THE EFFECT OF PHYSICAL CONDITIONING SUGGESTS ADAPTATION IN PROCOAGULANT AND FIBRINOLYTIC POTENTIAL

Acute exercise evokes a transient increase in procoagulant activity. We evaluated the effect of physical conditioning on the activation of the coagulation and fibrinolytic systems. Two groups of subjects of different aerobic endurance levels (athletes and controls with maximal oxygen uptake (VO_{2 max}) 68,4 and 52,6 ml·kg⁻¹·min⁻¹, respectively), were tested at rest and after standardized exercise at 80 % of their individual VO_{2 max}. There was a significant increase in prothrombinfragment 1+2 (F1+2) level among controls in response to standardized exercise (p<0.05), whereas no significant difference in the level of F1+2 between athletes and controls at rest or in response to exercise was demonstrated. Tissue plasminogen activator (tPA) antigen level at rest was significantly lower in athletes compared to controls (p<0.03). A significant increase was found in the tPA level after standardized exercise in both groups (p<0.02), which was lower in athletes compared to controls (p<0.05). There were no significant differences between athletes and controls in plasminogen activator inhibitor-1 (PAI-1) and thrombin antithrombin complex (TAT) levels at rest. Athletes had a significantly lower PAI-1 level than controls after exercise (p<0.05). In conclusion, the present study suggests an increased activation of the coagulation system in response to exercise in controls only. It also suggests adaptive changes in fibrinolytic potential induced by physical conditioning, as demonstrated by the lower level of tPA at rest and the lower levels of tPA and PAI-1 after exercise in athletes compared to controls. © 1997 Elsevier Science Ltd     

Improved fibrinolysis after 1-year treatment with HMG CoA reductase inhibitors in patients with coronary heart disease

The study was aimed to investigate the effect of two different statins on the levels of haemostatic variables reflecting procoagulant and fibrinolytic activity in patients with coronary heart disease (CHD), with the hypothesis that statins might beneficially modify these levels. Fifty-eight patients were randomized to treatment with atorvastatin (n=28) or simvastatin (n=30) for 1 year. The starting dose in both groups was 20 mg/day. Fasting blood samples were collected before and after 12-month treatment for determinations of fibrinogen, prothrombin fragment 1+2 (F1+2), plasma D-dimer, soluble tissue factor, tissue plasminogen activator (tPA) antigen, tPA activity, plasminogen activator inhibitor type-1 activity (PAI-1 activity) and serum D-dimer as a global test of fibrinolytic activity. In the total population, improved fibrinolytic activity was observed after 1 year with increased levels of serum D-dimer (P=.001) and tPA activity (P=.024) and a reduction in tPA antigen (P=.048). No statistically significant changes were observed in any of the measured coagulation variables. Separately examined, an improved fibrinolytic profile was seen in the atorvastatin group with a significant increase in serum D-dimer (P=.005), a borderline increase in tPA activity (P=.083) and a borderline reduction in tPA antigen (P=.069). Within the simvastatin group, a reduction in prothrombin F1+2 was observed (P=.038). The differences in changes between the groups were statistically significant only for global fibrinolysis (serum D-dimer, P=.046). In conclusion, an improved fibrinolytic profile was observed after statin treatment, most pronounced with atorvastatin. The results indicate that the drugs promote a profibrinolytic profile, and may in part explain the benefit of statin treatment rendered in the prevention of CHD.     

Fibrinolytic proteins and progression of coronary artery disease in relation to gemfibrozil therapy

Impaired fibrinolytic function, mainly due to increased plasma plasminogen activator inhibitor-1 (PAI-1) activity, is common in patients with manifest coronary artery disease (CAD) and a predictor of recurrent cardiovascular events. We investigated the relationships of plasma tissue-type plasminogen activator (tPA) and PAI-1 antigen levels, plasma PAI-1 activity and PAI 4/5-guanosine (4G/5G) genotype to CAD progression in 203 middle-aged men participating in the Lopid Coronary Angiography Trial (LOCAT). A higher tPA antigen concentration, whether baseline or on-trial, was associated with a more severe global angiographic response (p < 0.05), an association mainly accounted for by progression of diffuse lesions in graft-affected segments (change in per-patient means of average diameters of segments haemodynamically related to bypass grafts). Plasma PAI-1 activity and mass concentration and 4G/5G PAI-1 genotype were unrelated to angiographic outcome measurements. tPA and PAI-1 antigen increased significantly in the gemfibrozil group (+11.3% and + 16.4%, respectively, p < 0.001), whereas there was no treatment effect on PAI-1 activity (median change 0.0%). It is concluded that fibrinolytic function does not substantially influence progression of CAD as assessed by angiography in middle-aged men. Furthermore, pronounced long-term lowering of serum triglycerides by gemfibrozil treatment does not significantly affect the plasma PAI-1 activity level but increases the plasma tPA and PAI-1 antigen concentrations.     

Short-term effect of surgical trauma on rat peritoneal fibrinolytic activity and its role in adhesion formation

BACKGROUND: Fibrin deposition, the primary step in the formation of post-surgical adhesions, is the result of a disbalance between the fibrin-forming and the fibrin-dissolving capacity of the peritoneum. Literature data suggest a transient reduction in local plasminogen activator activity after peritoneal trauma, which results in a reduction of fibrinolysis and permits deposited fibrin to become organized into fibrous, permanent adhesions. In the present study, the fibrinolytic parameters tissue-type plasminogen activator (tPA; antigen and activity) and plasminogen activator inhibitor type-1 (PAI-1; antigen and activity) were measured in peritoneal fluid, in peritoneal biopsies and in plasma to establish the time course of changes in fibrinolytic activity. DESIGN: A standardized peritoneal adhesion model in the rat. OUTCOME MEASURES: Analysis, over a 72-h period following surgical trauma. of the main fibrinolytic parameters in peritoneal lavage, in biopsies of damaged and undamaged peritoneum, and in plasma, and determination of fibrin and fibrin(ogen)-degradation products in peritoneal lavage fluid. RESULTS: At all time intervals, tPA antigen was found to be about six-fold increased in peritoneal lavage after surgical trauma. This significant rise in tPA antigen was accompanied by a large increase in its main inhibitor PAI-1, resulting in tPA activity levels similar to, or slightly higher than, those found in control animals. tPA activity was lowest at 4 h and increased thereafter. Also in biopsies from damaged peritoneum, tPA antigen was significantly increased. Tissue tPA activity was also lowest at 4 h, after which it increased, significantly so at 24 and 72 h. Similar, though smaller, changes were seen in the biopsies from undamaged areas of the peritoneal wall in operated rats. PAI-1 (antigen and activity) was not detected in peritoneal biopsies. Fibrin-related material (especially fibrin monomer/fibrinogen, an indicator of forming fibrin) in peritoneal fluid was slightly increased at 4 h, and abundantly present at 16 and 24 h, returning to control levels at 72 h. Fibrin degradation products were always present. From 2 h onward, adhesions were found. CONCLUSIONS: In contrast to the view that adhesions are formed as a result of a reduced fibrinolytic activity, our results demonstrate that tPA activity remained unchanged or slightly increased after surgical trauma, and point to increased fibrin formation rather than diminished fibrinolytic activity as the main cause of fibrin deposition after peritoneal trauma. Therapies directed at prevention of adhesion formation should therefore aim at avoiding massive fibrin production and at promoting fibrinolytic activity during the early period after trauma.     

A randomised, controlled study of the effects of aerobic exercise and dietary fish on coagulation and fibrinolytic factors in type 2 diabetics

Type 2 diabetes is associated with disturbances in coagulation and fibrinolysis. Prospective studies show that increased tissue plasminogen activator (tPA) antigen increases the risk of cardiovascular mortality. The present study examined the hypothesis that combining a regime of moderate aerobic exercise with one daily fish meal as part of a low-fat diet (30% total energy) would improve coagulation and fibrinolytic factors in dyslipidaemic type 2 diabetic patients. In a randomised. controlled, 8-week trial, 55 sedentary type 2 diabetic subjects with serum triglycerides >1.8 mmol/l and/or HDL-C <1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g omega3 fatty acids/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate <100 bpm) exercise program. Plasma levels of fibrinogen, coagulation factor VIIc, tPA and plasminogen activator inhibitor (PAI-1) antigen were measured before and after intervention. In the 49 subjects who completed the study, the fish diet alone, moderate exercise alone and the combination of fish and moderate exercise all led to significant reductions in tPA antigen concentrations (-2.1 ng/ml, p = 0.02. -1.9 ng/ml, p = 0.03, -2.0 ng/ml, p = 0.01, respectively) compared to controls. In multivariate regression, changes in fasting blood glucose (positively) and erythrocyte omega3 fatty acid composition (inversely) were independent predictors of the change in tPA antigen. The fish diet alone contributed to a significant rise in coagulation factor VIIc compared to controls (4.9%, p = 0.02), which was prevented by moderate exercise. No significant effects on PAI-1 antigen and fibrinogen were seen. In view of recent epidemiological findings, the reduction in tPA antigen with both fish and moderate exercise in these dyslipidaemic type 2 diabetic patients could reflect a reduced thrombotic potential and decreased cardiovascular risk. Furthermore, a small, albeit significant, increase in coagulation factor VIIc associated with fish can be prevented by a concomitant programme of moderate exercise.     

Impaired fibrinolysis and postoperative thromboembolism in orthopedic patients.

The incidence of deep vein thrombosis (DVT) and pulmonary embolism was studied prospectively in patients undergoing elective total hip replacement. 96 patients were randomly allocated to receive either low molecular weight heparin (LMWH) or unfractionated heparin (UFH). All patients had bilateral phlebography and pulmonary perfusion/ventilation scintigraphy 10-12 days after surgery. The following fibrinolytic variables were analysed in plasma and related to thromboembolism: tissue plasminogen activator (t-PA) activity, t-PA antigen (t-PA Ag), plasminogen activator inhibitor (PAI-1) activity and PAI-1 antigen (PAI-1 Ag). No significant difference was found, regarding the fibrinolytic response to surgery, between patients treated with LMWH and UFH. The level of PAI-1 activity was significantly increased before operation in patients developing DVT as compared to non-DVT patients (p less than 0.03). Immediately after surgery and in the morning the first postoperative day the levels of PAI-1 activity, PAI-1 Ag and t-PA Ag were positively correlated to thromboembolism. PAI-1 activity was the only preoperative fibrinolytic variable correlated to thromboembolism.     

Changes in fibrinolysis following exercise above and below lactate threshold

This study sought to compare fibrinolytic responses to exercise above lactate threshold (LT) to longer-duration, equicaloric exercise below LT. Fifteen males performed cycle ergometer tests above (77% VO(2)peak) and below LT (41% VO(2)peak) to comparatively evaluate tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) responses. tPA activity significantly (P < 0.05) increased during the >LT test (pre-exercise = 1.57 +/- 0.44 IU ml(-1), post-exercise = 3.85 +/- 4.72 IU ml(-1)), but not the LT (pre-exercise = 8.32 +/- 4.48 ng ml(-1), post-exercise = 14.23 +/- 5.40 ng ml(-1)) and LT test. PAI-1 activity significantly (P < 0.05) decreased during both the >LT (pre-exercise = 15.00 +/- 2.73 AU ml(-1), post-exercise = 10.12 +/- 2.90 AU ml(-1)) and LT test. Our results suggest that exercise 相似文献   

Fluctuation of tPA and PAI-1 antigen levels in plasma: difference of their fluctuation patterns between male and female

The circadian fluctuation of the fibrinolytic activity and the antigen levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in plasma were analyzed in normal male and female volunteers. Samples were obtained at 8:30, 10:30, 12:30, 14:30 and 16:30 h. Euglobulin clot lysis time (ECLT) showed the longest time at 8:30 to 10:30 h and the shortest time at 16:30 h. The highest level of tPA was obtained at 8:30 h and the lowest at 14:30 h in men, whereas the highest value was at 8:30 h and the lowest was at 16:30 h in females. Free PAI-1 showed highest value at 10:30 h in men and at 8:30 h in women. The lowest values obtained at 16:30 h in both men and women and were about one third of the highest values. ECLT was always shorter in females than in males and parameter such as tPA and PAI-1 were also lower in females than in males. The phase of the circadian rhythm of the fibrinolytic parameters may be advanced in females than in males.     

Relationship between maternal and cord blood hemostatic disturbances in preeclamptic pregnancies

Endothelial cell activation or damage is believed to play a key role in preeclampsia (PE) and may underlie the hemostatic changes observed in this syndrome. The aim of this study was to evaluate a relationship between maternal and cord blood hemostatic disturbances in preeclamptic pregnancies. We measured the plasma levels of tissue plasminogen activator (tPA) antigen and of plasminogen activator inhibitor type 1 (PAI-1) antigen, both markers of hemostatic and endothelial function, and fibrin fragment D-dimer. Maternal blood from uncomplicated (n = 42) and PEc pregnancies (n = 44) were collected before delivery, and umbilical cord blood (UCB) immediately after delivery.In preeclamptic cases, UCB presented significantly higher tPA values and significantly lower PAI-1/tPA ratio. Preeclamptic women also presented significantly higher tPA, as well as PAI-1 values, when compared with normal pregnant women; no significant difference was found for D-dimer. In preeclamptic women, proteinuria (a marker of PE severity) correlated positively and significantly with tPA and PAI-1 antigen levels. An inverse relationship between maternal tPA antigen levels and fetal birth weigh in PE was also observed.Our data show that the hemostatic maternal disturbances observed in preeclamptic women have similarities with the UCB circulation, and that endothelial dysfunction is the most plausible underlying cause. Moreover, maternal hemostatic disturbances seem to be associated with the severity of PE. Further studies are needed to strength the values of tPA and PAI-1 as markers of severity in PE.     

Coagulation and fibrinolysis during laparoscopic cholecystectomy

Laparoscopic surgery appears to be less traumatic to the patient than open surgery, but its influence upon coagulation and fibrinolysis is incompletely elucidated. Our aim was to measure markers of coagulation and fibrinolysis before, during. and after laparoscopic cholecystectomy (LC). Blood samples drawn on admission, on four occasions during operation as well as 2 hours after operation and on the first postoperative day in 50 patients undergoing elective LC were analyzed for prothrombin fragment 1+2 (F1+2), soluble fibrin (SF), D-dimer (DD), fibrin degradation products (FbDP), tissue-type plasminogen activator (tPA) activity and antigen, and plasminogen activator inhibitor (PAI) activity and antigen. F1+2, SF, DD, and FbDP levels increased significantly after LC. Differences between pre- and postoperative PAI and tPA levels were not significant apart from a transient increase in tPA antigen levels. tPA activity was significantly increased during operation.     

TM5275 prolongs secreted tissue plasminogen activator retention and enhances fibrinolysis on vascular endothelial cells

Introduction

Elevated plasminogen activator inhibitor-1 (PAI-1) reduces fibrinolytic potential in plasma, contributing to thrombotic disease. Thus, inhibiting PAI-1 activity is clinically desirable. We recently demonstrated that tissue plasminogen activator (tPA) remains on the surface of vascular endothelial cells (VECs) after secretion in a heavy-chain dependent manner, which is essential for high fibrinolytic activity on the surface of VECs, and that PAI-1 dissociates retained tPA from the cell surface as a result of high-molecular weight complex formation. Based on the model whereby amounts of tPA and its equilibrium with PAI-1 dynamically change after exocytosis, we examined how TM5275, a newly synthesized small molecule PAI-1 inhibitor, modulated tPA retention and VEC surface-derived fibrinolytic activity using microscopic techniques.

Materials and methods

The effects of TM5275 on the kinetics of the secretion and retention of green fluorescent protein (GFP)-tagged tPA (tPA-GFP) on VECs were analyzed using total internal reflection fluorescence microscopy. The effects of TM5275 on the generation of plasmin activity were evaluated by both plasminogen accumulation and fibrin clot lysis on tPA-GFP-expressing VECs using confocal laser scanning microscopy.

Results

TM5275 at concentrations of 20 and 100 μM significantly prolonged the retention of tPA-GFP on VECs by inhibiting tPA-GFP-PAI-1 high-molecular-weight complex formation. TM5275 enhanced the time-dependent accumulation of plasminogen as well as the dissolution of fibrin clots on and around the tPA-GFP-expressing cells.

Conclusions

The profibrinolytic effects of TM5275 were clearly demonstrated by the prolongation of tPA retention and enhancement of plasmin generation on the VEC surface as a result of PAI-1 inhibition.     

Fluctuation of TPA and PAI-1 antigen levels in plasma: difference of their fluctuation patterns between male and female

The daytime fluctuation of the fibrinolytic activity and the antigen levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in plasma were analyzed in normal male and female volunteers. Samples were obtained at 8:30, 10:30, 12:30, 14:30 and 16:30 h. Euglobulin clot lysis time (ECLT) showed the longest time at 8:30 to 10:30 h and the shortest time at 16:30 h. The highest level of tPA was obtained at 8:30 h and the lowest at 14:30 h in men, whereas the highest value was at 8:30 h and the lowest was at 16:30 h in females. Active free PAI-1 showed highest value at 10:30 h in men and at 8:30 h in women. The lowest values obtained at 16:30 h in both men and women and were about one third of the highest values. ECLT was always shorter in females than in males and parameter such as tPA and PAI-1 were also lower in females than in males. The phase of the circadian rhythm of the fibrinolytic parameters may be advanced in females than in males.     

Systematic elucidation of effects of tranexamic acid on fibrinolysis and bleeding during and after cardiopulmonary bypass surgery.

The aim of this study was to systematically elucidate the effects of tranexamic acid on fibrinolysis and bleeding during and after cardiopulmonary bypass (CPB) surgery. Twenty-two patients undergoing CPB surgery were randomized to receive 100 mg/kg tranexamic acid or an equal volume of saline after anesthesia induction and prior to skin incision. Plasma levels of tissue plasminogen activator (t-PA) antigen and activity, crosslinked fibrin degradation products (D-dimer), alpha2-antiplasmin-plasmin complex, and plasminogen activator inhibitor-1 (PAI-1) antigen were measured. Blood samples were obtained after induction of anesthesia, before, during, and after CPB, at the end of surgery, and the next morning after surgery. Intraoperative and postoperative blood loss during 24 h after surgery was recorded. Patients' demographics were similar between the two groups. No patients suffered from thrombotic complications after surgery. In the tranexamic acid group, fibrinolytic activity and secondary fibrinolysis as measured by t-PA activity and D-dimer were markedly suppressed during CPB surgery (P=.042 and P=.015, respectively). Decreased fibrinolytic activity and fibrinolysis were accompanied by reduction of perioperative bleeding in the tranexamic acid group. We could also find a good positive correlation between the peak levels of t-PA activity and D-dimer (r(2)=.4203, P=.0011). No differences in the t-PA antigen, PAI-1 antigen release, and plasmin inhibition by alpha2-antiplasmin were apparent between the two groups. In a randomized, prospective trial of patients undergoing CPB surgery, we demonstrated that the synthetic antifibrinolytic drug tranexamic acid effectively suppresses fibrinolysis by inhibiting t-PA and plasmin activity with clear reduction of perioperative blood loss. While tranexamic acid had no effects on the other important fibrinolytic inhibitors like PAI-1 and alpha2-antiplasmin.     

Plasminogen Activation Without Changes in tPA and PAI-1 in Response to Subcutaneous Administration of Ancrod

Ancrod is a purified fraction of venom from the Malayan pit viper, Calloselasma rhodostoma, currently under investigation for treatment of ischemic stroke. The therapeutic effect is ascribed to a lowering of plasma fibrinogen. Thirty-two healthy volunteers received subcutaneous ancrod at doses of 1.0, 1.5 and 2.0 IU/kg body weight or placebo. Blood samples were drawn before the injection and at various time points until 96 h after the injection. Ancrod leads to the formation of desAA-fibrin, which serves as cofactor in tissue plasminogen activator activity (tPA)-induced plasminogen activation. Unchanged concentrations of prothrombin fragment F1.2 and thrombin–antithrombin complex (TAT) indicate that fibrin formation occurs independent of thrombin. Plasmin generation is independent of an increase in tPA activity or changes in plasminogen activator inhibitor-1 (PAI-1) concentration in plasma. Subcutaneous injection of ancrod leads to a generalized fibrino(geno)lytic response caused solely by providing tPA with soluble fibrin as its cofactor in plasminogen activation. Maximal plasmin activity is present 12 h after subcutaneous injection.     

Fibrinolysis in normal subjects--comparison between plasminogen activator inhibitor and other components of the fibrinolytic system

We analyzed fibrinolytic parameters in 20 healthy men and 20 healthy women, aged from 25 to 59, before and after 10 and 20 min venous occlusion. The 10 min post-occlusion fibrinolytic activity measured directly in diluted unfractionated plasma by a highly sensitive 125I-fibrin plate assay correlated well with the activity of euglobulins determined by the classical fibrin plate assay (r = 0.729), but pre-stasis activities determined with these two methods did not correlate (r = 0.084). The enhancement of fibrinolytic activity after venous occlusion was mainly due to an increase of t-PA in the occluded vessels (4-fold increase t-PA antigen after 10 min and 8-fold after 20 min venous occlusion). Plasminogen activator inhibitor (PAI) activity and plasminogen activator inhibitor 1 (PAI-1)1 antigen levels at rest showed considerable dispersion ranging from 1.9 to 12.4 U/ml, respectively 6.9 to 77 ng/ml. A significant increase of PAI-1 antigen levels was observed after 10 and 20 min venous occlusion. At rest no correlation was found between PAI activity or PAI-1 antigen levels and the fibrinolytic activity measured by 125I-FPA. However, a high level of PAI-1 at rest was associated with a high prestasis antigen level of t-PA and a low fibrinolytic response after 10 min of venous stasis. Since the fibrinolytic response inversely correlated with PAI activity at rest, we conclude that its degree depends mainly on the presence of free PAI.     

Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives

The effect of oral contraceptives (OC) on fibrinolytic parameters was investigated in a cycle-controlled cross-over study in which 28 non-OC using women were randomly prescribed either a representative of the so-called second (30 microg ethinylestradiol, 150 microg levonorgestrel) or third generation OC (30 microg ethinylestradiol, 150 microg desogestrel) and who switched OC after a two month wash out period. During the use of OC, the levels of tissue-type plasminogen activator (tPA) activity, plasminogen, plasmin-alpha2-antiplasmin complexes and D-dimer significantly increased (by 30 to 80%), while the levels of plasminogen activator inhibitor- (PAI-1) antigen, PAI-1 activity and tPA antigen significantly decreased (25 to 50%), suggesting an increase in endogenous fibrinolytic activity. These OC-induced changes were not different between the two contraceptive pills. TAFI (thrombin-activatable fibrinolysis inhibitor) levels increased on levonorgestrel, and even further increased on desogestrel. A clot lysis assay that probes both fibrinolytic activity and the efficacy of the coagulation system to generate thrombin necessary to down regulate fibrinolysis via TAFI showed no change of the clot lysis time during OC use. This finding suggests that the OC-induced increase in endogenous fibrinolytic activity is counteracted by an increased capacity of the coagulation system to down regulate fibrinolysis via TAFI. Indeed we observed that during OC use there was a significant increase of F1+2 generation during clot formation. When these assays were performed in the presence of an antibody against factor XI, we observed that the clot lysis time was significantly increased during OC use and that the increase in F1+2 generation during OC therapy was due to a factor XI-independent process, which was significantly higher on desogestrel than on levonorgestrel. These data indicate that the OC-induced inhibition of endogenous fibrinolysis takes place in a factor XI-independent way and is more pronounced on desogestrel than on levonorgestrel-containing OC.     

Serial changes in fibrinolysis and coagulation activation markers in acute and convalescent phase of ischemic stroke

BACKGROUND: The changes in the activity of a number of plasma markers of coagulation and fibrinolysis have previously been studied in patients with ischemic stroke, with conflicting results. We aimed to find out the changes in the activities of a wide array of markers of the coagulation and the fibrinolytic system of mildly or moderately affected first-ever ischemic stroke patients. METHODS: In a prospective, longitudinal, case-control study, we studied plasma plasminogen activator inhibitor type-1 (PAI-1) activity, tissue-type plasminogen activator antigen (t-PA:Ag), d-dimer, prothrombin fragment 1+2 (F 1+2), and thrombin-antithrombin III complex (TAT) levels in 55 consecutive patients on admission, 1 week, 1 month, and 3 months after an ischemic stroke. Sex- and age-matched controls were studied once. All patients underwent blood sampling at each study time point; comprehensive stroke risk factors were recorded, and the etiology of the ischemic stroke was determined. All patients were contacted 3 years later for possible recurrent ischemic events. RESULTS: PAI-1 activity was increased in the acute phase and at 3 months, D-dimer levels were significantly higher at 1 week and 1 month after stroke, whereas t-PA:Ag, TAT and F 1+2 levels remained stable during the whole study period. CONCLUSIONS: The changes of the fibrinolytic and coagulation system activity in the patients with mild or moderate ischemic stroke appeared minor compared with the results of previous studies, which included more severely ill patients.     

Are haemostatic and fibrinolytic parameters predictors of preeclampsia in pregnancy-associated hypertension?

The plasma levels of several haemostatic and fibrinolytic parameters were measured before and after delivery in 61 hypertensive pregnant women of whom 22 developed preeclampsia, and compared to the results obtained in 42 normal pregnant women. In the two last weeks before delivery (D less than or equal to -15) tPA antigen, PAI-1 activity, vWF:Ag/FVIII:C ratio, ATIII activity and platelet count were found to be significantly different in the hypertensive pregnant women with and without preeclampsia. Combined all together, an association of three of these five parameters were found to be pathological (i.e.:tPA:Ag greater than or equal to 19 ng/ml, PAI-1 activity greater than or equal to 58 IU/ml, vWF:Ag/FVIII:C ratio greater than or equal to 2.6, ATIII activity less than or equal to 73%) in none of the hypertensive women without preeclampsia and in only 35% of the preeclamptic group. A positive correlation was demonstrated between vWF:Ag/FVIII:C ratio and tPA:antigen levels suggesting that both tPA and vWF:Ag could be considered as early indicators of a possible micro angiopathy occurring in preeclampsia. However, due to the high dispersion of the results, it appears that the investigated haemostatic and/or fibrinolytic criteria give only presumptive arguments before assigning risk for preeclampsia development among hypertensive pregnant women.     

Hemostatic alterations in patients with benign and malignant colorectal disease during major abdominal surgery.

We determined sensitive markers of coagulation and fibrinolysis in plasma of 20 patients with malignant colorectal disease as compared to 17 patients with benign colorectal disease. Thrombin/antithrombin III complex (TAT), soluble fibrin (SF), total fibrinogen and fibrin degradation products (TDP), plasminogen activator inhibitor type-1 (PAI-1), urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) were measured preoperatively, starting anesthesia, during surgery and postoperatively. The purpose was to verify the supposed hypercoagulable state of cancer patients. In addition, we investigated whether the hemostatic alterations induced by general anesthesia and major abdominal surgery differed between the two groups. Patients with colorectal cancer showed initially an altered balance of hemostasis with a preponderance of procoagulant activity and fibrinolytic inhibition, as noted by marginally elevated TAT and PAI-1 plasma levels. The stimulus of anesthesia induction alone was sufficient to trigger not only activation of coagulation in these patients but also further activation of fibrinolysis and increased fibrinolytic inhibition. The marked activation of coagulation and fibrinolysis and enhanced fibrinolytic inhibition during surgery was more pronounced in patients with malignancy as compared to the control group. Postoperatively, a shift of the normal balance of hemostasis with a slight preponderance of fibrinolytic inhibition was observed, as evidenced by a marginally elevated PAI-1 plasma levels. The results of this study strengthen the hypothesis of a hypercoagulable state in patients with colorectal malignancy that may favor the development of thrombosis in this patient group.     

Short-chain fatty acid enemas stimulate plasminogen activator inhibitor-1 after abdominal aortic graft surgery: a double-blinded, placebo-controlled study

Colonic ischaemia may complicate aortic graft surgery with high mortality from associated colonic necrosis. Loss of the mucosal barrier function due to ischaemia may promote translocation of endotoxins with secondary systemic disseminated coagulation leading to multiple organ failure. Short-chain fatty acids (SCFAs) stimulate the microcirculation in the human rectum. The aim of this study was to investigate whether SCFA enemas influence systemic endotoxinaemia and fibrinolytic activity during and after elective aortic graft surgery for arteriosclerosis. Thirty-two patients were randomized to SCFA or placebo enemas twice daily from the day before surgery to 7 days after. Blood samples for endotoxin, plasminogen activator inhibitor-1 (PAI-1) activity, tissue-type plasminogen activator (t-PA) antigen, and cross-linked fibrin degradation products (XL-FDP) were drawn before, during, and 7 days after surgery. Four patients, two in each treatment group, developed postoperative endotoxinaemia. PAI-1 was significantly higher on days 2 and 4 in SCFA-treated patients, whereas t-PA was comparable Petween the groups. During the postoperative course, a progressive and near-identical XL-FDP increase was found in the two groups. In elective aortic graft surgery for arteriosclerosis, SCFA enemas likely stimulate systemic PAI-1 activity by promoting colonic tissue reperfusion following aortic unclamping. Endotoxinaemia and fibrinolytic shutdown are uncommon findings.