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PubMed2002

Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study.

BACKGROUND: Although both prehospital fibrinolysis and primary angioplasty provide a clinical benefit over in-hospital fibrinolysis in acute myocardial infarction, they have not been directly compared. Our aim was to find out whether primary angioplasty was better than prehospital fibrinolysis. METHODS: We did a randomised multicentre trial of 840 patients (of 1200 planned) who presented within 6 h of acute myocardial infarction with ST-segment elevation, initially managed by mobile emergency-care units. We assigned patients to prehospital fibrinolysis (n=419) with accelerated alteplase or primary angioplasty (n=421), and transferred all to a centre with access to emergency angioplasty. Our primary endpoint was a composite of death, non-fatal reinfarction, and non-fatal disabling stroke at 30 days. Analyses were by intention to treat. FINDINGS: The median delay between onset of symptoms and treatment was 130 min in the prehospital-fibrinolysis group and 190 min (time to first balloon inflation) in the primary-angioplasty group. Rescue angioplasty was done in 26% of the patients in the fibrinolysis group. The rate of the primary endpoint was 8.2% (34 patients) in the prehospital-fibrinolysis group and 6.2% (26 patients) in the primary-angioplasty group (risk difference 1.96, 95% CI -1.53 to 5.46). 16 (3.8%) patients assigned prehospital fibrinolysis and 20 (4.8%) assigned primary angioplasty died (p=0.61). INTERPRETATION: A strategy of primary angioplasty was not better than a strategy of prehospital fibrinolysis (with transfer to an interventional facility for possible rescue angioplasty) in patients presenting with early myocardial infarction.

Aged↗

PubMed2003

Thrombin-activatable fibrinolysis inhibitor and protein C inhibitor in interstitial lung disease.

Intraalveolar activation of the coagulation system due to reduced fibrinolytic function plays a critical role in the pathogenesis of interstitial lung disease. Recently, a new potent inhibitor of fibrinolysis, thrombin-activatable fibrinolysis inhibitor, has been isolated and characterized from human plasma. This study evaluated the levels of thrombin-activatable fibrinolysis inhibitor and protein C inhibitor, another suppressor of fibrinolysis, in the bronchoalveolar lavage fluid from patients with interstitial lung disease. There were 82 patients with interstitial lung disease and 8 normal subjects. The bronchoalveolar lavage fluid levels of thrombin-activatable fibrinolysis inhibitor and protein C inhibitor were significantly higher in all patients with interstitial lung disease than in normal subjects. Both inhibitors of fibrinolysis were significantly and inversely correlated with fibrinolytic activity in all patients. The levels of thrombin-activatable fibrinolysis inhibitor were significantly correlated with those of protein C inhibitor, thrombin-antithrombin complex, and monocyte chemoattractant protein-1. Reverse transcriptase-polymerase chain reaction showed that alveolar macrophages isolated from patients with interstitial lung disease as well as immortalized lung epithelial cell lines express thrombin-activatable fibrinolysis inhibitor antigen. Overall, these findings suggest that thrombin-activatable fibrinolysis inhibitor and protein C inhibitor may play important roles in the mechanism of intraalveolar hypofibrinolysis associated with interstitial lung diseases.

Alveolitis, Extrinsic Allergic↗

PubMed1994

Cerebral intraarterial fibrinolysis at the crossroads: is a phase III trial advisable at this time?

PURPOSE: To describe the rationale for fibrinolysis, review the state of the art in cerebral fibrinolysis, and discuss whether it is time for phase III studies of cerebral intraarterial fibrinolysis. METHODS: Critical review of the literature with statistical reevaluation of significant clinical data. RESULTS: There are abundant phase III data supporting the use of thrombolysis in the cardiovascular system. However, there are no published phase III trials of intraarterial fibrinolysis in stroke. All reports of cerebral intraarterial fibrinolysis are case series. The studies are typically small with variable treatment protocols and designs that are susceptible to bias. The only analysis comparing cerebral intraarterial fibrinolysis with conventional therapy is based on nonconcurrent controls. CONCLUSIONS: Stroke is common and costly. Acute stroke intervention with fibrinolytic drugs is theoretically justified. Studies done to date have significant, inferential limitations. The data suggest an association between thrombolysis, recanalization, and prognosis. However, imprecision and inadequate control of systematic error preclude conclusions regarding clinical outcomes. Randomized, controlled trials are needed to establish the clinical value of cerebral local intraarterial fibrinolysis. However, cerebral local intraarterial fibrinolysis availability, the cerebral local intraarterial arterial fibrinolysis learning curve, anticipated technological advances, unresolved procedural controversies, and ethical and fiscal considerations make a large phase III trial impractical and ill-advised at the present time. Additional basic research is needed to set the stage for a successful clinical trial.

Cerebral Infarction↗

PubMed1994

Human renal microvascular endothelial cells as a potential target in the development of the hemolytic uremic syndrome as related to fibrinolysis factor expression, in vitro.

Renal glomerular microvascular endothelial cell damage is characteristic of Shiga toxin-associated hemolytic uremic syndrome (HUS). An impaired renal fibrinolysis may be responsible for renal microvascular fibrin accumulation during the course of HUS disease. This study examined the effect of Shiga toxin, bacterial lipopolysaccharide (LPS, endotoxin), and tumor necrosis factor (TNF) on the expression of fibrinolysis factors by human renal glomerular microvascular endothelial cells (HRMEC) in vitro. The results were compared to a previously better-characterized endothelial cell type, human umbilical vein endothelial cells (HUVEC). In HUVEC, the ratio of fibrinolysis antigens was antifibrinolytic, consisting of 55-fold more plasminogen activator inhibitor type 1 (PAI-1) than tissue-type plasminogen activator (tPA). Treatment of HUVEC with LPS or TNF accentuated this ratio by decreasing tPA and increasing PAI-1 expression. In contrast, HRMEC produced urokinase-type plasminogen activator (uPA) in a 24-fold excess to PAI-1 and were thereby profibrinolytic with regard to fibrinolysis antigen expression. LPS and TNF further decreased PAI-1 antigen expression by HRMEC. These results argue against a role for LPS or TNF in decreasing renal fibrinolysis at the level of fibrinolysis factor expression by renal endothelial cells. Nevertheless, HUVEC and HRMEC were responsive to the same LPS analogs in the same order of potency. Shiga toxin decreased fibrinolysis factor expression to a greater extent in HRMEC than in HUVEC. Since HRMEC fibrinolysis antigen expression was profibrinolytic, the Shiga toxin-mediated decrease in renal endothelial uPA synthesis may predispose renal microvasculature to thrombosis and may have implications for the development of HUS.

Bacterial Toxins↗

PubMed1989

Clinical disorders of fibrinolysis: a critical review.

Much progress has recently been made in understanding the biochemistry and physiology of endogenous fibrinolysis. As a result, a better understanding of the mechanisms and clinical consequences of disordered fibrinolysis has emerged. Increased fibrinolytic activity is an uncommon but important cause of hemorrhagic disease. Congenital disorders of fibrinolysis which cause bleeding include increased plasma plasminogen activator activity and deficiency of alpha-2 antiplasmin. Acquired disorders associated with increased fibrinolytic activity and bleeding include liver cirrhosis, amyloidosis, acute promyelocytic leukemia, some solid tumors, and certain snake envenomation syndromes. Increased fibrinolysis is important to recognize because epsilon-aminocaproic acid (EACA) may be required to prevent or control bleeding. Diminished fibrinolytic activity has been associated with a variety of thrombotic disorders, but a direct cause-and-effect relationship has yet to be established. Congenital abnormalities of fibrinolysis associated with thrombosis include plasminogen deficiency, decreased endothelial generation of plasminogen activator activity, and certain abnormal fibrinogens. Thrombosis in these disorders is effectively managed with warfarin. Diminished fibrinolysis has also been reported in "idiopathic" venous thrombosis, oral contraceptive-induced and post-operative venous thrombosis, coronary artery disease, cerebrovascular disease, systemic lupus erythematosus, and thrombotic thrombocytopenic purpura, but the significance of abnormal fibrinolysis in these disorders is uncertain. Large, prospective studies of fibrinolytic variables as risk factors for vascular and thrombotic disease are needed to determine whether pharmacologic augmentation of impaired fibrinolysis could be useful in the prevention or treatment of these disorders.

Blood Coagulation Disorders↗

PubMed2000

A simple screening assay for certain fibrinolysis parameters (FIPA).

Hemostasis, the system of generation and degradation of thrombi, consists of coagulation and fibrinolysis. Whereas global assays to study coagulation have existed for many years, there has been no simple, rapid, and economic routine test for the plasmatic fibrinolysis parameters plasminogen activator inhibitor-1, alpha2-antiplasmin, plasminogen, and aprotinin. Here a fast functional global assay for these plasmatic fibrinolytic parameters is presented. However, the present assay is not sensitive to physiological concentrations of prourokinase or tissue-type plasminogen activator. The following assay conditions have been found to be optimal: 50 microL of citrated plasma is incubated with 50 microL of 10 IU urinary-type plasminogen activator (urokinase)/mL, 1.1 mmol/L tranexamic acid, 1% polygelin, 0.1% Triton X-100, phosphate-buffered saline, pH 7.4, for 20 min at 37 degrees C (plasmin generation phase). Then 50 microL of 3 mmol/L HD-Nva-CHA-Lys-pNA, 1.05 mol/L KCl is added, and deltaA (405 nm)/10 min (37 degrees C) is determined, by using a microtiterplate reader (plasmin detection phase). The results are calibrated against pooled normal plasma (100% plasmatic fibrinolytic parameters activity). The intra- and interassay coefficients of variation have been found to be less than 5%. The detection limit (sensitivity) of the functional fibrinolysis assay is 5 % of the normal plasmatic fibrinolysis parameters activity. The normal plasmatic fibrinolysis parameters activity is 100%, sigma = 25%. The plasmatic fibrinolysis parameters activity correlates negatively (r = -0.684) with the plasminogen activator inhibitor-1 activity of patient samples. The plasmatic fibrinolysis parameters assay is a simple, rapid, and economic functional test for several clinical relevant fibrinolysis parameters.

Adolescent↗

PubMed1992

Enhancement of fibrinolysis with ultrasound energy.

The effect of ultrasound energy on fibrinolysis of artificial thrombus in vitro was investigated. Thrombi produced by the Chandler loop method were exposed to low-energy ultrasound (5,000-6,000 Pa) in an ultrasound bath (48 kHz) for 60 seconds. Fibrinolysis with urokinase was enhanced from 40.6% +/- 1.8% to 59.2% +/- 2.6% (mean +/- standard deviation) with ultrasound exposure after a 60-minute incubation. Ultrasound alone without urokinase resulted in no fibrinolysis. In a second experiment, a newly developed miniature ultrasound-emitting ceramic element (2 x 1 x 5 mm) was attached to the tip of a catheter. Ultrasound exposure (225 kHz) from this device markedly enhanced fibrinolysis with urokinase from 8.9% +/- 1.5% to 37.3% +/- 0.8% (total ultrasound exposure 60 seconds, intensity 30 mW/cm2) after a 30-minute incubation. After a 120-minute incubation, fibrinolysis with ultrasound exposure was 61.1% +/- 1.8% versus 46.7% +/- 0.5% for the unexposed group. Ultrasound enhancement of fibrinolysis was less pronounced with longer incubation time (60 or 120 minutes). Ultrasound energy enhanced fibrinolysis with urokinase, especially in the early phase of lysis. This new device may shorten the time needed to complete fibrinolysis and reduce total drug dosage needed for treatment of thromboembolic diseases.

Adult↗

PubMed1998

Enhancement of fibrinolysis with 40-kHz ultrasound.

BACKGROUND: Ultrasound at frequencies of 0.5 to 1 MHz and intensities of > or =0.5 W/cm2 accelerates enzymatic fibrinolysis in vitro and in some animal models, but unacceptable tissue heating can occur, and limited penetration would restrict application to superficial vessels. Tissue heating is less and penetration better at lower frequencies, but little information is available regarding the effect of lower-frequency ultrasound on enzymatic fibrinolysis. We therefore examined the effect of 40-kHz ultrasound on fibrinolysis, tissue penetration, and heating. METHODS AND RESULTS: 125I-fibrin-radiolabeled plasma clots in thin-walled tubes were overlaid with plasma containing tissue plasminogen activator (tPA) and exposed to ultrasound. Enzymatic fibrinolysis was measured as solubilization of radiolabel. Tissue attenuation and heating were examined in samples of porcine rib cage. Fibrinolysis was increased significantly in the presence of 40-kHz ultrasound at 0.25 W/cm2, reaching 39+/-7% and 93+/-11% at 60 minutes and 120 minutes, compared with 13+/-8% and 37+/-4% in the absence of ultrasound (P<0.0001). The acceleration of fibrinolysis increased at higher intensities. Attenuation of the ultrasound field was only 1.7+/-0.5 dB/cm through the intercostal space and 3.4+/-0.9 dB/cm through rib. Temperature increments in rib were <1 C/(W/cm2). CONCLUSIONS: These findings indicate that 40-kHz ultrasound significantly accelerates enzymatic fibrinolysis at intensities of > or =0.25 W/cm2 with excellent tissue penetration and minimal heating. Externally applied 40-kHz ultrasound at low intensities is a potentially useful therapeutic adjunct to enzymatic fibrinolysis with sufficient tissue penetration for both peripheral vascular and coronary applications.

Animals↗

PubMed1988

Impaired fibrinolysis-inducing capacity for postinjury phenotype of cultivated human arterial and human atherosclerotic intimal smooth muscle cells.

Impaired fibrinolysis is believed to promote atherosclerosis and contribute to myocardial infarction. The major triggering factor for fibrinolysis is vascular tissue plasminogen activator (t-PA), and the aim of this study was to evaluate the capacity of human arterial smooth muscle cells (SMC) for induction of fibrinolysis. SMC were plated on labeled fibrin gels, and lysis was measured as release of label. Fibrinolytic capacity was dependent on the phenotypic state of SMC. The "multilayered phenotype" to which SMC modulate after cellular injury had a much lower fibrinolysis-inducing capacity than the more ordinary "monolayered" SMC type. Fibrinolysis was mediated by activation of plasminogen. In long-term experiments under conditions imitating thrombolysis, platelet-derived growth factor promoted fibrinolysis indirectly by increase of SMC number, and a direct effect on cellular production of t-PA was not detected. SMC from atherosclerotic intima had a much lower capacity for induction of fibrinolysis than cells from adjacent nonatherosclerotic intima. SMC also displayed several structurally detectable interactions with the fibrin substratum, such as organization of the gel by means of extension of numerous filamentous processes and contraction and wrinkling of the gel. In conclusion, human arterial SMC in vitro induce fibrinolysis by activation of plasminogen. This capacity is dependent on phenotype and lowered for SMC from atherosclerotic intima, suggesting impairment after arterial injury and in atherosclerosis.

Arteries↗

PubMed1982

Significance of cross-linking of alpha 2-plasmin inhibitor to fibrin in inhibition of fibrinolysis and in hemostasis.

When blood is clotted, alpha(2)-plasmin inhibitor (alpha(2)PI) is cross-linked to fibrin by activated fibrin-stabilizing factor (activated coagulation Factor XIII, plasma transglutaminase). The amount of cross-linked alpha(2)-PI is proportional to the amount of alpha(2)PI present at the time of clotting. Plasma from a patient with congenital deficiency of alpha(2)PI was supplemented with various amounts of purified alpha(2)PI. Clots were prepared from these plasmas and were suspended in plasma containing a normal concentration of alpha(2)PI, and spontaneous clot lysis was observed. When the clot was formed in the presence of calcium ions and thereby allowing cross-linking to occur, the rate and extent of fibrinolysis were found to be inversely proportional to the concentrations of alpha(2)PI present in the clot at the time of clotting. When the clot was formed in the absence of calcium ions so that no cross-linking occurred, the clot underwent fibrinolysis at similar rates, regardless of the concentrations of alpha(2)PI in the clot. When the clot formed in the presence of calcium ions was squeezed and washed to remove unbound proteins before being suspended in plasma, the extent of fibrinolysis was also inversely proportional to the amount of alpha(2)PI cross-linked to fibrin. Similar results were obtained when the clot was suspended in buffered saline instead of plasma. These observations suggest that spontaneous fibrinolysis is mainly carried out by plasminogen/plasminogen activator bound to fibrin, and this fibrinolysis caused by fibrin-associated activation of plasminogen was mainly inhibited by alpha(2)PI cross-linked to fibrin. To further support this concept, alpha(2)PI treated with activated fibrin-stabilizing factor and that had lost most of its cross-linking capacity was used in similar experiments. This modified alpha(2)PI had the same inhibitory activity on plasmin as the native inhibitor, but gave significantly less inhibition of fibrinolysis in every experiment, particularly when the clot was compacted by platelet-mediated clot retraction or by squeezing. Thus, it was concluded that alpha(2)PI cross-linked to fibrin plays a significant role in inhibition of physiologically occurring fibrinolysis. It is further suggested that the absence of cross-linked alpha(2)PI contributes to accelerated fibrinolysis and hemorrhagic tendency in patients with congenital deficiency of fibrin-stabilizing factor.

Calcium↗

PubMed2001

Regulation of fibrinolysis in plasma by TAFI and protein C is dependent on the concentration of thrombomodulin.

Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme, that after activation down regulates fibrinolysis. TAFI is activated by thrombin in the presence of the cofactor thrombomodulin (TM). By stimulation of TAFI activation TM down regulates fibrinolysis, however TM is also a cofactor in the activation of protein C. Activated protein C (APC) can up regulate fibrinolysis by limitine the activation of TAFI via the attenuation of thrombin production. We studied these counteracting fibrinolytic properties of TM in plasma by measuring the activation of TAFI during tissue factor induced coagulation. TAFI activation was stimulated at low concentrations of TM but decreased at higher concentrations of TM. Similarly, the clot lysis times increased at low concentrations of TM but decreased at higher concentrations of TM. The reduction of TAFI activation at high TM concentrations was found to be dependent on a functional protein C pathway. The concentration of TM is therefore an important factor in the regulation of TAFI activation and in the regulation of fibrinolysis. High concentrations of TM result in up regulation of fibrinolysis, whereas low concentrations of TM have a down regulatory effect on fibrinolysis. These results suggest that fibrinolysis might be differentially regulated by TM in different parts of the body depending on the local TM concentration in the vasculature.

Blood Coagulation↗

PubMed1986

[ Fibrinolysis in diabetes mellitus].

In 198 diabetic patients of type I and type II and in 111 healthy persons of a control group the activity of fibrinolysis was investigated before and after a venous occlusion test of ten minutes. Spontaneous fibrinolysis was significantly diminished in diabetics of both types in comparison to the control group. A relationship to the degree of seriousness of retinopathy could not be identified in type I. The activity of fibrinolysis decreased in all test persons in old age. In diabetics patients of type II as well as in that age group being more than 56 years old there were smaller activities of fibrinolysis at higher stages of retinopathy. A negative linear correlation of this spontaneous activity of fibrinolysis could be found for the duration of the disease as well as for age. Different forms of diabetic therapy and the sex allowed no influence of the activity of fibrinolysis to be recognized. An increase of the activity of fibrinolysis after congestion could be established in diabetics as well as in the control group. After venous congestion the fibrinolytic activity showed no differences any longer in diabetics and in the control group, with age, duration of the disease and form of therapy being taken into consideration. Before and after venous congestion a negative linear correlation could be revealed between the activity of fibrinolysis and the height of blood sugar level. Therefore, the real blood sugar concentration should be taken into account in evaluating the fibrinolytic activity.

Adolescent↗

PubMedDate not supplied

Coagulation- and fibrinolysis-related antigens in plasma and dialysate of CAPD patients.

OBJECTIVE: The present study is aimed at gaining insight into coagulation and fibrinolysis in the peritoneal cavity of patients on continuous ambulatory peritoneal dialysis (CAPD). For this purpose we measured coagulation- and fibrinolysis-related antigens in plasma and dialysate, comparing patients with and without peritonitis. DESIGN: Markers of activated coagulation and fibrinolysis in plasma and dialysate of CAPD patients were determined at different time points (0 hr, 2 hr, 4 hr) after infusion of the dialysis solution in the peritoneal cavity. Prothrombin fragment (F1 + 2), thrombin-antithrombin III complex (TAT), and fibrin monomer (FM) were chosen as parameters of activated coagulation. Fibrin degradation products (FbDP), D-dimer (DD), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) were measured as parameters for ongoing fibrinolysis. Beta 2-microglobulin, albumin, and IgG were used as marker proteins for the diffusion of proteins of intravascular origin into the peritoneal cavity. PATIENTS: Eleven clinically stable CAPD patients, who had not suffered from peritonitis during the last six months, and 5 CAPD patients with an acute episode of bacterial peritonitis were studied. RESULTS: In the dialysate of stable CAPD patients (n = 11) the concentration of activation markers of coagulation and fibrinolysis increased continuously with dwell time. After four hours we found remarkably high levels of the coagulation markers F1 + 2 (0.4 +/- 0.1 nmol/L), TAT (6.5 +/- 1.0 ng/mL), and FM (24.5 +/- 7.1 micrograms/mL), and the fibrinolysis markers DD (851 +/- 26 ng/mL), FbDP (1.0 +/- 0.3 microgram/mL), t-PA (3.3 +/- 0.8 ng/mL), and PAI-1 (2.6 +/- 1.2 ng/mL). The dialysate-to-plasma (D/P) ratios of all of these antigens were significantly higher compared to the D/P ratios of proteins with similar molecular weight, which are not produced intraperitoneally (beta 2-microglobulin, albumin, and IgG). These findings point to a local, thrombin-induced intraperitoneal fibrin generation during regular CAPD. Compared with clinically stable CAPD patients, the patients with bacterial peritonitis (n = 5) had significantly higher levels of F1 + 2 (5.3 +/- 1.6 nmol/L), TAT (57.8 +/- 10.7 ng/mL), FM (972 +/- 3.2 micrograms/L), FbDP (16.4 +/- 2.9 micrograms/L), and PAI-1 (7.3 +/- 2.4 ng/mL) in the dialysate (4-hr dwell time), and a 2.4-times higher ratio between FM and FbDP. These results can be interpreted as an intraperitoneal imbalance between coagulation and fibrinolysis during peritonitis. CONCLUSION: Our study demonstrates a high intraperitoneal fibrin formation, not only during peritonitis but also in clinically stable CAPD patients. The remarkably high levels of coagulation (F1 + 2, TAT, FM) and fibrinolysis (FbDP, DD, t-PA, PAI-1) related antigens in the dialysate of patients without peritonitis cannot be explained by transport from plasma into the peritoneal cavity and may reflect a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin is obviously disturbed in CAPD patients with peritonitis, who had significantly higher levels of coagulation markers in the dialysate and a higher ratio between FM and FbDP.

Acute Disease↗

PubMed1990

PTCA following myocardial infarction: use of bailout fibrinolysis to improve results.

The results of percutaneous transluminal coronary angioplasty (PTCA) in 307 lesions in 235 patients within 60 days of myocardial infarction (MI) were compared with the PTCA results in 591 lesions in 489 patients without recent MI, and the effect of fibrinolysis to treat recurring occlusive clot during angioplasty was studied. In 210 lesions in patients with MI who did not receive fibrinolysis during the MI (group A), 58 lesions were categorized as primary failures; bailout fibrinolysis brought the final failure incidence to 42 lesions (20%). In 97 lesions in patients with MI who received fibrinolysis during the acute MI (group B), 22 lesions were categorized as primary failures; bailout fibrinolysis resulted in final failures of 16 lesions (16.5%). In 591 lesions in patients without a recent MI (group C), there were 85 primary failures and 81 final failures after bailout fibrinolysis. Analysis of the PTCA results in each group with respect to whether the lesions were totally or partially occluded showed that more of the lesions attempted in the groups with MI (groups A and B) were totally occluded (TO) and that with use of bailout fibrinolysis the success rate of PTCA in TO lesions was the same in all groups. Similarly, with use of fibinolytic bailout during PTCA the success rate in partially occlusive lesions was not different between the groups. We conclude that bailout thrombolysis during PTCA is usually effective, especially in those who have recently had an MI, and that with availability of bailout fibrinolysis, PTCA in those with recent MI is not any less sucessful than in those without recent MI.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

PubMed2006

Percutaneous coronary intervention after fibrinolysis: a multiple meta-analyses approach according to the type of strategy.

OBJECTIVES: We performed a meta-analysis of randomized trials that enrolled ST-segment elevation myocardial infarction patients treated with fibrinolysis to assess the potential benefits of: 1) rescue percutaneous coronary intervention (PCI) versus no PCI; 2) systematic and early (< or =24 h) PCI versus delayed or ischemia-guided PCI; 3) fibrinolysis-facilitated PCI versus primary PCI alone. BACKGROUND: The impact of PCI strategies after fibrinolysis on mortality or reinfarction remains to be established. METHODS: The meta-analysis was performed using the odds ratio (OR) as the parameter of efficacy with a random effect model. Fifteen randomized trials (5,253 patients) were selected. The primary end point was mortality or the combined end point of death or reinfarction. RESULTS: Rescue PCI for failed fibrinolysis reduced mortality (6.9% vs. 10.7%) (OR, 0.63; 95% confidence interval [CI], 0.39 to 0.99; p = 0.055) and the rate of death or reinfarction (10.8% vs. 16.8%) (OR, 0.60; 95% CI, 0.41 to 0.89; p = 0.012) compared with a conservative approach. Systematic and early PCI performed during the "stent era" led to a nonsignificant reduction in mortality compared with delayed or ischemia-guided PCI (3.8% vs. 6.7%) (OR, 0.56; 95% CI, 0.29 to 1.05; p = 0.07) and to a 2-fold reduction in the rate of death or reinfarction (7.5% vs. 13.2%) (OR, 0.53; 95% CI, 0.33 to 0.83; p = 0.0067). This benefit contrasted with a nonsignificant increase in the rate of both mortality (5.5% vs. 3.9%, p = 0.33) or death or reinfarction (9.6% vs. 5.7%, p = 0.06) observed in the "balloon era." Fibrinolysis-facilitated PCI was associated with more reinfarction as compared with primary PCI alone (5.0% vs. 3.0%) (OR, 1.68; 95% CI, 1.12 to 2.51; p = 0.013) without significant impact on mortality (OR, 1.30; 95% CI, 0.92 to 1.83; p = 0.13). CONCLUSIONS: Our findings support rescue PCI and systematic and early PCI after fibrinolysis. However, the current data do not support fibrinolysis-facilitated PCI in lieu of primary PCI alone.

Angioplasty, Balloon, Coronary↗

PubMed2004

Exercise training enhances endogenous fibrinolysis in peripheral arterial disease.

PURPOSE: Acute clinical events resulting from atherosclerosis (myocardial infarction, stroke) are associated with impaired endogenous fibrinolysis, the system by which the body lyses inappropriately formed thrombus. Endurance exercise training improves fibrinolysis in normal subjects and those with coronary artery disease. The hypothesis of this study was that exercise training would improve fibrinolysis in subjects with peripheral arterial disease (PAD). METHODS AND RESULTS: Twenty-one men with intermittent claudication (IC-EX) underwent treadmill exercise training for 6 months. Twenty age-matched male subjects with IC were followed for the same period (IC-NONEX). Fibrinolytic activity was measured prior to entry into exercise or "usual care," and at the completion of the study period. Fibrinolysis was quantified by measurement of the activity levels of tissue plasminogen activator (tPA, the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1), using an amidolytic method. Fibrinolysis, quantified as increased PAI-1 activity, was reduced in both claudicant groups relative to healthy controls at baseline. After 6 months of exercise, subjects in the IC-EX group experienced significant improvements in fibrinolytic activity, manifested as a 23% decrease in PAI-1 activity and a 28% increase in tPA activity. No changes occurred in the IC-NONEX group. In the IC-EX group, subjects with the highest initial PAI-1 values experienced the greatest decreases in PAI-1 activity and thus the greatest benefit from exercise. CONCLUSIONS: Patients with PAD have impaired fibrinolytic activity, manifested primarily as increases in the inhibitor of fibrinolysis, PAI-1. Six months of exercise training reduced these impairments, and may serve as an intervention to reduce cardiovascular mortality and morbidity in these patients.

Aged↗

PubMed1987

Physiologic regulation and pathologic disorders of fibrinolysis.

Physiologic fibrinolysis is a reparative process that occurs in response to hemostatic plug or thrombus formation. The final enzymatic step, fibrin proteolysis, results from a coordinated interaction of enzymes and inhibitors, which produces effective action at the site of the disease and spares the proteins of the blood or uninvolved parts of the vascular system. The agent of fibrinolysis, the enzyme plasmin, is derived from its zymogen (plasminogen) through limited proteolysis effected by plasminogen activators. They can be grouped according to functional and immunologic properties into the tissue type and urokinase-like plasminogen activators. The ability of alpha 2 antiplasmin to neutralize efficiently free (nonfibrin-bound) plasmin prevents inappropriate systemic activation of fibrinolysis. This control is superseded in certain conditions, such as with the therapeutic administration of plasminogen activators to lyse pathologic thrombi, when plasmin degrades plasma fibrinogen into degradation fragments (X, Y, D, and E). Degradation of cross-linked fibrin results in distinctive products that are characterized by cross-linked (factor XIIIa-induced) derivatives such as D dimer. Disease states resulting from abnormalities in the fibrinolytic system include both hemorrhagic disorders, resulting from excessive fibrinolysis, and thrombosis, as the result of deficient fibrinolysis. Hyperfibrinolysis can result from pharmacologic administration of activators or from defective inhibition produced by alpha 2 antiplasmin deficiency. Hypofibrinolytic thrombosis can result from hereditary defects, for instance of plasminogen or fibrinogen, or from pharmacologic inhibition of fibrinolysis such as with epsilon aminocaproic acid. Laboratory evaluation of fibrinolysis is useful for monitoring fibrinolytic therapy and assessing thrombotic disorders and bleeding; it also includes the specific measurements of plasminogen activator, plasminogen, plasmin, inhibitors and circulating fibrinogen, and cross-linked fibrin degradation products.

Fibrin Fibrinogen Degradation Products↗

PubMed1998

Fibrinolysis in pediatric patients undergoing cardiopulmonary bypass.

OBJECTIVE: Thromboelastographic evaluation of the influence of fibrinolysis on blood loss and blood product transfusions in children during cardiac surgery. DESIGN: Prospective study. SETTING: University-affiliated, pediatric medical center. PARTICIPANTS: Two hundred seventy-eight consecutive children undergoing cardiac surgery. INTERVENTIONS: Blood sampling for coagulation tests, including native and protamine-modified thromboelastography. MEASUREMENTS AND MAIN RESULTS: Blood coagulation tests were measured before, during, and after cardiopulmonary bypass (CPB). Demographic data, perioperative blood loss, and blood product transfusions were prospectively recorded. Fibrinolysis was defined as thromboelastography of A30/MA less than 0.85 (MA, maximum amplitude; A30, amplitude 30 minutes after MA) and was noted in 3% of children pre-CPB, 16% during CPB, and 3% post-CPB. Fibrinolysis before CPB was associated with poor cardiac output. Fibrinolysis during CPB occurred in young children (aged 350 +/- 836 days) undergoing complex surgery with prolonged CPB (119 +/- 48.8 minutes) and deep hypothermia (25.6 degrees C +/- 4.7 degrees C). These patients received blood products after CPB and were not fibrinolytic after transfusion. They incurred similar blood loss (in mL/kg) and received similar volumes of blood products (mL/kg) as age-matched and surgery-matched patients without fibrinolysis. CONCLUSION: A group of children at risk for fibrinolysis during CPB was identified. However, fibrinolysis during CPB did not influence blood loss or the total volume of blood products transfused.

Blood Loss, Surgical↗