Impaired Fibrinolytic Activity Research Articles

Seven-year clinical follow-up after lumbar disc surgery: results and predictors of outcome

This study evaluates the 7-year outcome of lumbar disc surgery and the predictive value of pre- and perioperative risk factors.The 7-year follow-up rate of a sample of 122 patients was 93% ( n =114). Six per cent of the patients had undergone repeat surgery. Approximately 90% reported that they were satisfied with having undergone surgery. The clinical outcome was evaluated in 96 patients (54 men and 42 women) by means of patient-scores (VAS) of low back and leg pain, and a Clinical Overall Score (COS). In multivariate regression analyses, women were shown to have poorer outcome than men. Preoperative psychological distress and impaired fibrinolytic activity were predictors of poor 7-year outcome. Age, weight, smoking habits and physical fitness had no statistically significant prognostic value.Whether the patients were operated for one or two herniated discs, or whether surgery involved a full or partial laminectomy, did not influence the outcome significantly.

Influence of glycation on LDL-induced generation of fibrinolytic regulators in vascular endothelial cells.

Hyperglycemia and dyslipidemia are two biochemical markers of diabetes mellitus. Increased incidence of cardiovascular disease and impaired fibrinolytic activity have been found in diabetic subjects. Previous studies have demonstrated that low density lipoproteins (LDLs) stimulate the production of plasminogen activator inhibitor-1 (PAI-1) and reduce the generation of tissue plasminogen activator (tPA) in vascular endothelial cells (ECs). The present study investigated the effect of glycated LDL on the production of PAI-1 and tPA in cultured human umbilical vein ECs (HUVECs). Glycation increased the abundance of glucitollysine and conjugated dienes in LDL and amplified the overproduction of PAI-1 and the reduction in tPA generation from HUVECs induced by LDL. The steady-state levels of PAI-1 mRNA in glycated LDL-treated ECs were significantly higher than those in native LDL-treated cells. Actinomycin D blocked the increase in PAI-1 generation induced by glycated LDL. Glycated LDL did not significantly reduce the levels of tPA mRNA but attenuated de novo synthesis of tPA in ECs. Treatment with 25 mmol/L aminoguanidine, an antioxidant and inhibitor of the formation of advanced glycation end products, during glycation normalized glycated LDL-induced generation of PAI-1 and tPA in ECs. The results of the present study indicate that glycation enhances the production of PAI-1 and attenuates tPA synthesis in ECs induced by LDL, which may contribute to the increased incidence of cardiovascular complications in diabetes. Formation of advanced glycation end products or peroxidation may be involved in glycated LDL-induced alterations in the generation of fibrinolytic regulators from ECs.

Upregulation of urokinase in alveolar macrophages and lung tissue in response to silica particles.

Impaired fibrinolytic activity and persistent fibrin deposits in lung tissue have been associated with lung fibrotic disorders. The present study examined the sources of plaminogen activator (PA) changes induced by a single intratracheal administration of silica particles (5 mg) in the mouse lung. We found in both control and silica-treated animals that amiloride almost totally abolished PA activity in bronchoalveolar lavage (BAL) fluid (BALF), indicating that initial upregulation (from day 1) as well as sustained PA activity (up to day 30) observed in response to silica is related to changes in urokinase-type PA (uPA). The upregulation of BALF uPA activity was associated with a marked and persistent increase in uPA mRNA levels in lung tissue. Changes in uPA expression were also reflected in the BAL cell fraction. A maximal and constant increase in cell uPA activity was associated with the early response to silica, whereas significant but lower upregulation was still noted at the fibrotic stage. From days 3 to 30, a progressive increase in uPA mRNA levels was noted in BAL inflammatory cells elicited by silica. Because the number of BAL neutrophils was strongly correlated with BALF and BAL cell-associated uPA activity, their involvement in uPA upregulation was addressed by inducing neutropenia with cyclophosphamide (200 mg/kg ip) before administration of the silica. Neutrophilic depletion did not, however, reduce, and even increased, the BAL cell-associated uPA activity. At the BALF level, neutropenia did not change PA activity in silica-treated mice, pointing to alveolar macrophages as the principal source of uPA in response to silica. Immunohistochemical stainings identified alveolar macrophages and pneumocytes as uPA-expressing cells in silica-treated animals (day 30). Intense and heterogenous staining was observed in silicotic nodules. These findings indicate that urokinase produced by alveolar macrophages is operative not only at the alveolitis stage but also later in the fibrotic process, produced by silica particles, supporting the role of uPA in fibrogenesis.

Progressive intermittent claudication is associated with impaired fibrinolysis

Purpose: Acute complications of atherosclerosis such as stroke and myocardial infarction are caused by thrombosis and may be associated with impaired fibrinolytic activity. The current study was performed to determine whether peripheral arterial disease (PAD) and its progression are also associated with impaired fibrinolysis, by measurement of tissue plasminogen activator (tPA, the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1). Methods: The study group consisted of 80 men with a mean age of 69 years. This included 18 patients with mild intermittent claudication (MC, pain-free walking distance ≥200 meters) and 51 patients with severe claudication (SC, walking distance <200 meters). Eleven age- and sex-matched patients without PAD served as controls. All patients had measurements of serum tPA antigen using an enzyme-linked immunoadsorbent assay. Serum levels of tPA and PAI-1 activity were assayed with an amidolytic method. Mean ± SEM levels of the enzyme levels in patients with progressively more severe PAD were compared with normal controls. Results: Serum PAI-1 activity levels were significantly elevated in both PAD groups compared with normal controls ( p < 0.02). There were no significant differences in the PAI-1 activity levels in groups with worsening degrees of PAD. There was a significant decrease in tPA activity levels in patients with SC ( p = 0.01) relative to those with MC and the normal subjects. There was also a significant increase in tPA antigen level in the patients with SC compared with those with MC and the control subjects, as well as a significant inverse correlation between tPA antigen levels and pain-free walking time in patients with claudication ( p = 0.001). Conclusions: All patients with PAD in this study had significant reductions in endogenous fibrinolytic activity. Patients with SC had more impaired fibrinolytic activity than those with MC and the control subjects, suggesting that the progression to more severe levels of PAD may be associated with worsening endogenous fibrinolysis. (J Vasc Surg 1998;27:645-50.)

Coagulation and Fibrinolytic Profiles in Patients With Severe Pulmonary Hypertension

Although in situ thrombosis is a prominent finding in lung vessels from patients with primary and secondary pulmonary hypertension, to our knowledge, plasma coagulation factors that might contribute to a hypercoagulable state have not been fully investigated. We hypothesized that the local coagulation environment in the lung vasculature is important to progression if not initiation of pulmonary hypertension. Quasi-experimental cross-sectional design with concurrent controls. Referral clinics and inpatient services of a University Hospital and a Veterans Administration Medical Center. To investigate the role of plasma coagulation factors in severe pulmonary hypertension, we sampled plasma from patients with primary pulmonary hypertension, patients with pulmonary hypertension secondary to a discernible etiology, and normal adult control subjects. We detected abnormalities of the thrombomodulin/protein C anticoagulant system, evidenced by a decrease in soluble thrombomodulin, in patients with primary pulmonary hypertension. In the patients with primary pulmonary hypertension, we found impaired fibrinolytic activity, with a rise in the fibrinolytic inhibitor plasminogen activator 1 and elevated euglobulin lysis time. Lower fibrinolytic activity correlated with high mean pulmonary artery pressure. In contrast, in patients with secondary pulmonary hypertension, von Willebrand factor antigen and fibrinogen levels were increased, and fibrinolytic activity decreased. Different patterns of coagulation and fibrinolytic abnormalities are apparent in plasma from patients with primary and secondary pulmonary hypertension. Although we are unable to address causality with this study, we speculate that abnormalities of these coagulation mechanisms may initiate or play a role in perpetuation of pulmonary hypertension.

Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene.

Impaired fibrinolytic activity within the lung is a common manifestation of acute and chronic inflammatory lung diseases. Because the fibrinolytic system is active during repair processes that restore injured tissues to normal, reduced fibrinolytic activity may contribute to the subsequent development of pulmonary fibrosis. To examine the relationship between the fibrinolytic system and pulmonary fibrosis, lung inflammation was induced by bleomycin in transgenic mice that either overexpressed or were completely deficient in murine plasminogen activator inhibitor-1 (PAI-1). 2 wk after 0.075 U of bleomycin, the lungs of transgenic mice overexpressing PAI-1 contained significantly more hydroxyproline (118 +/- 8 micrograms) than littermate controls (70.5 +/- 8 micrograms, P < 0.005). 3 wk after administration of a higher dose of bleomycin (0.15 U), the lung hydroxyproline content of mice completely deficient in PAI-1 (49 +/- 8 micrograms) was not significantly different (P = 0.63) than that of control animals receiving saline (37 +/- 1 micrograms), while hydroxyproline content was significantly increased in heterozygote (77 +/- 12 micrograms, P = 0.06) and wild-type (124 +/- 19 micrograms, P < 0.001) littermates. These data demonstrate a direct correlation between the genetically determined level of PAI-1 expression and the extent of collagen accumulation that follows inflammatory lung injury. These results strongly support the hypothesis that alterations in fibrinolytic activity influence the extent of pulmonary fibrosis that occurs after inflammatory injury.

Beneficial effect of a moderately energy-restricted diet on fibrinolytic factors in non-obese men

Impaired fibrinolytic activity has been reported in the elderly and is thought to play a role in the etiology of cardiovascular disease, one of the leading causes of death in most Western countries. Since restriction of energy intake has been demonstrated to act beneficially on the aging process in a variety of species, we studied the effect of a 10-week moderately energy-restricted (ER) regimen (80% of habitual) on plasminogen activator inhibitor (PAl) activity, PAl-1 antigen, tissue plasminogen activator (tPA) activity, and tPA antigen in non-obese, middle-aged men. Moreover, the relationship between these fibrinolytic markers and glucose tolerance was investigated. Weight loss in the ER group (n = 16) was considerable (−7.4 ± 1.7 kg, P < .001). Subjects in the control group (n = 8) also lost some weight (−2.1 ± 1.5 kg, P < .01). Fasting glucose levels decreased in the ER group (−0.31 ± 0.48 mmol/L, P < .05), which was correlated with the extent of weight loss ( P < .01). Baseline insulin levels at 2 hours after an oral glucose load correlated with baseline PAl activity ( P < .001) and PAl-1 antigen levels ( P < .001). PAl activity decreased in the ER group (−2.94 ± 2.90 IU/mL, P < .001), particularly in subjects with a high baseline PAl activity (>9 IU/mL). Furthermore, energy restriction led to decreased PAl-1 antigen concentration ( P < .05), a nonsignificant increase in tPA activity, and a decrease in tPA antigen concentration ( P < .001). All these changes were more clear in subjects with a high baseline PAl activity: These results suggest that 10 weeks of moderate energy restriction has a profibrinolytic effect in non-obese, middle-aged men, at least in subjects with higher baseline PAl activity (>9 IU/mL). Moreover, in line with the suggestion that high PAl activity goes together with insulin resistance, a relationship between insulin concentration after a glucose load and PAl activity was found.

Plasma fibrinogen, fibrinolysis and (pro)vitamins; Is there a connection?

Objective: To investigate whether the relationship between anti-oxidant vitamins and cardiovascular disease can be mediated by influencing haemostasis or fibrinolysis. Design: Cross-sectional population study. Setting: Population screening in the northern Sweden MONICA study. Material: 102 men aged 40–49 years, randomly selected. Outcome measure: Univariate and multivariate relationships between on the one hand plasma fibrinogen, tPA activity and PAI-1 activity and on the other hand plasma levels of retinol, β-carotene, vitamin C, α- and γ-tocopherol. Results: Plasma fibrinogen levels were inversely correlated to lipid-standardized retinol; a relationship that persisted after adjustment for possible confounders. tPA activity was directly related to β-carotene and inversely to retinol (with or without lipid-standardization). In multiple regression analysis, lipid-standardized retinol was still a significant predictor of tPA activity when possible confounders and PAI-1 activity were taken into consideration. PAI-1 activity correlated to retinol and inversely to β-carotene but these (pro)vitamins were not significant predictors of PAI-1 activity when adjusted for confounders. Conclusion: High plasma retinol levels are associated with low plasma fibrinogen and impaired fibrinolytic activity. Other anti-oxidant (pro)vitamins seem not to act by influencing haemostasis or fibrinolysis.

The relationship between impaired fibrinolysis and coronary heart disease: a role for PAI-1

Several studies have evaluated the possible relationship between deficient fibrinolysis and ischaemic heart disease. Case-control and cross-sectional studies in patients with angiographically proved coronary disease have shown a significant increase of PAI-1 levels as compared with a control group. A significant increase of PAI-1 activity and antigen has also been demonstrated in patients with acute myocardial infarction (AMI) either during the acute event (3 h-3 days) or longer than one month after the acute event. It was suggested that the impairment of fibrinolytic activity in patients studied few days after the acute event is the consequence rather than the cause of AMI. Furthermore, the high PAI-1 levels would be non specific since they may reflect an acute phase reactant behaviour. It is, therefore, difficult to establish whether reduced fibrinolytic activity plays a role in the pathogenesis of AMI, although the fact that PAI-1 is still elevated months after the acute episode seems to support this hypothesis. In order to clarify this point the analysis of reports evaluating the predictive role of impaired fibrinolysis in the appearance of a first AMI episode is important, as well as in the recurrence of infarction. Two cohort studies explored the relationship between fibrinolytic activity and the incidence of cardiovascular disease and found similar baseline fibrinolytic activity among subjects dying from cardiovascular diseases and those who survived during the follow-up period. However, only global fibrinolytic activity was measured, so there is a possibility that levels of specific components of the fibrinolytic system might be predictors of AMI. Several studies have explored the fibrinolytic activity as a predictor of the recurrent AMI and various others have shown that elevated PAI-1 levels are associated with a higher incidence of recurrent infarction. The role of the fibrinolytic system in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty and the possible association between preoperative hypofibrinolysis and postoperative graft occlusion in patients undergoing coronary revascularization procedures has also been investigated. It has been known for considerable time that several of the well-established risk factors for coronary heart disease (CHD) such as obesity, smoking, hypertension and hyperlipoproteinemia are associated with decreased fibrinolytic activity. The positive relationship between serum triglycerides and PAI-1 levels in plasma is of particular interest, since it raises the possibility that hypertriglyceridemia confers predisposition to coronary thrombosis. Patients with diabetes mellitus, mainly of the non insulin-dependent type, show an increase of PAI-1 levels and a high incidence of atherosclerosis and CHD. Finally, some authors have found increased expression of PAI-1 mRNA in segments of human arteries from atherosclerotic patients compared with normal arteries. It can be concluded that high PAI-1 would induce hypofibrinolysis contributing to the fibrin deposition and subsequent atheroma plaque growth as well as to thrombus formation on atheroma plaque. The results of interventional studies on the modulation of endogenous fibrinolysis will convincingly establish the definitive role of fibrinolysis in the pathogenesis of atherosclerosis and CHD.

Reduced tissue type plasminogen activator activity of the gastroduodenal mucosa in peptic ulcer disease.

The gastroduodenal mucosa has a rich blood supply. An active fibrinolytic system is presumably required to maintain vascular patency, and impairment may result in reduced blood flow, focal tissue necrosis, and peptic ulcerogenesis. Tissue type and urokinase type plasminogen activator activity (expressed as mIU/mg protein) and plasminogen activator inhibitor type-1 antigen were assayed in homogenates of gastric and duodenal biopsy specimens taken from patients with: normal endoscopy (controls) (n = 14); active duodenal ulcer (n = 21); healed duodenal ulcer (n = 12); and active benign gastric ulcer (n = 15). In controls mean duodenal tissue type plasminogen activator activity was 4110 and urokinase type plasminogen activator activity 150; gastric tissue type plasminogen activator was 2760 and urokinase type plasminogen activator 170; plasminogen activator inhibitor type-1 was generally undetectable. At the edge of active duodenal ulcers tissue type plasminogen activator was considerably reduced, 2220 (p < 0.001) whereas urokinase type plasminogen activator was raised, 290 (p < 0.01). At the edge of active benign gastric ulcers tissue type plasminogen activator was substantially reduced, 1160 (p < 0.001) but urokinase type plasminogen activator was unchanged. At the scar of healed duodenal ulcers tissue type plasminogen activator was slightly reduced, 3290, but urokinase type plasminogen activator was increased, 308 (p < 0.05). H2 receptor antagonist treatment had little effect on tissue type or urokinase type plasminogen activator activity. Plasminogen activator inhibitor type-1 was increased at the edge of active ulcers (p < 0.05) especially when tissue type plasminogen activity was low (r = -0.61, p < 0.05). These findings are consistent with the hypothesis that impaired fibrinolytic activity may be implicated in peptic ulcerogenesis.

Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. A case-control study. The PLAT Group.

A case-control comparison within the framework of the prospective, multidisciplinary PLAT Study was performed to assess whether altered baseline fibrinolytic variables were associated with an elevated risk of ischemic thrombotic events in patients with documented coronary, cerebral, and/or peripheral atherosclerotic disease. Fibrinogen, D-dimer, tissue plasminogen activator (t-PA) antigen, and fibrinolytic activity before and after venous stasis (delta = difference between the two values), t-PA inhibitor, and lipid levels in 60 atherosclerotic patients with a thrombotic event during the first year of follow-up were compared with those in 94 atherosclerotic patients without such events, who were matched for age, sex, and diagnosis at enrollment. Events were associated with a higher release of delta t-PA antigen (P = .047), higher D-dimer (P = .024), and higher t-PA inhibitor (P = .001) levels. delta Fibrinolytic activity was correlated inversely with t-PA inhibitor (P < .01) and triglycerides (P < .05). D-Dimer was also correlated with systolic blood pressure (P < .01). Atherosclerotic patients at higher risk of thrombotic ischemic events are characterized by increased fibrin turnover and impaired fibrinolytic activity due to high t-PA inhibitor levels. This hemostatic disequilibrium may participate with conventional risk factors such as elevated triglyceride levels and systolic blood pressure in the multifactorial mechanism of ischemic sequelae in patients with preexisting vascular atherothrombotic disease.

The effect of surgical preparation and in-vitro distension on the intrinsic fibrinolytic activity of human saphenous vein

The objective of this study was to assess the effect of distension on the intrinsic fibrinolytic activity of human saphenous vein during its preparation for use as a bypass conduit prior to coronary artery surgery. Fibrinolytic activity was studied using fibrin plate techniques and Chromogenic assays for extractable tPA and uPA. Samples were obtained from patients undergoing routine coronary surgery. Fibrinolytic activity was compared in control vein (untouched) vein that had been prepared for use as a bypass conduit (surgical dissection, ligation of side branches and careful but uncontrolled manual distension) and segments of dissected vein distended in vitro to pressures of 230 or 120 mmHg. Uncontrolled distension and distension to 230 mmHg impaired fibrinolytic activity as determined by areas of lysis on fibrin plates (p < 0.05), (p < 0.005), tPA activity (p < 0.005) (p < 0.005) and uPA activity (p < 0.05), (p < 0.005). Distension to 120 mmHg had no effect on the fibrinolytic activity of human saphenous vein. Impaired fibrinolytic activity caused by uncontrolled distension of saphenous vein prior to its use as a vascular conduit may contribute to early vein graft thrombosis and can be avoided using controlled distension to < 120 mmHg.

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

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

Smoking, a cause of back trouble?

Epidemiological studies strongly imply that smoking may be a risk factor for back problems. It has been speculated that this is due to frequent coughing, unhealthy life style or osteoporosis in smokers. All of these hypotheses, however, do not accord with the experimental evidence. A new theory is therefore proposed. It suggests that smoking leads to malnutrition of the disc which in turn renders it more vulnerable to mechanical stress. Malnutrition can be brought about by carboxyhaemoglobin formation, nicotine-induced vasoconstriction, arteriosclerotic vessel wall changes, impairment of fibrinolytic activity and changes in the flow properties of blood. The evidence supporting these pathomechanisms is discussed. Future studies should test the above hypothesis experimentally.

Changes in blood coagulation, platelet function, and plasminogen-plasmin system in diabetes.

The increased risk of thromboembolism in people with diabetes mellitus is in part due to changes in the hemostatic mechanism including abnormal platelet function leading to platelet activation, increase in several coagulation factors, decrease in natural anticoagulants, and impaired fibrinolytic activity. Both microangiopathy and atherosclerosis in people with diabetes will enhance the thrombotic potential of these abnormal hemostatic changes. The recent recognition of a role of the components of the plasminogen-plasmin system in many biologic functions at the cellular level has led to studies showing that the angiopathic complications of diabetes may also be caused by impaired plasminogen activator function.

Fibrinolytic activity after vessel wall injury

The goal of this study was to assess fibrinolytic activity after vessel wall injury and to correlate changes in fibrinolytic activity with angiographic and histologic findings. Accordingly, in 18 atherosclerotic rabbits, vessel wall injury was produced by means of iliac artery balloon angioplasty (the injury group), whereas 8 atherosclerotic rabbits served as a control group. In all rabbits from the injury group, deep vessel wall injury was documented by either angiography or histologic study. Plasminogen activator inhibitor-1 activity in plasma increased significantly, from 21.79 ± 1.29 arbitrary units/ml (AU/ml) at baseline study to 32.05 ± 1.47 AU/ml at 6 h after vessel wall injury (p < 0.01), whereas activity remained unchanged throughout the 24h period in the control group. Plasma levels of tissue plasminogen activator activity were similar in both groups. Intravascular thrombus was found in five of six additional rabbits 6 h after vessel wall injury, that is, at the time of impaired fibrinolytic activity, whereas no thrombus was found in the control group (p < 0.05).It is concluded that deep vessel wall injury is associated with reduced fibrinolytic activity. In addition to other procoagulant factors, elevated plasminogen activator inhibitor-1 activity may lead to intravascular thrombosis and impaired resolution of thrombus.

Review: Impaired fibrinolytic activity is associated with postoperative but not symptomatic venous thromboembolism

Review: Impaired fibrinolytic activity is associated with postoperative but not symptomatic venous thromboembolism

Hypofibrinolysis in Patients with a History of Idiopathic Deep Vein Thrombosis and/or Pulmonary Embolism

An impaired fibrinolytic activity after a venous occlusion test is the most common abnormality associated with thomboembolic disease. To better characterize the causes of abnormal responses we have measured different fibrinolytic parameters, before and after 10 and 20 min of venous occlusion, in 77 patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism and in 38 healthy volunteers. The patients had a lower mean fibrinolytic response to venous occlusion than the controls and higher antigen levels of tissue-type plasminogen activator (t-PA:Ag) and plasminogen activator inhibitor type 1 (PAI-1:Ag). Before venous occlusion, PAI-1 levels were at a molar excess over those of t-PA in all patients and controls. After 20 min of venous occlusion, the release of t-PA from the vascular endothelium resulted in a molar excess of t-PA over PAI-1 in the majority of controls (72%) but only in a minority of patients (39%). To identify patients with fibrinolytic abnormalities, reference intervals (RI) for fibrinolytic activity, t-PA:Ag and PAI-1:Ag were established in healthy controls. None of the patients had low levels of t-PA:Ag, but 17 (22%) had elevated PAI-1:Ag levels before venous occlusion and 12 (16%) exhibited low fibrinolytic activity after 20 min of venous occlusion. Ten of these were among the 17 subjects with high PAI-1:Ag levels before venous occlusion. Thus, the measurement of PAI-1:Ag levels before venous occlusion (i.e. in samples taken without any stimulation) is a sensitive (83%) and specific (89%) assay for the detection of patients with an impaired fibrinolytic response to venous occlusion.

Hypofibrinolytic Activity after Total Joint Replacement

Tissue-type plasminogen activator (t-PA), tissue-type plasminogen activator inhibitor (t-PAI), and other factors (platelets, fibrinogen, fibrinogen degrada tion products, antithrombin-III, plasminogen, and α2-plasmin inhibitor [α2-PI]) related to the fibrinolytic system were studied in 21 patients undergoing total joint replacement. Seventeen of the 21 patients revealed an impaired fibrinolytic activity from the first to seventh postoperative day and a subsequent return to the preopera tive level by the fourteenth postoperative day. There were accompanying increases in the level of α2-PI and in the t-PAI/t-PA ratio, and there was decrease in plas minogen level. Such hypofibrinolytic states may be related to a higher incidence of postoperative thrombosis in total joint replacement patients.

Fibrinolysis after acute ischemic stroke

Stroke is a thrombotic process in at least 80% of cases. The acute phase of stroke is characterized by brisk thrombin activity and relatively depressed fibrinolytic activity. The presence of inhibitors of plasminogen activation may play a role in this impairment of fibrinolytic activity. Fibrinolytic activity rises slowly in the subacute phase after a stroke, but the contribution of specific activators and inhibitors during this time has not been delineated. These findings have important implications for the treatment of acute stroke. An important question remains as to whether all these changes are secondary to the stroke, or whether preexisting abnormalities of fibrinolysis contribute to the occurrence of a stroke. Large prospective epidemiologic studies using current techniques are necessary to determine whether fibrinolytic abnormalities are risk factors for stroke. [68] If this is so it would provide an important means of identifying patients at high risk for stroke. Further, it might eventually lead to new strategies of stroke prevention via augmentation of the fibrinolytic system.