V1-receptor defect. The responses of vWF:ag and t-PA to venous occlusion in the patients with NDI were similar to those in 5 healthy volunteers, which indicates that in NDI the endothelial release of both vWF:ag and t-PA is normal. We conclude that DDAVP causes its effects on heart rate and blood pressure, and on the plasma levels of renin, noradrenaline, FVIII:C, vWF:ag, and t-PA through V2-receptor stimulation.

The effect of ticlopidine upon plasma fibrinogen levels in patients undergoing suprapubic prostatectomy.

The mechanisms of the antithrombotic effect of the platelet aggregation inhibiting agent Ticlopidine might include a decrease of the plasma fibrinogen level. The effect of ticlopidine on increased fibrinogen synthesis following trauma, such as surgery, is however not known. 46 patients who underwent suprapubic prostatectomy were randomized to receive either (group A) Ticlopidine (2 x 250 mg daily) from the second preoperative day until the seventh postoperative day or (group B) placebo up till the day of surgery and further acenocoumarol against post-operatively and observed that the level and in particular the rise of the plasma fibrinogen concentration was not different in the two groups. It is concluded that compared with the standard treatment in group B ticlopidine does not influence trauma-induced fibrinogen increase.

Composition and susceptibility to thrombolysis of human arterial thrombi and the influence of their age.

Each of three distinct, concentric layers of human arterial thrombi, was analysed immunochemically for the plasminogen and fibrin content, and for the ex vivo susceptibility to thrombolysis by various thrombolytic agents in a saline or plasma milieu. The age of the thrombus layer determined: (a) the plasminogen content; (b) the fibrin content, inferred from the recovery of fibrin degradation products after complete lysis and from the binding of a monoclonal anti-fibrin antibody in a perfusion system, and (c) the lysibility of the thrombus. Plotting concentration of the various thrombolytic agents against percentage of lysis at several time points allows for reading of equivalent potencies of the respective units. Undiluted solutions of APSAC and rt-PA, prepared according to the manufacturer's directions, were less effective than diluted solutions, which has consequences for local therapy. All agents were at least as effective in saline as in a plasma milieu. We conclude that the plasminogen content of aged arterial thrombi is sufficient for complete and rapid thrombolysis. Only after several months do fibrin and plasminogen become so far degraded or replaced that the thrombi become resistant to thrombolysis.

The effects of aortic reconstruction and collagen impregnation of Dacron prostheses on the complement system.

Complement activation has been associated with numerous clinical hazards such as platelet aggregation, adult respiratory distress syndrome, and renal dysfunction. The complement system is activated by exposure of different biomaterials to blood. Recently a watertight knitted Dacron aortic prosthesis impregnated with bovine collagen has been developed. One potential disadvantage is that this bovine collagen may activate the complement system and evoke the production of inflammatory mediators. We conducted a prospective randomized trial to study the systemic effects of collagen-impregnated prostheses and of aortic surgery with implantation of Dacron prosthesis on the complement system in the perioperative period and at 3 months after operation. Forty-one patients randomly received either a collagen-impregnated (n = 20) or a nonimpregnated prosthesis (n = 21). Twelve patients who had cholecystectomy served as controls. CH50 consumption and C3a generation were determined to study overall complement activation. Furthermore, C3a/C3 fractions were calculated. Finally, C4 and factor B consumption were determined to evaluate the complement stimulation via the classic and the alternative pathways, respectively. We found significant activation of the complement system during the operation in both the collagen group (CH50 consumption: 40%, p = 0.03; C4 consumption: 74%, p < 0.0001; factor B consumption: 73%, p < 0.0001; C3a/C3 fraction increase: 173%,p = 0.04), and the nonimpregnated group (CH50 consumption: 40%, p < 0.0001; C4 consumption: 71%, p < 0.0001; factor B consumption: 76%, p < 0.0001; C3a/C3 fraction increase: 165%, p = 0.025), with no statistically significant differences between the groups of prostheses. Activation was initiated via both the classic and the alternative pathway. This indicates aortic implantation significantly activates the complement system, but that collagen-impregnated prostheses do not stimulate the complement system any more than its nonsealed substrate. Comparing results in patients with vascular disease with controls, a significantly increased complement activation was observed in the vascular group (CH50 consumption: 40%, p < 0.0001; C4 consumption: 74%, p < 0.0001; factor B consumption: 75%, p < 0.0001; C3a/C3 fraction: 169%, p = 0.002), compared with the controls (CH50 consumption: 71%; C4 consumption: 104%; factor B consumption: 94%; C3a/C3 fraction: 119%, all p = NS), with statistical significant differences between the vascular group and cholecystectomies (CH50: p = 0.005; C4: p = 0.002; factor B: p < 0.0001, and C3a/C3 fraction: NS). This observation demonstrates that aortic surgery with the implantation of a Dacron prosthesis significantly activates the complement system.

Peritoneal fluid and plasma fibrinolytic activity in women with pelvic inflammatory disease.

Previous studies have shown that the fibrinolytic activity of peritoneum is depressed in local inflammation. We measured fibrinolytic parameters in peritoneal fluid and in plasma of 10 women with pelvic inflammatory disease (PID). Nine women, in whom laparoscopy for sterilisation was performed, served as a control group. In the peritoneal fluid of women with PID, PAI-Ag, t-PA-Ag and u-PA-Ag were many times higher than in the control group. In contrast to the antigens which may be present in inert complexes, the potentially active compounds, measured as t-PA activity and plasmin-activable scu-PA, were not significantly different in the two groups, and in none of the samples was the active enzyme tcu-PA detectable. Nevertheless, the mean peritoneal fluid TDP and FbDP concentrations were about twenty times higher in the PID group than in the control group. In plasma of PID patients, none of the parameters except u-PA-Ag differed from those in the control group. The difference between control and patient plasma u-PA-Ag was statistically significant, but too small to attach any relevance to the observation. Our data suggest that, in contrast to the classical concept of decreased fibrinolytic activity as a cause of adhesion formation, intraperitoneal fibrinolysis is enhanced in peritoneal inflammation through stimulation of the local production of t-PA and u-PA. Despite concomitant production of PAI, fibrinolysis occurs at a high rate, resulting in high levels of fibrin degradation products. Since this activated fibrinolysis does not meet the demand, therapeutic enhancement should be considered to prevent adhesions.

Depression of tissue-type plasminogen activator and enhancement of urokinase-type plasminogen activator as an expression of local inflammation.

Inflammatory processes are accompanied by extravascular deposition and breakdown of fibrin. We measured fibrinolytic parameters in synovial fluid (SF) and in plasma of 36 patients with rheumatoid arthritis (RA). As a control, SF of 13 patients with blunt knee trauma, and plasma of 17 healthy volunteers were studied. In RA patients, extravascular t-PA mediated plasminogen activation was depressed: mean SF tissue-type plasminogen activator (t-PA:Ag) concentration (2.1 +/- 1.6 ng/ml) was four-fold lower, and plasminogen activator inhibitor (PAI) activity (284 +/- 212%) four-fold higher than the plasma values of the same patients or of healthy donors. In contrast, u-PA related plasminogen activation was strongly enhanced: urokinase-type plasminogen activator (u-PA) antigen (23.1 +/- 12.4 ng/ml) was more than four-fold higher, single-chain u-PA (scu-PA) (5.3 +/- 1.9 ng/ml) three-fold higher than in plasma of the same patients or of healthy donors, and active two-chain u-PA (tcu-PA) was detected in 14 of the 36 SF samples of RA patients. All of these changes in extravascular fibrinolytic parameters correspond with those induced by inflammatory mediators in cell cultures. In joint effusions of patients with a blunt knee trauma, the effects were intermediate: u-PA related parameters showed moderate changes in the same direction as in arthritis; t-PA antigen was also decreased. The only exception was that PAI was not increased. We conclude that the findings in traumatic effusions reflect transient effects as a reaction to trauma. In joint inflammation, the depressed t-PA mediated plasminogen activation, although more than compensated by the enhanced u-PA mediated plasminogen activation, results in protraction of fibrin removal. Besides, the enhanced u-PA activation might lead to proteolytic damage of the cartilage.

Plasminogen activators in synovial fluid and plasma from patients with arthritis.

The activity of plasminogen activators and inhibitors in the synovial fluid and plasma of patients with various forms of chronic arthritis was characterised. Tissue-type plasminogen activator antigen (t-PA:Ag), urokinase-type plasminogen activator antigen (u-PA:Ag), the proenzyme single chain u-PA (scu-PA), and plasminogen activator inhibitor (PAI) were measured in the synovial fluid and plasma of 22 patients with seropositive rheumatoid arthritis (RA), 13 with seronegative RA, and 23 patients with various forms of arthritis. In all patient groups the levels of t-PA:Ag in synovial fluid were lower and the levels of u-PA:Ag and PAI higher than plasma levels. Synovial fluid u-PA was more activated than plasma u-PA. Comparison of the patient groups showed that the largest differences between fibrinolytic parameters in synovial fluid and plasma were present in patients with seropositive RA followed by patients with seronegative RA and patients with various forms of arthritis. This order paralleled the functional and radiological scores of joint destruction in the patient groups studied. The results of this study indicate that suppression of t-PA production and enhancement of u-PA synthesis and activation in arthritic joints are associated with the clinical severity of arthritis.

The amount of plasminogen, tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in human thrombi and the relation to ex-vivo lysibility.

Thrombolytic therapy successfully reopens obstructed blood vessels in the majority of cases. However, it is not known why a substantial amount of thrombi are resistant to lysis by a fibrinolytic agent. In vitro studies have demonstrated that tissue-type plasminogen activator (t-PA) and plasminogen incorporated in the clot (during formation) increase lysibility. To test whether lysibility of in vivo formed human thrombi is related to their composition, we studied 25 venous thrombi obtained at autopsy and 21 arterial thrombi obtained during embolectomy. Plasminogen activator inhibitor-1 (PAI-1) antigen was measured in a phosphate-buffered saline (PBS) extract of each thrombus; t-PA antigen and plasminogen antigen were determined in a 6 M urea extract of the thrombus, representing bound proteins. Lysibility was measured as weight reduction during 8 h of incubation in PBS containing streptokinase (SK) 100 U/ml, corrected for spontaneous lysis, reflected by weight loss in PBS without SK. In addition, lysibility in SK was compared with lysibility in urokinase (UK) 100 U/ml and in t-PA 200 U/ml. Spontaneous lysis amounted to 29 +/- 5% (mean +/- SEM) and 33 +/- 5% in venous and arterial thrombi, respectively, and inversely correlated with the PAI-1 content of thrombi (r = -0.43, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic effects of collagen-impregnated aortoiliac Dacron vascular prostheses on platelet activation and fibrin formation.

To minimize intraoperative blood loss a watertight knitted Dacron aortoiliac prosthesis has been developed by impregnation with bovine collagen. A potential disadvantage is that collagen may be associated with an increase in thrombus formation. We conducted a prospective randomized trial to study the systemic effects of collagen-impregnated prostheses and of aortoiliac operation as such on the coagulation mechanism during the first 10 days after operation. Forty-one patients randomly received either a collagen-impregnated (n = 20) or a nonimpregnated prosthesis (n = 21). Twelve patients who underwent cholecystectomies served as controls. Three markers of the coagulation mechanism were monitored: beta-thromboglobulin, fibrinopeptide A, and fibrin/fibrinogen degradation products. We found no significant differences in median beta-thromboglobulin, fibrinopeptide A, and fibrin/fibrinogen degradation product levels between patients in the collagen-impregnated prosthesis group and patients in the nonimpregnated prosthesis group. This indicates that collagen does not stimulate the coagulation cascade any more than conventional Dacron protheses do. In a comparison of patients who underwent aortoiliac reconstruction and patients who underwent cholecystectomies, the results indicated a significant increased platelet activation and fibrin metabolism in aortoiliac reconstruction group compared with the control group. Finally, we observed a significantly higher preoperative fibrin metabolism in patients with vascular disease than in control subjects. This difference is attributable to the high preoperative fibrin/fibrinogen degradation product values in patients with aortic aneurysms.