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PubMed2006

Increased global fibrinolytic capacity as a clue for activated fibrinolysis in pre-eclampsia.

The aim of this study was to compare fibrinolysis in normal pregnancy and pre-eclampsia using individual markers of thrombosis and fibrinolysis with the contribution of a new parameter, global fibrinolytic capacity. Coagulation was determined with thrombin-antithrombin complex and prothrombin fragment 1+2 (F 1+2) and fibrinolysis markers. Tissue plasminogen activator, plasminogen activator inhibitor-1 and global fibrinolytic capacity were determined in 14 normal pregnancies and 29 women with pre-eclampsia. global fibrinolytic capacity was also determined in 14 age-matched healthy women. The Mann-Whitney U test and Pearson correlation test were used for statistical analysis. Thrombin-antithrombin complex, prothrombin fragment 1+2 levels, and global fibrinolytic capacity levels in pre-eclamptic women were significantly higher than in women with normal pregnancies (P < 0.05). Tissue plasminogen activator, plasminogen activator inhibitor-1 levels were also significantly higher in the pre-eclampsia group (P < 0.001 and P < 0.05 respectively). No significant correlation was found between global fibrinolytic capacity and thrombin-antithrombin complex, prothrombin fragment 1+2 levels, tissue plasminogen activator or plasminogen activator inhibitor-1 activity. Our results suggest that both thrombin formation and fibrinolysis are increased in pre-eclampsia compared with normal pregnancy. The increased global fibrinolytic capacity indicates that fibrinolysis remains preserved in pre-eclampsia. We suggest that global fibrinolytic capacity may be a useful parameter for accurately measuring in-vivo fibrinolysis globally, instead of with single parameters which may overlook the complex interactions between coagulation and fibrinolytic systems.

Adult↗

PubMed1991

Enhanced coagulation-fibrinolysis in patients on regular hemodialysis treatment.

Thirty-three patients with chronic uremia on regular hemodialysis treatment (RDT) have been studied to determine whether coagulation and fibrinolysis are enhanced or not. We examined predialysis values of coagulation and fibrinolysis parameters including alpha-2-plasmin inhibitor-plasmin complex (alpha 2PIC), a good index of in vivo plasmin production, and cross-linked fibrin degradation products (XL-FDP), an index of fibrinolysis secondary to coagulation. Fibrinogen was significantly higher (p less than 0.001) in RDT patients than in normal controls. ATIII activity was significantly lower in RDT patients than in normal controls (p less than 0.001). Plasminogen activity and alpha-2-plasmin inhibitor (alpha 2PI) activity were significantly lower (p less than 0.001) in RDT patients than in normal controls. Alpha 2PIC and XL-FDP were both significantly higher (p less than 0.001) in RDT patients than in normal controls. XL-FDP was inversely correlated with alpha 2PI (r = -0.486, p less than 0.01) and positively correlated with alpha 2PIC (r = 0.646, p less than 0.001). These results suggest that coagulation and fibrinolysis are enhanced in RDT patients and that the enhanced fibrinolysis is mainly due to fibrinolysis secondary to coagulation.

Adult↗

PubMed2005

Coagulation and fibrinolysis in human acute lung injury--new therapeutic targets?

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common, life-threatening causes of acute respiratory failure that arise from a variety of local and systemic insults. The need for new specific therapies has led a number of investigators to examine the role of altered coagulation and fibrinolysis in the pathogenesis of ALI/ARDS. This review summarizes our current understanding of coagulation and fibrinolysis in human ALI/ARDS with an emphasis on pathways that could be potential therapeutic targets including the tissue factor pathway, the protein C pathway and modulation of fibrinolysis via plasminogen activator inhibitor-1. The available data suggest that clinical ALI and ARDS are characterized by profound alterations in both systemic and intra-alveolar coagulation and fibrinolysis. Fibrin deposition in the airspaces and lung microvasculature likely results from both activation of the coagulation cascade and impaired fibrinolysis, triggered by inflammation. Modulation of fibrin deposition in the lung through targeting activation and modulation of coagulation as well as fibrinolysis may be an important therapeutic target in clinical ALI/ARDS that deserves further exploration.

Blood Coagulation↗

PubMed2002

Dyslipidemias and fibrinolysis.

BACKGROUND: The relation between fibrinolysis and cardiovascular disease is an open debate. Fibrinolysis is related to endothelial function and presents many molecular links with platelet and coagulation activity. Furthermore, reduced fibrinolysis has been reported in several dysmetabolic conditions. METHODS: To detect mechanisms linking dyslipidemias and fibrinolysis we evaluated 75 subjects (42 males, 33 females, 20 hypercholesterolemic, 20 hypertriglyceridemic or 20 with mixed hyperlipoproteinemia, 15 with isolated low HDL-cholesterol). Plasminogen activator inhibitor (PAI)-1, tissue-type plasminogen activator activity and plasmin-antiplasmin complexes (PAP) were determined at baseline and after the venous occlusion test. We also measured D-dimer, lipid pattern, soluble E-selectin, platelet surface P-selectin, prothrombin fragments 1 + 2 (F1 + 2), lipoprotein(a), factor VII, von Willebrand factor, plasma insulin, fibrinogen, homocysteine, thrombin activable fibrinolysis inhibitor (TAFI) activity, thrombomodulin, factor XIII, urokinase-type plasminogen activator. RESULTS: Hypertriglyceridemic patients were found to have lower PAP and D-dimer and higher PAI-1 serum levels (baseline and venous occlusion test, p < 0.001 and p < 0.01) compared to hypercholesterolemic and control subjects (p < 0.01, p < 0.001). P-selectin, F1 + 2 and TAFI were significantly increased only in hypercholesterolemic subjects (p < 0.001) and associated with reduced PAP and D-dimer, showing a linear relation with LDL-cholesterol levels (p < 0.01, r = -0.62 and p < 0.01, r = -0.59). PAI-1 activity was not different with respect to controls (baseline p = 0.59, venous occlusion test p = 0.42). Serum levels of von Willebrand factor were significantly increased in hypertriglyceridemic/low HDL subjects compared to hypercholesterolemics (p < 0.01). CONCLUSIONS: Impaired fibrinolysis in subjects with hypertriglyceridemia/low HDL-cholesterol is associated with increased serum levels of PAI-1 whereas enhanced thrombin generation and TAFI hyperactivity are the main findings in hypercholesterolemia. Such data may suggest the opportunity of evaluating several fibrinolytic factors when studied as prognostic factors in diverse dyslipidemias.

Adult↗

PubMed1992

[Differentiation of fibrinolysis and fibrinogenolysis by analysis of FDP fragments].

We previously analysed the fragments of fibrin/fibrinogen degradation products (FDP) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) combined with immunoblotting. In this report, we studied the semi-quantitative analysis of fibrinolysis (degradation of cross-linked fibrin) and fibrinogenolysis (degradation of fibrinogen and/or unstable fibrin) of patients' samples by our method. In vitro study of FDP made it clear that an appearance of D fragment confirmed fibrinogenolysis and an appearance of DD fragment and/or high molecular weight fragments which have higher molecular weight than DY or X fragment confirmed fibrinolysis. In addition, a study with mixtures of various concentrations of fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) demonstrated a dose dependent intensity of band by immunoblot method. These results show that our method is favorable for the semi-quantitative analysis of fibrinolysis and fibrinogenolysis. We applied the method to 6 samples from patients with disseminated intravascular coagulation (DIC). Consequently, fibrinogenolysis was observed in all of 6 samples, in which fibrinogenolysis was more enhanced than fibrinolysis in one sample, and an equivalent degree of fibrinolysis and fibrinogenolysis were observed in 3 of 6 samples. Although our method was probably devoid of the ability to distinguish FgDP from degradation products of unstable fibrin, these findings indicate that fibrinogenolysis is, at any rate, enhanced in the majority of patients with DIC, besides fibrinolysis.

Electrophoresis, Polyacrylamide Gel↗

PubMed1987

[Post-phlebitic leg ulcers and XYY karyotype: fibrinolysis and androgenic function tests. Apropos of 3 cases].

Three patients with karyotype XYY who had presented with deep vein thrombosis and leg ulcers (plus pulmonary embolism in two of them) were investigated for: (1) androgens (plasma testosterone measurement, testosterone oestradiol binding globulin (TeBG) assay, GnRH 50 micrograms test), and (2) haemostasis by fibrinolysis tests (euglobulin lysis time and area, antigenic plasminogen activator assay before and after 10 min venostasis). Full evaluation of haemostasis failed to demonstrate the presence of circulating anticoagulant or of antithrombin III, protein C and protein S deficiencies. One patient had neither hormonal nor fibrinolytic abnormality. The other two patients shared some clinical features with male hypogonadism (gynoid morphotype in both, hypotrophy of the testes in one, gynaecomastia in the other). They also had hormonal disorders ("over-response" to the GnRH test in one case, elevated TeGB in the other case) and abnormalities of fibrinolysis (poor response to venostasis, high baseline level of plasminogen activator). Response to venostasis became normal after 3 months of treatment with percutaneous dihydrosterone 125 mg per day in the two patients with initially poor response. The mechanism of venous pathology in XYY subjects is discussed. A genetic defect not involving the fibrinolysis system is possible since fibrinolysis was normal in one patient; however, abnormal fibrinolysis may have been responsible for the venous pathology in the other 2 patients. The role played by abnormalities of fibrinolysis in the pathogenesis of deep vein thrombosis and leg ulcers is recalled, and the possible implication of these abnormalities in patients with XYY karyotype is emphasized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Lupus nephritis with thrombosis and abnormal fibrinolysis: effect of ancrod.

Recent evidence demonstrates that coagulation plays a role in mediating glomerular damage in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis. Because of its beneficial effect in experimental glomerulonephritis, we treated patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis with ancrod, a drug known to lower fibrinogen levels and thought to activate fibrinolysis. Our patients had unusually severe renal disease; renal function was deteriorating in many. Before ancrod, vascular plasminogen activator levels were low, and levels of an inhibitor of plasminogen activation were elevated. Some patients had elevated plasmin inhibitor levels. Results were considered in two groups. In 13 patients characterized as fibrinolysis responders, the low vascular plasminogen activator and increased plasminogen activation inhibitor levels normalized. After ancrod, striking resolution of microvascular thrombosis occurred, which was associated with some improvement in renal function and blood pressure control. In five patients characterized as fibrinolysis nonresponders and who also had an elevated plasmin inhibitor (alpha 2-antiplasmin) level, normalization of fibrinolysis did not occur. There was little change in microvascular thrombosis, renal function, or blood pressure control in the fibrinolysis nonresponders. These preliminary observations demonstrate a disorder of fibrinolysis in patients with systemic lupus erythematosus with microvascular thrombi in the kidney. Ancrod therapy reverses this disorder rapidly in patients with a normal level of plasmin inhibitor and may lead to repair of glomerular damage.

Adolescent↗

PubMed1998

Thrombomodulin in human plasma contributes to inhibit fibrinolysis through acceleration of thrombin-dependent activation of plasma procarboxypeptidase B.

Thrombomodulin (TM) expressed on endothelial cells binds thrombin and initiates anticoagulant pathways. Soluble functional proteolytic fragments of TM are also present in circulating plasma. Recently, it was reported that TM accelerated thrombin-dependent plasma procarboxypeptidase B (pro-pCPB) activation in a purified system and suggested that TM may inhibit fibrinolysis in crude plasma. The aim of present study was to evaluate any functional role of soluble TM fragments in plasma or purified TM added into plasma to the regulation of coagulation and fibrinolysis. Addition of rabbit TM (1-200 ng/ml) to plasma resulted in a concentration-dependent prolongation of urokinase (UK)- or tissue plasminogen activator (t-PA)-induced clot lysis time. The concentration of TM required for the inhibition of fibrinolysis was lower than that required for the inhibition of coagulation. Addition of anti-rabbit TM IgG or anti-human TM IgG into plasma reduced UK- or t-PA-induced clot lysis time without affecting clotting times, indicating that exogenous TM or soluble TM fragments in normal human plasma participated in regulation of fibrinolysis. Moreover, the TM-dependent inhibition of fibrinolysis was observed only in the presence of thrombin and blocked by addition of carboxypeptidase B inhibitors, but not mediated by protein C activation or direct inhibition of UK, t-PA or plasmin. Analysis of various substrates and inhibitors indicated that TM accelerated thrombin-dependent pro-pCPB activation in plasma. The present results indicate that TM, including soluble TM fragments in plasma, inhibit fibrinolysis via activation of pro-pCPB in plasma.

Animals↗

PubMed2007

Prevalence and prognostic implications of non-sustained ventricular tachycardia in ST-segment elevation myocardial infarction after revascularization with either fibrinolysis or primary angioplasty.

AIMS: We compared the prevalence and prognostic implications of non-sustained ventricular tachycardia (nsVT) detected early after ST-segment elevation myocardial infarction (STEMI) in patients randomized to either fibrinolysis or primary angioplasty in the DANAMI-2 trial. METHODS AND RESULTS: Holter recordings were available in 1017 patients (fibrinolysis: n=501; primary angioplasty: n=516). Primary endpoint was all-cause mortality. The prevalence of nsVT was 8.8% in fibrinolysis-treated, and 8.1% in primary angioplasty-treated patients (P=0.71). During 4519 patient-years of follow-up (median 4.3 years), 116 patients died [fibrinolysis vs. angioplasty: HR=1.1 (95% CI, 0.8-1.6), P=0.47]. In univariate analysis, nsVT patients treated with fibrinolysis, had significantly higher mortality when compared with those without nsVT (P<0.001). However, after adjustment for other relevant prespecified risk factors, the association between nsVT and mortality did not remain statistically significant. In patients treated with primary angioplasty, nsVT was not associated with mortality in either univariate or multivariate analyses. CONCLUSION: Immediate revascularization with primary angioplasty for STEMI does not affect the subsequent prevalence of nsVT when compared with fibrinolysis. After adjustment for other relevant risk factors, the prognostic value of nsVT detected early after STEMI is limited, regardless of the chosen reperfusion strategy.

Adolescent↗

PubMed1998

Selective intra-arterial fibrinolysis of acute central retinal artery occlusion.

BACKGROUND AND PURPOSE: Occlusion of the central retinal artery (CRAO) causes a sudden decrease of monocular vision. Because early restoration of blood flow may improve outcome, we attempted to treat CRAO with selective intra-arterial fibrinolysis. METHODS: Intra-arterial fibrinolysis was performed within 6 hours after symptom onset in 17 patients with thromboembolic CRAO. Symptoms were painless, acute and severe decrease of vision. Urokinase (100 000 to 900 000 IU) was given through a microcatheter into the ophthalmic artery over 10 to 90 minutes. For comparison, the history and visual outcome of 15 control patients who did not receive fibrinolytics were evaluated. In both groups some of the patients underwent paracentesis and/or received carboanhydrase inhibitors. RESULTS: Patients who underwent fibrinolysis fared better than control patients (P=0.01). Three patients (17.6%) recovered completely after fibrinolysis and regained visual acuity of 20/20 (n=2) to 25/20 (n=1). Two additional patients (11.8%) showed a marked improvement to a visual acuity of 20/30. In 6 patients (35. 3%) vision improved slightly. They were able to count fingers, detect hand movements, or perceive light. In 6 patients (35.3%), fibrinolytic treatment was without effect. Among control patients, 1 patient (6.7%) showed partial, 4 patients (26.7%) minimal, and 10 (66.7%) no improvement of vision. CONCLUSIONS: A complete or marked improvement of visual acuity was achieved in one third of intra-arterial fibrinolysis patients but in none of the control patients. Intra-arterial fibrinolysis seems to have the potential to "lighten" the spontaneously poor outcome of CRAO.

Acute Disease↗

PubMedDate not supplied

Decision support and the appropriate use of fibrinolysis in myocardial infarction.

CONTEXT: For patients with suspected acute myocardial infarction, decisions about fibrinolytic therapy must account for trade-offs between risks and benefits, which vary according to the clinical characteristics of the patient. OBJECTIVE: To assess whether use of a decision-support computer program (DSCP) improves the selection of appropriate candidates for fibrinolytic therapy among patients with suspected acute myocardial infarction. DESIGN: Before-and-after trial at a small rural hospital in Ireland. INTERVENTION: DSCP based on a previously published decision-analysis model. With input of patient characteristics (e.g., age, sex, duration of symptoms, findings on electrocardiography) at initial evaluation, the DSCP predicts the likelihood of different outcomes (e.g., mortality, stroke) and life expectancy with and without fibrinolysis. PATIENTS: 894 consecutive patients (262 before DSCP was introduced, 632 after) admitted to the coronary care unit with suspected acute myocardial infarction between January 1993 and July 1999. OUTCOME MEASURES: Proportion of appropriate candidates (ST-segment elevation > 2 mm on electrocardiogram, symptom duration < or = 6 hours) receiving fibrinolysis before and after implementation of DSCP. RESULTS: In general, patients admitted before and after DSCP implementation had similar clinical characteristics. The preintervention group presented somewhat earlier after the onset of symptoms (5.4 hours for preintervention vs. 7.2 hours for postintervention; P < 0.01) but had fewer confirmed acute myocardial infarctions (32% vs. 38%; P = 0.13). The proportion of appropriate patients receiving fibrinolysis before and after DSCP was nearly identical (66.7% vs. 68.9%; P > 0.2). Patients who received fibrinolysis after implementation of DSCP tended to be older (66.7 years vs. 63.8 years; P = 0.11) and were more likely to be female (36% vs. 26%; P > 0.2) than those who received fibrinolysis before DSCP implementation. The door-to-needle time decreased significantly from 88 minutes to 67 minutes after implementation of DSCP (P < 0.01). CONCLUSION: Although overall rates of fibrinolysis did not change after implementation of DSCP, fibrinolytics may have been more appropriately directed toward higher risk patients who may be more likely to benefit from them.

Aged↗

PubMed1984

[Pharmacological studies of FUT-175, nafamstat mesilate. IV. Effects on coagulation, platelets and fibrinolysis].

Inhibitory effects of FUT-175 (nafamstat mesilate) on coagulation, platelets and fibrinolysis were examined. FUT-175 prolonged activated partial thromboplastin time, thrombin time and prothrombin time in rabbit plasma. FUT-175 prolonged these coagulation times in human plasma at lower concentration than in rabbit plasma. FUT-175 inhibited platelet aggregation induced by a variety of aggregation agents in rabbit platelet-rich plasma (PRP). In human PRP, FUT-175 inhibited platelet aggregation induced by a variety of aggregation agents at lower concentration than in rabbit PRP. Lipopolysaccharide induced a dose-dependent platelet aggregation in dog PRP. FUT-175 showed an inhibitory effect on this aggregation. FUT-175 inhibited clot retraction in rabbit plasma. The fibrinolysis activity was measured on fibrinolysis of rabbit plasma activated by urokinase. FUT-175 prolonged this fibrinolysis time. Inhibitory effects on coagulation and fibrinolysis were also found ex vivo. FUT-175 prolonged bleeding time in mice. These results indicate that FUT-175 has potent inhibitory effects on coagulation, platelets and fibrinolysis.

Animals↗

PubMed2001

Activation of coagulation and fibrinolysis during dengue virus infection.

Dengue virus infection can induce mild dengue fever (DF) or severe dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) in human. The pathogenesis of hemorrhage in dengue virus infection is not fully understood. Since hemostasis depends on the balance between coagulation and fibrinolysis, alternation of some coagulation parameters (platelet count and activated partial thromoboplastin time, APTT) as well as fibrinolytic parameters (tissue plasminogen activator, tPA and plasminogen activator inhibitor-1, PAI-1) were compared in 8 DHF/DSS and 17 DF patients. Patients showed thrombocytopenia, APTT prolongation, and tPA increase in the acute stage of disease, indicating activation of coagulation and fibrinolysis. The activation of coagulation and fibrinolysis in DHF/DSS patients was much more severe than DF patients. In the convalescent stage, a rise of PAI-1 level and platelet count with concomitant decline of tPA level and APTT returned to normal in both DHF/DSS and DF patients. Therefore, the activation of coagulation and fibrinolysis during the acute stage of dengue virus infection is offset by the increase of platelet and PAI-1 during convalescent stage. Taken together, these results suggest that the degree of coagulation and fibrinolysis activation induced by dengue virus infection is associated with the disease severity.

Adolescent↗

PubMed1992

Disseminated intravascular coagulation and excessive fibrinolysis in a patient with metastatic prostate cancer. Response to epsilon-aminocaproic acid.

BACKGROUND: Disseminated intravascular coagulation (DIC) and primary fibrinolysis have both been reported in association with prostate carcinoma. The correct diagnosis of the coagulopathy can be difficult and the appropriate management controversial. METHODS: A case is presented of a man in whom DIC and soft tissue hemorrhage developed after prostatic biopsy. The results of therapy and a review of the literature are discussed. RESULTS: Fibrinogen levels continued to decrease despite high-dose estrogen therapy, but they rapidly returned to normal after therapy with epsilon-aminocaproic acid. Although routine coagulation tests were suggestive of primary fibrinolysis, the results of the D-dimer assay confirmed that the patient had DIC associated with excessive fibrinolysis. CONCLUSION: A review of the literature suggests that most cases of primary fibrinolysis are probably DIC with excessive secondary fibrinolysis. In cases in which bleeding is the primary manifestation of DIC and there is a significant reduction in alpha-2-plasmin inhibitor activity, a trial of epsilon-aminocaproic acid and low-dose heparin should be considered. The failure in this case of estrogen therapy to correct the coagulopathy, despite a later good tumor response, is consistent with the delay in which anorchid testosterone levels are obtained after initiating treatment.

Adenocarcinoma↗

PubMedDate not supplied

Hyperthermic fibrinolysis with rt-PA: in vitro results.

PURPOSE: To investigate the influence of hyperthermia up to 45 degrees C on fibrinolysis with recombinant tissue-type plasminogen activator (rt-PA). METHODS: Standardized fibrin clots were incubated in a water bath for 5 hr with either rt-PA (test group) or 0.9% sodium chloride (control group) and blood plasma at temperatures of 30-45 degrees C. Concentrations of D-dimer and time to complete clot lysis were measured. RESULTS: The activity of fibrinolysis with rt-PA rose with increasing temperature: time to lysis approximately halved from 30 degrees C to 40 degrees C and the concentration of D-dimer tripled. In the control group clot size did not change. CONCLUSIONS: Activity of rt-PA-induced fibrinolysis rises distinctly with higher temperatures. Since even healthy subjects show a physiologic decline in body temperature in the extremities, in patients with occlusive arterial disease decreased activity of fibrinolysis with rt-PA can be expected. Controlled hyperthermia may improve fibrinolysis with rt-PA and should be investigated in vivo.

Fibrinolysis↗

PubMed1993

Inheritance conjointly contributing to fibrinolysis and hyperlipidemia.

Our specific aim was to assess within-family relationships of basal fibrinolytic activity and its determinants in hyperlipidemic probands (n = 34) with high lipoprotein (a) [Lp(a)] levels (> 35 mg/dL) and their first-degree relatives (n = 74) and in hyperlipidemic probands (n = 19) with Lp(a) < 35 and their first-degree relatives (n = 23). Probands' plasminogen activator inhibitor activity (PAI-Fx), the major fibrinolysis inhibitor, correlated with first-degree relatives' PAI-Fx in high-Lp(a) kindreds (r = .30, P = .06) and in Lp(a) < 35 kindreds (r = .43, P < or = .05). Probands' tissue plasminogen activator activity (tPA-Fx), the major fibrinolysis activator, was inversely associated with first-degree relatives' PAI-Fx in high-Lp(a) kindreds (r = -.30, P = .06) and in Lp(a) < 35 kindreds (r = -.49, P < or = .025). These correlations [irrespective of probands' Lp(a)] pointed to within-family heritability of the major fibrinolysis inhibitor, PAI-Fx, and the fibrinolysis stimulator, tPA-Fx. There were many other within-family correlations. High-Lp(a) probands' tPA-Fx, the stimulator of fibrinolysis, correlated with first-degree relatives' tPA-Fx (r = .32, P < or = .05). High-Lp(a) probands' plasminogen was inversely correlated with first-degree relatives' alpha 2-antiplasmin, a major fibrinolytic inhibitor (r = -.41, P < or = .01), and with their Lp(a) [r = -.24, P < or = .05]. High-Lp(a) probands' tPA-Fx correlated inversely with first-degree relatives' apolipoprotein (apo) B (r = -.28) and triglyceride ([TG] r = -.41), and positively with their high-density lipoprotein cholesterol ([HDLC] r = .40) and apo A-1 (r = .33; all P < or = .025). High-Lp(a) probands' PAI-Fx correlated positively with first-degree relatives' apo B (r = .34) and TG (r = .47), and inversely with HDLC (r = -.34) and apo A-1 (r = -.30; all P < or = .01). By stepwise regression, the Quetelet index (a measure of relative ponderosity) was independently inversely associated with tPA-Fx (P < or = .05) and positively associated with tPA-Ag and PAI-Fx (P < or = .05). TG was a positive independent determinant of PAI-Fx (P < or = .05), alpha 2-antiplasmin (P < or = .05), and plasminogen (P < or = .05). Lp(a) was a positive, independent determinant of fibrinogen (P < or = .05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1993

Effects of Poloxamer 188 on fibrin network structure, whole blood clot premeability and fibrinolysis.

The effects of Poloxamer 188 (0-5 mg/ml) on the permeability, turbidity, compaction, and fibrinolysis of fibrin network developed in human plasma, and on the permeability and fibrinolysis of network developed in whole blood were examined. Poloxamer 188 was found to increase network permeability and compaction in plasma. In networks in plasma, effects on the fibre mass-length ratio from turbidity and fibrinolysis with recombinant tissue plasminogen activator were small. Poloxamer did not alter the fibrinolysis with streptokinase. The increase in fibrin network permeability at low poloxamer concentrations was not attributable to an increase in fibre thickness, but results from alterations in the arrangement of fibrin fibres. Poloxamer also significantly increased the permeability of networks developed in whole blood. Studies with the platelet inhibitor cytochalasin B demonstrated that this effect in whole blood networks was partly from facilitation of platelet induced clot retraction. Poloxamer was not found to affect streptokinase induced fibrinolysis of whole blood networks. The effects of poloxamer support the hypothesis that depletion flocculation of fibrin intermediaries by soluble macromolecules is a significant determinant of network permeability. The therapeutic use of poloxamer will result in altered fibrin function in particular its permeability and mechanical stability. These alterations may contribute to its described antithrombotic and rheological effects.

Blood Coagulation↗

PubMed1989

Hemostasis associated with abnormalities of fibrinolysis.

Hemostatic plugs consist of platelet aggregates and fibrin mesh containing blood cells and plasma components. Hemostatic efficiency depends on the rate of formation of hemostatic plugs as well as the structural integrity and stability of the formed hemostatic plugs. Fibrin elements are major constituents contributing to the structural integrity and stability, but they are subject to fibrinolytic activity occurring spontaneously after fibrin formation. Fibrinolysis is usually suppressed by endogenous inhibitors. Increase of a profibrinolytic component or deficiency of an inhibitor would result in an accelerated fibrinolysis, causing a premature lysis of hemostatic plugs before restoration of injured vessels, leading to a hemorrhagic tendency. Such a state can be seen typically in patients with congenital deficiency of alpha 2-plasmin inhibitor or a hereditary increase of plasminogen activator, and it is also seen in acquired situations such as amyloidosis, liver cirrhosis, disseminated intravascular coagulation (particularly in patients with acute promyelocytic leukemia) and thrombolytic therapy. The hemorrhagic tendency can be well controlled by an administration of an antifibrinolytic agent: epsilon-aminocaproic acid or tranexamic acid. In contrast to an accelerated fibrinolysis causing a hemorrhagic tendency, retarded fibrinolysis may predispose an individual to a thrombotic tendency. Retarded fibrinolysis may be due to either an increase in plasminogen activator inhibitors or decrease of plasminogen activators. Quantitative or qualitative deficiency of plasminogen may also lead to a thrombotic tendency.

Antifibrinolytic Agents↗