Fibrinolytic Response Research Articles

Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia inhibits fibrinolysis during human endotoxemia

AbstractType 2 diabetes is associated with altered immune and hemostatic responses. We investigated the selective effects of hyperglycemia and hyperinsulinemia on innate immune, coagulation, and fibrinolytic responses during systemic inflammation. Twenty-four healthy humans were studied for 8 hours during clamp experiments in which either plasma glucose, insulin, both, or none was increased, depending on randomization. Target plasma concentrations were 5 versus 12 mM for glucose, and 100 versus 400 pmol/L for insulin. After 3 hours, 4 ng/kg Escherichia coli endotoxin was injected intravenously to induce a systemic inflammatory and procoagulant response. Endotoxin administration induced cytokine release, activation of neutrophils, endothelium and coagulation, and inhibition of fibrinolysis. Hyperglycemia reduced neutrophil degranulation (plasma elastase levels, P < .001) and exaggerated coagulation (plasma concentrations of thrombin-antithrombin complexes and soluble tissue factor, both P < .001). Hyperinsulinemia attenuated fibrinolytic activity due to elevated plasminogen activator-inhibitor-1 levels (P < .001). Endothelial cell activation markers and cytokine concentrations did not differ between clamps. We conclude that in humans with systemic inflammation induced by intravenous endotoxin administration hyperglycemia impairs neutrophil degranulation and potentiates coagulation, whereas hyperinsulinemia inhibits fibrinolysis. These data suggest that type 2 diabetes patients may be especially vulnerable to prothrombotic events during inflammatory states.

Intra‐aortic Balloon Pump‐induced Pulsatile Flow Reduces Coagulative and Fibrinolytic Response to Cardiopulmonary Bypass

The aim of this study is to evaluate if a simple intra-aortic balloon pump (IABP)-induced pulsatile perfusion reduces activation of coagulative system during cardiopulmonary bypass (CPB). Ninety-six patients undergoing preoperative IABP were randomized to nonpulsatile CPB with IABP discontinued during cardioplegic arrest (Group A) or IABP-induced pulsatile CPB (Group B). White blood cells (WBC), hematocrit (Ht), platelets (PLTs), International Normalized Ratio (INR), fibrinogen, activated partial thromboplastin time (aPTT), antithrombin III (AT-III) activity, and D-dimer were measured at the end of surgery (ES) and postoperatively. Chest drainage, need for reexploration, and transfusions were compared. Group B showed lower chest drainage (1st day P = 0.038; 2nd day P = 0.044), transfusions (P = 0.031), WBC (P < 0.05 at all time points), and INR (P < 0.05 at all time points), together with a higher Ht (P < 0.05 at ES, 12 h), platelets (P < 0.04 at all time points), fibrinogen (P < 0.05 at ES, 12 h, 24 h), and aPTT (P < 0.05 at all time points). AT-III activity lowered in Group A (P = 0.001 at ES, 12 h, 24 h), together with higher D-dimer levels (P < 0.05 at all time points). IABP-induced pulsatile perfusion ameliorates coagulative system activation following CPB.

Exercise-induced hemostatic activation in patients with dilated cardiomyopathy in sinus rhythm

Abnormalities of baseline hemostatic variables have been related to a hypercoagulable state in patients with chronic heart failure (CHF). Given that physical exercise leads to an activation of coagulation physiologically, this study addressed the question of whether the exercise-induced hemostatic activation is enhanced in patients with CHF. Ten patients with dilated cardiomyopathy (ejection fraction < 40%) and 10 healthy individuals (matched for sex, age and body mass index) were subjected to a maximal exercise test on a bicycle ergometer. Healthy subjects performed a second exercise test at a submaximal intensity level, in which oxygen consumption (VO2) was adjusted to the peak oxygen consumption (VO2peak) of the corresponding patient. Exercise testing had only marginal effects on markers of thrombin formation in patients and healthy individuals alike. In patients with CHF, exercise-induced changes in fibrinopeptide A, an index of fibrin formation, paralleled those observed in controls after submaximal exercise whereas most pronounced changes occurred in healthy subjects after maximal exercise. Plasmin-antiplasmin complexes increased almost three-fold with maximal exercise in both groups, thus indicating a marked formation of plasmin. Maximal physical exercise does not induce an exaggerated formation of thrombin and fibrin in CHF patients. The fibrinolytic response to exercise in terms of plasmin formation is not compromised in patients with dilated cardiomyopathy.

Metabolic Modulation of Inflammation-Induced Activation of Coagulation

The bidirectional interaction between coagulation and inflammation, which is relevant in various disease states that are dominated by systemic inflammatory responses, such as severe infection or chronic vascular disease, is modulated by metabolic factors. Changes in lipoprotein metabolism affect the inflammation-induced activation of coagulation, which may have impact on downstream effects, including organ dysfunction and survival. Likewise, glucose and insulin seem to influence inflammation-induced effects on coagulation and fibrinolysis. Hyperglycemia affects inflammation-induced and tissue factor-driven activation of coagulation, whereas hyperinsulinemia modulates the fibrinolytic response. There are indications that this modulatory role of metabolic factors in inflammation and coagulation may also have an impact on clinical outcome in various disease states.

Fibrinolytic Activation During Long-term Support With the Heartmate II Left Ventricular Assist Device

Human physiologic responses to pulsatile left ventricular assist devices (LVADs) are well understood; responses to the newer continuous flow pumps are not. Therefore, we evaluated the long-term effects of continuous flow LVAD support on fibrinolytic activation. Twelve recipients of an axial flow LVAD as destination therapy were assessed for fibrinolytic activation at 1, 3, 6, 9, and 12 months postimplantation. The fibrinolytic response and changes were assessed in terms of fibrinogen, D-dimer, plasma free hemoglobin, international normalized ratio (INR), and red blood cell (RBC) sedimentation rate. Bleeding and thromboembolic events were recorded. All fibrinolytic response parameters were elevated at baseline; mean RBC sedimentation rate was 51.8 mm/h, mean D-dimer was 3.95 nmol/L, and the mean fibrinogen was 356 mg/dl. The D-dimer and fibrinogen levels increased after LVAD implantation but returned to near-normal levels by 12 months. Red blood cell sedimentation rates increased indicating ongoing inflammation. Plasma free hemoglobin values decreased and remained low, an indicator of low shear rates and hemolysis. Three nonfatal bleeding events but no thromboembolic events were observed. Fibrinolytic responses initially increase after LVAD implantation but then gradually normalize.

Inhibitors and activation markers of the haemostatic system during hormone therapy: A comparative study of oral estradiol (2 mg)/ dydrogesterone and estradiol (2 mg)/ trimegestone

Epidemiological studies have shown that hormone therapy (HT) increases the risk of venous thromboembolism in post menopausal women. The mechanism of this increased risk is unknown; however, activation of the haemostatic system is known to contribute to the pathogenesis of venous thromboembolism. In post-menopausal women the estrogen/progestogen composition of the HT can influence the level of haemostatic activation. It was the objective of this study to compare changes in inhibitors and activation markers of the haemostatic system in healthy post-menopausal women taking estradiol (2 mg) combined with dydrogesterone or a new progestin, trimegestone. A multicentre study of 186 women randomised to six months therapy with either estradiol (2 mg) +trimegestone (0.5 mg) or estradiol (2 mg) +dydrogesterone (10 mg) was performed. Antithrombin and protein S activity was decreased and activated protein C (APC) resistance, D-dimer and prothrombin fragment 1.2, were increased in both groups on treatment. Protein C activity was decreased and plasmin-antiplasmin complex was increased in the trimegestone group only. The increase in plasmin-antiplasmin complex and D-dimer was greater after six cycles of treatment in the trimegestone group compared with the dydrogesterone group. In conclusion, decreased levels of inhibitors of blood coagulation and increased thrombin production were found in both groups however a greater increase in the levels of plasmin-antiplasmin complex and D-dimer was found in the trimegestone group. This suggests an enhanced fibrinolytic response in this group. Further studies are required to determine the significance of this finding with respect to venous thrombosis risk.

Time- and dose-related regional fluxes of tissue-type plasminogen activator in anesthetized endotoxemic pigs

Acute endotoxinemia elicits an early fibrinolytic response. This study analyzes the effects of the dose and duration of endotoxin infusion on arterial levels of tissue-type plasminogen activator (tPA) and pulmonary, mesenteric and hepatic plasma tPA fluxes. Pigs were randomized to receive an acute, high-dose (for 6 h, n=13, high ETX) or a prolonged, low-dose (for 18 h, n=18, low ETX) infusion of endotoxin or saline vehicle alone (for 18 h, n=14, control). All animals were fluid resuscitated to maintain a normodynamic circulation. Systemic and regional blood flows were measured and arterial, pulmonary arterial, portal and hepatic venous blood samples were analyzed to calculate regional net fluxes of tPA. Plasma tumor necrosis factor (TNF-alpha) levels were analyzed. Mesenteric tPA release and hepatic uptake increased maximally at 1.5 h in ETX groups related to dose. Maximal mesenteric tPA release [high ETX 612 (138-1185) microg/min/kg, low ETX 72 (32-94) microg/min/kg, median+/-interquartile range] and hepatic tPA uptake [high ETX -1549 (-1134 to -2194) microg/min/kg, low ETX -153 (-105 to -307) microg/min/kg] correlated to TNF-alpha levels. Regional tPA fluxes returned to baseline levels at 6 h in both ETX groups and also remained low during sustained low ETX. No changes were observed in control animals. Endotoxemia induces an early increase in mesenteric tPA release and hepatic tPA uptake related to the severity of endotoxemia. The time patterns of changes in mesenteric and hepatic tPA fluxes are similar in acute high-dose endotoxemia and sustained low-dose endotoxemia.

Heating of carbon dioxide during insufflation alters the peritoneal fibrinolytic response to laparoscopic surgery

Laparoscopic surgery is evolving rapidly. It involves the creation of a pneumoperitoneum, mostly using carbon dioxide. Cooling of the peritoneum, due to insufflation, might traumatize the peritoneum and disturb peritoneal fibrinolysis, important in peritoneal healing processes. The current study was performed to elucidate the effects of the temperature of insufflation gas on the peritoneal fibrinolytic response to laparoscopic surgery. Thirty patients scheduled for laparoscopic cholecystectomy were randomized in two groups: one group in which the pneumoperitoneum was created with carbon dioxide at room temperature, and one wherein carbon dioxide at body temperature was used. Peritoneal biopsies were taken at the start and at the end of surgery. Tissue concentrations of tPA antigen, tPA activity, uPA antigen, and PAI-1 antigen were measured using ELISA techniques. Peritoneal PAI-1 antigen levels were significantly higher at the end of the procedure in patients operated with carbon dioxide at room temperature (p < .05). A slight, but not significant, decrease in tPA antigen and activity was observed in both groups during the procedure. Peritoneal concentrations of uPa antigen did not change during the procedure. The temperature of carbon dioxide used for insufflation of the abdominal cavity affects peritoneal biology. Cooling of the peritoneum by unheated carbon dioxide causes increased peritoneal PAI-1 levels, important in peritoneal healing processes.

Fibrinolysis in patients with an abdominal aortic aneurysm with special emphasis on rupture and shock.

A ruptured abdominal aortic aneurysm (AAA) is associated with high mortality. Postoperative complications such as hemorrhage, multiple organ failure, myocardial infarction, and thromboembolism are common. An active and balanced hemostatic system is essential to avoid bleeding as well as thrombosis. When these activities are not properly regulated the patient is at risk of developing either excessive bleeding or thrombosis-related complications. Previous studies have shown a state of activated coagulation in patients with ruptured AAA. However, there are conflicting results regarding the fibrinolytic response. The aim of the present study was to investigate the fibrinolytic state pre-operatively in patients with ruptured and non-ruptured AAA in relation to the clinical outcome with special regard to the influence of shock. A prospective study was performed on 95 patients who underwent surgery for a ruptured AAA with shock (n = 43), a ruptured AAA without shock (n = 12), and a non-ruptured AAA (n = 40). Forty-one controls without an aneurysm were matched to the AAA patients according to age, gender and smoking habits. Plasma levels of tissue plasminogen activator antigen (tPAag), and plasminogen activator inhibitor type-1 (PAI-1) were measured as markers of fibrinolytic activity. D-dimer, a marker of fibrin turnover, was also measured. D-dimer was significantly higher in patients with a non-ruptured AAA compared with controls without AAA. There were significantly higher levels of D-dimer, tPAag, and PAI-1 in patients operated for ruptured compared with non-ruptured AAA. tPAag was also significantly higher in ruptured AAA patients with shock compared with without shock. No deaths occurred in patients operated on for a non-ruptured AAA or ruptured AAA without shock. There were 12 deaths after repair of a ruptured AAA with shock, of which two patients died from bleeding and the remaining 10 from multiple organ failure and cardiac failure. Our results indicate a state of activated coagulation in patients with a non-ruptured AAA, the state being intensified by rupture. The present data show normal fibrinolytic activities in patients with a non-ruptured AAA, but increased systemic fibrinolysis, as demonstrated by elevated tPAag level, in patients with a ruptured AAA. The elevated PAI-1 level indicates a simultaneous inhibition of the systemic fibrinolysis. Furthermore, the hyperfibrinolytic state was reinforced by shock in this study. However, the clinical outcome, with a relatively high incidence of thrombosis-related deaths, indicate a prothrombotic state instead of a hyperfibrinolytic state as a major point of attention in patients with shock as a result of a ruptured AAA.

Fibrinolytic responses of human peritoneal fluid in laparoscopic cholecystectomy: a prospective clinical study

The reduction in peritoneal fibrinolysis is believed to be the pathogenetic mechanism of adhesion formation. The general conclusion based on previous clinical and experimental studies is that laparoscopic procedures produce less adhesion formation. The association between this beneficial effect of laparoscopic cholecystectomy and peritoneal fibrinolytic changes is not clear. Therefore, the authors aimed to compare the effects of open and laparoscopic cholecystectomy on peritoneal fibrinolysis. For this purpose, fibrinolytic parameters in peritoneal fluid were investigated 24 h after laparoscopic and open cholecystectomies. In a prospective clinical study, peritoneal fluid was sampled via a drain 24 h after laparoscopic (n = 10) and open (n = 9) cholecystectomies. Activities and concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), and tPA/PAI-1 complex were determined by enzyme-linked immunosorbent assay (ELISA) kits. In peritoneal fluids, tPA and tPA/PAI-1 complex concentrations were higher in the open cholecystectomy group (p = 0.009 and p < 0.001, respectively), but tPA activity and PAI-1 concentrations did not differ between the groups (p = 0.514 and p = 0.716, respectively). Fibrinolytic changes in peritoneal fluid have several similarities in open and laparoscopic cholecystectomies with regard to tPA activity and PAI-1 levels. However, higher tPA levels after the open procedure probably are secondary to more intense tissue handling leading to mesothelial release of tPA.

Markedly Impaired Fibrinolytic Balance Contributes to Cardiovascular Risk in Adults with Growth Hormone Deficiency

Adults with GH deficiency (GHD) have multiple cardiovascular risk factors, including an unfavorable lipid profile and body composition as well as impairments in endothelial function and cardiac performance. We hypothesized that GHD is associated with elevated levels of plasminogen activator inhibitor-1 (PAI-1), the major inhibitor of plasminogen activation in the circulation. The objective of the study was to determine the fibrinolytic profile of adults with GHD in comparison with controls. This was a prospective, observational study including 12 adults with GHD. Twelve gender-, age-, and body mass index-matched adults served as controls. The primary outcome measures were circadian plasma PAI-1 antigen with corresponding tissue-plasminogen activator (tPA) activity values. Endothelial function was assessed by flow-mediated vasodilation and fibrinolytic potential by venous occlusion test. Adults with GHD exhibited an unfavorable 24-h fibrinolytic profile characterized by a mean 62% elevation in PAI-1 antigen (2.77 ng/ml after adjustment for baseline PAI-1; P = 0.049) in the setting of a mean 24% reduction in tPA activity (-0.17 IU/ml after adjustment for baseline tPA; P = 0.003). Fibrinolytic response was defective in GHD, as demonstrated by a sustained elevation in PAI-1 activity greater than 4 IU/ml after venous occlusion [7.2 IU/ml (interquartile range 0.8-17.4); P = 0.018]. Endothelial function was impaired in GHD, as quantified by percent flow-mediated vasodilation over 120 sec [area under the curve 3.8 (interquartile range -2.4 to 7.9) vs. 12.8 (interquartile range 2.1-19.4); P = 0.043]. Adults with GHD demonstrate alterations in plasma fibrinolytic balance, including elevated levels of PAI-1 antigen with decreased tPA activity. These changes may contribute to the increased cardiovascular morbidity within this population.

Fibrinolytic Response In Relation To Exercise Intensities Centered Around Lactate Threshold

BACKGROUND: Potential for blood coagulation increases as a function of physical exertion. This response is typically matched by an increase in fibrinolytic activity. The magnitude of fibrinolytic response has been directly associated with blood lactate concentration and may exhibit a threshold-type response similar to lactate threshold (LT). PURPOSE: To determine if there is a fibrinolytic threshold based on aerobic exercise intensity. METHODS: Eight healthy males (mean ± SD, age 24 ± 3 year, height 182 ± 9 cm, weight 83 ± 17 kg) completed a maximal cycle test and 4 submaximal cycle tests on non consecutive days. Cycling intensities for 20 minute submaximal tests were based on percentages (90%, 95%, 100%, 105%) of LT. Blood samples were obtained via clean venipuncture prior to and immediately following submaximal exercise to obtain platelet-poor plasma. tPA and PAI-1 activity were assessed using bio-functional immunosorbent assay (Biopool International, Sweden) whereas tPA antigen was analyzed using enzyme-linked immunosorbancy assay (American Diagnostica inc., Stamford, CT). Data were analyzed using repeated measures analysis of variance. RESULTS: There was no significant difference among pre-exercise values for tPA activity (90% LT = 0.37 ±0.18 IU/ml, 95% LT = 0.45 ± 0.31 IU/ml, 100% LT= 0.34 ± 0.16IU/ml, 105% LT=0.43± 0.32 IU/ml) or antigen (90% LT = 16.30 ±6.61 ng/ml, 95%LT= 13.93 ±3.00 ng/ml, 100% LT = 15.33 ± 5.56 ng/ml, 105% LT = 19.92 ± 6.94 ng/ml). Following exercise at 90% and 95% of LT, tPA activity (2.31 ± 1.23 IU/ml and 2.25 ± 1.59 IU/ml) was lower (P < 0.05) than post-exercise values for both the 100% and 105% of LT trials (2.92 ± 1.81 IU/ml and 3.13 ± 2.17 IU/ml, respectively). This effect was also true for tPA antigen, as post-exercise values for 90% and 95% of LT (20.63 ±5.95 ng/ml and 15.84 ± 7.90 ng/ml) were significantly (P < 0.05) lower than 100% and 105% LT (26.96 ± 9.92 ng/ml and 32.68 ± 7.78 ng/ml, respectively). PAI-1 did not change significantly following acute exercise for any of the trials. CONCLUSION: Our results suggest that submaximal exercise performed slightly below lactate threshold, elicits a significant fibrinolytic response. However, exercise at and even slightly above lactate threshold results in significantly higher fibrinolytic response than what is observed in the sub-threshold domain.

Fibrinolytic Responses to Resistance Training in Women

During exercise, fibrinolysis increases to protect against exertion-related ischemic events, which are often caused by an occlusive thrombus. No investigation of the fibrinolytic response to resistance training has strictly utilized female participants. This is clinically relevant due to the fact that estrogen, both endogenous and supplemental, has been shown to influence baseline fibrinolytic capacity. Furthermore, fibrinolytic potential is inversely related to body composition. It is unclear if body composition affects the fibrinolytic response to resistance exercise. PURPOSE: The purpose of this study was to assess the fibrinolytic response to resistance training in women, and to assess the effects of body composition on this response. METHODS: Fourteen healthy women (22.6 ± 4 yrs) participated in the study. Subjects were separated into two subsets by body fat as assessed by DEXA: <30% (n=6) and >30% (n=8). Each subject performed 6 sets of 10 leg extension repetitions at an intensity associated with 70% of her measured 1 repetition maximum. The two primary fibrinolytic proteins, tPA and PAI-1, were assessed at baseline, immediately after, and one hour after exercise. Results were analyzed using repeated measures ANOVA. All post-exercise values were corrected for changes in plasma volume. RESULTS: Plasma concentrations of active tPA increased significantly following exercise (p<0.05) and returned to baseline after one hour. Plasma PAI-1 activity did not change following the exercise bout (P<0.05). There was a significant group effect for PAI-1 with the >30% group exhibiting significantly higher plasma concentrations of PAI-1 than the <30% group at all three time points (p<0.05). There were no significant group × time interactions. CONCLUSIONS: Fibrinolytic potential in women increases significantly following a bout of resistance training due to an increase in tPA activity. This cardioprotective response appears to be unrelated to body composition.

Premature compared with late onset of coronary artery disease: young patients show a severe defect in fibrinolytic response to venous occlusion

Inflammatory processes play a role in the onset of acute cardiovascular events associated with activation of the coagulation system whereas the fibrinolytic system may prevent local thrombus formation. We compared 25 patients with premature coronary artery disease (CAD) (first ST-elevation myocardial infarction, < 55 years old) with 25 sex-matched patients older than 55 years at their first myocardial infarction. Six months after the acute event, patients with late onset of CAD showed a significantly higher increase of tissue-type plasminogen activator activity during venous occlusion compared with patients with premature CAD (P < 0.005). Prothrombin fragment 1+2 was higher in patients with late-onset CAD (P < 0.05), whereas the inflammatory markers C-reactive protein and soluble intercellular cell adhesion molecule-1 were not different in both groups. A multivariate analysis including cardiovascular risk factors showed that the tissue-type plasminogen activator response to venous occlusion was independently associated with patient age at onset of first ST-elevation myocardial infarction. Although in our series high age was associated with a prothrombotic state, a high fibrinolytic capacity might have some beneficial effect and contribute to a delayed onset of adverse cardiovascular events in these patients.

Quantification of the effects of thrombin activatable fibrinolysis inhibitor and α2-antiplasmin on fibrinolysis in normal human plasma

Two major proteins that inhibit fibrinolysis include thrombin activatable fibrinolysis inhibitor (TAFI) and alpha2-antiplasmin. Our goal was to quantify the contribution of TAFI and alpha2-antiplasmin to antifibrinolytic defenses with thrombelastography. Plasma activated with tissue factor/kaolin was subjected to fibrinolysis with tissue-type plasminogen activator (100 U/ml). Prior to activation, TAFI activity was inhibited with either potato carboxypeptidase inhibitor (25 microg/ml) or an anti-TAFI antibody, and alpha2-antiplasmin activity was inhibited with an anti-alpha2-antiplasmin antibody. Data were collected for 30 min, with the time of onset and rate of fibrinolysis determined. Compared with uninhibited samples, TAFI inhibition significantly (P < 0.05) decreased the time of onset of fibrinolysis by 70% and increased the rate of lysis by 70%. There was no difference between potato carboxypeptidase inhibitor and anti-TAFI antibody inhibition. Inhibition of alpha2-antiplasmin resulted in a significantly (P < 0.05) decreased time of onset (85%) and increased the rate of lysis (557%) compared with uninhibited samples. Inhibition of alpha2-antiplasmin activity resulted in a significantly (P < 0.05) greater fibrinolytic response than TAFI inhibition. In conclusion, utilization of standard inhibitors and thrombelastography permitted quantification of the effects of TAFI and alpha2-antiplasmin on fibrinolysis in plasma. Future investigation of diseases involving hypofibrinolysis (e.g. left ventricular assist devices) could be conducted using this assay system.

Peritoneal Fibrinolytic Response to Various Aspects of Laparoscopic Surgery: A Randomized Trial

Peritoneal fibrinolysis is important in peritoneal wound healing processes and adhesion formation. The peritoneal fibrinolytic response to laparoscopy is merely unknown. In the present study we investigate the effect of short-term laparoscopy on the peritoneal fibrinolytic response and the influence of intra-abdominal pressure, light intensity and choice of dissection device on this response. There were 50 patients scheduled for laparoscopic cholecystectomy randomized in five groups operated with various pressures, light intensities, and dissection devices. Peritoneal biopsies were taken at the beginning and the end of the procedure. Tissue concentrations of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1), and the tPA-activity were measured using ELISA techniques. There were no differences in tPA antigen, tPA-activity, uPA antigen, or PAI-1 antigen concentrations in biopsies taken at the beginning compared to samples taken at the end of the operation. Different intra-abdominal pressures, light intensities and the choice dissection device did not affect any of the measured parameters. Short-term laparoscopy does not affect the peritoneal fibrinolytic activity. The used intra-abdominal pressure, light intensity and choice of dissection device do not affect peritoneal activity during short-term laparoscopy.

Urban air pollution increases plasma fibrinogen and plasminogen activator inhibitor-1 levels in susceptible patients

The cardiovascular effects on fibrinolytic activity by urban air pollution are still unknown. Paired fasting blood samples during high and low air pollution days in Taipei were taken from a panel of 49 patients with coronary heart disease or multiple risk factors to study their fibrinolytic and inflammatory response to urban air pollution. Paired t-tests and mixed-effects models were used to determine the air pollution effects. Patients' plasma plasminogen activator inhibitor-1 levels were significantly increased when hourly concentrations of particulate matter with diameters less than 10 microm (PM10) were greater than 100 microg/m during the period 0800 to 1800 h. Urban air pollution has an adverse effect on plasma fibrinolytic function in a susceptible population.

Fibrinolytic response to exercise in women using third-generation oral contraceptives

The use of oral contraceptives (OC) is associated with an increased risk of thrombosis, suggesting OC exert procoagulant and/or antifibrinolytic effects. Given that physical exercise physiologically leads to an activation of blood coagulation and fibrinolysis, this study tested the hypothesis that OC might compromise the fibrinolytic response to exercise. Fibrinolytic variables were measured in 10 women (24 +/- 2 years) using OC (a formulation containing 30 micro g ethinylestradiol and 150 micro g desogestrel) and in 11 women without OC (mean +/- SD, 27 +/- 3 years) before, during and after a 1-h run on a treadmill at a velocity corresponding to an oxygen demand of 75-80% of maximum (anaerobic threshold). Exercise testing gave rise to considerable increases of tissue-type plasminogen activator antigen by seven-fold to eight-fold in women taking and not taking OC alike. In the presence of unchanged plasma levels of plasminogen activator inhibitor-1, exercise-induced release of tissue-type plasminogen activator led to enhanced plasmin formation with respect to plasmin-antiplasmin complexes, rising by (mean +/- standard error) 701 +/- 77 ng/ml (P < 0.001) in women using OC and by 695 +/- 117 ng/ml (P < 0.001 versus baseline; NS versus OC users) in controls. The fibrinolytic response to intensive physical exercise is preserved in women using OC and is similar to women not using OC.

Genetic Markers of Fibrinolytic Responses of Older Persons to Exercise Training

We assessed the interactive effect of genetic polymorphisms and exercise training on fibrinolysis in 50 - 75 yr old men (n = 17) and women (n = 28). Subjects had tissue plasminogen activator (t-PA) antigen levels and activity and plasminogen activator inhibitor-1 (PAI-1) activity measured before and after 6 mo of endurance-exercise training. Subject's DNA was typed for the PAI-1 4 G/5 G and t-PA I/D variants. Baseline PAI-1 activity, t-PA activity, and t-PA antigen levels were not different among PAI-1 or t-PA genotype groups. Overall, exercise training did not change PAI-1 activity (- 0.43 +/- 0.81 IU/mL, p = NS), increased t-PA activity (0.37 +/- 0.16 IU/mL, p = 0.02), and decreased t-PA antigen levels (- 0.88 +/- 0.20 ng/mL, p < 0.001). Although the differences in changes with training were not significant among genotype groups, significant t-PA antigen level improvements were evident only in PAI-1 4 G allele carriers and significant t-PA activity increases only in PAI-1 4 G homozygotes. t-PA genotype affected the training-induced t-PA antigen level improvements (p = 0.033) after covarying for gender and baseline t-PA antigen levels, with the smallest and largest reductions in the D homozygotes and I/D heterozygotes, respectively. These findings could have important treatment implications for the use of exercise training to reduce CV disease and thrombotic risk in older men and women.

Hemostatic response to acute physical exercise in healthy adolescents

The chronic and immediate post-exercise responses in the hemostatic and fibrinolytic systems have been shown to be variable and reflect differing adaptations with ageing and responses to exercise protocols. This study investigated the effects of acute and exhaustive exercise on the amplitude and duration of hemostatic and fibrinolytic responses in young adolescent males. The sample comprised 10 sedentary boys (13.2+/-0.5 years, 55.8+/-11.3kg, 165.7+/-7.4cm), who had not exercised or received any medication for at least 2 weeks before the experiments. The subjects performed exhaustive stepping exercise, consisting of 1s up and down cycles to fatigue. When the subjects were unable to maintain the required stepping rhythm, they were given a 30s recovery period. Following each 30s recovery participants recommenced the stepping cadence until fatigue prevented them continuing. Venous blood samples were drawn before and immediately, 1 and 24h after exercise to assess the following coagulation and fibrinolytic parameters: Platelet counts, activated partial thromboplastin time (aPTT), prothrombin time (PT), coagulation factor VIII (FVIII:C), von Willebrand factor (vWF), fibrinogen concentration, thrombin-antithrombin complex (TAT), D-dimer, plasminogen activator inhibitor (PAI-1), and tissue-type plasminogen activator (t-PA). Immediately following exercise, platelet counts, aPTT, FVIII, vWF and t-PA were significantly elevated in contrast to PAI-1, which decreased significantly until 1h after exercise. FVIII and platelet counts were elevated at 1 and 24h after exercise, respectively. Only the parameters FVIII and PAI-1 did not return to baseline values during the first hour after physical exercise. When compared to adults the results revealed different rates and ranges of coagulation and fibrinolysis parameters being activated by exhaustive exercise in this group of adolescents.