Endogenous Fibrinolysis Research Articles

The Effect of Dietary Bacillus Natto Productive Protein on in vivo Endogenous Thrombolysis

The influence of dietary bacillus natto productive protein (BNPP) on endogenous thrombolysis was investigated in the rat. Animals were given a standard feed for 14 weeks, to which 0.2 or 1% BNPP was added. Thrombolysis was evaluated using an He-Ne laser-induced thrombosis model in mesenteric microvessels. Changes in thrombus volume, reflecting thrombolysis, decreased to 82% of the initial value in the control group. In contrast, the thrombus volume decreased to 67% in the animals fed 0.2% BNPP, and decreased to 51% in the group given 1% BNPP. The extent of thrombolysis in the 1% BNPP group was equivalent to that seen in animals treated with a bolus intravenous infusion of 0.2 mg/kg tissue plasminogen activator. The results demonstrated that the dietary administration of BNPP enhanced endogenous thrombolysis in a dose-dependent manner. Argatroban (2 mg/kg/h) enhanced endogenous fibrinolysis only in control animals, but not in the BNPP groups. The results support the suggestion that dietary supplementation with BNPP may provide a simple means to promote fibrinolysis not only in the treatment of thromboembolism but also in the prevention of venous occlusion.

Effects of angiotensin converting enzyme inhibitors on thrombotic mediators: potential clinical implications.

Angiotensin-converting enzyme inhibitors (ACE-I) were initially developed as therapeutic agents targeted for the treatment of hypertension. Since the initial application of these agents, several additional clinical indications have been identified such as coronary artery disease, stroke, congestive heart failure and prevention of diabetes-related complications. In addition to the blood pressure lowering effects, this class of agents has the ability to restore endothelial function, decrease oxidative stress and enhance endogenous fibrinolysis. Moreover, ACE-I possesses antiplatelet effects as well as antiproliferatory and antimigratory effects on smooth muscle cells. This article links the effects of ACE-I on thrombotic mediators to the potential clinical implications in the setting of coronary artery disease.

Marburg I polymorphism of factor VII--activating protease: a prominent risk predictor of carotid stenosis.

Atherothrombosis is a main pathomechanism in the evolution of vessel stenosis and is counteracted by endogenous fibrinolysis. Recently, the plasmatic serine protease "factor seven-activating protease" (FSAP) was recognized as a potent activator of prourokinase in vitro. The Marburg I polymorphism of FSAP impairs this potential and may thus facilitate arterial thrombosis. This analysis of the Bruneck Study involved 810 men and women aged 40 to 79 years. The ultrasound-based atherosclerosis progression model (5-year follow-up) permits differentiation between early atherogenesis and the advanced stenotic stages of carotid artery disease. The FSAP Marburg I polymorphism was found in 37 subjects (carriage rate 4.4%). Individuals with this genetic variant showed a prominently reduced in vitro capacity to activate prourokinase. No relation was found to exist between the Marburg I polymorphism and early atherogenesis. In contrast, it emerged as a strong and independent risk predictor of incident/progressive carotid stenosis (multivariate odds ratio [95%CI], 6.6 [1.6 to 27.7]). This finding equally applied to subjects with and without co-segregation of the Marburg II polymorphism. The risk profile of advanced atherogenesis further includes cigarette smoking, high lipoprotein(a), the factor V Leiden mutation, low antithrombin III, high fibrinogen, and diabetes. In concert with other genetic and acquired conditions known to interfere with coagulation or fibrinolysis, the Marburg I polymorphism of FSAP, which attenuates its capacity to activate prourokinase, is a significant risk predictor for the evolution and progression of carotid stenosis.

Carboxypeptidase B inhibitors reduce tissue factor-induced renal microthrombi in rats

Procarboxypeptidase B (also known as thrombin-activatable fibrinolysis inhibitor) is a recently described plasma zymogen known to be activated by thrombin in plasma. Carboxy-terminal lysine residues from partially degraded fibrin are important for the binding and activation of plasminogen, and carboxypeptidase B, an active form of procarboxypeptidase B, has been shown to inhibit fibrinolysis by eliminating these residues. The present paper investigates the effects of carboxypeptidase B inhibitors, dl-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGPA) and potato-derived carboxypeptidase inhibitor (CPI), on tissue factor (TF)-induced microthrombosis in rats. Intravenous injection of MGPA (3 mg/kg and higher) or CPI (0.3 mg/kg and higher) after microthrombi formation dramatically attenuated TF-induced glomerular fibrin deposition with an increase in plasma levels of d-dimer. These results indicate that carboxypeptidase B inhibitors can enhance endogenous fibrinolysis and reduce thrombi in the TF-induced microthrombosis model after systemic administration even after thrombi formation.

Preserved endothelial vasomotion and fibrinolytic function in patients with acute stent thrombosis or in-stent restenosis

Introduction: Acute stent thrombosis and in-stent restenosis are serious complications of percutaneous coronary intervention (PCI) and may be associated with vascular or platelet abnormalities. We aimed to assess endothelium-dependent vasomotion, endogenous fibrinolysis and platelet function in patients with acute stent thrombosis or in-stent restenosis. Materials and methods: Thirty-six subjects were enrolled into four groups: acute stent thrombosis, in-stent restenosis, uncomplicated PCI with stent implantation and healthy matched controls. Forearm blood flow was measured using bilateral venous occlusion plethysmography during intra-brachial acetylcholine, substance P and sodium nitroprusside infusion. Venous blood samples were withdrawn for estimation of plasma fibrinolytic variables and platelet aggregometry. Results: Acetylcholine, substance P and sodium nitroprusside caused dose-dependent increases in blood flow ( P<0.001) and substance P caused a dose-dependent increase in tissue-type plasminogen activator (t-PA) release ( P<0.001) in all groups. Thrombin, collagen, adenosine diphosphate (ADP) and the thromboxane A2 analogue, U46619, caused dose-dependent platelet aggregation ( P<0.001) in all groups. There were no significant between group differences in these responses except that, in keeping with aspirin therapy, collagen-induced platelet aggregation was impaired in patient groups compared with healthy controls ( P<0.01). Post-hoc analysis demonstrated a significant impairment of acute t-PA release in current smokers compared to non-smokers ( P<0.05). Conclusions: Despite previous reports suggesting impaired vascular function, endothelium-dependent vasomotion, endogenous fibrinolysis and platelet aggregation do not appear to play a major role in the pathogenesis of acute stent thrombosis or in-stent restenosis.

Activated thrombin-activatable fibrinolysis inhibitor attenuates spontaneous fibrinolysis of batroxobin-induced fibrin deposition in rat lungs.

Studies have shown that inhibition of TAFI by small peptides enhances pharmacological effects of tPA in animal models of thrombosis, suggesting that TAFI modulates the fibrinolytic system. In this study, we investigated the effect of activated human TAFI (TAFIa) on endogenous fibrinolysis in a rat model of intravascular fibrin deposition. (125)I-labeled fibrinogen was injected intravenously followed by a bolus injection of batroxobin, a thrombin-like enzyme. Batroxobin cleaved fibrinogen to form insoluble fibrin that was deposited in tissues, including the lungs. This was shown by a decrease of radioactivity in the blood as a result of consumption of (125)I-labeled fibrinogen and an elevation of radioactivity in the lungs 5 min following batrox-obin administration. Endogenous fibrinolysis was detected by a gradual increase in radioactivity in the blood and a decrease in radioactivity in the lungs at 30 min, an indication of radiolabeled fibrin degradation products (FDPs) being released into the circulation from the tissues. Intravenous administration of human TAFIa dose-dependently attenuated the later phase reduction of radioactivity in the lungs. When the dose of TAFIa was 218 micro g/kg, giving a peak plasma level of TAFIa 0.9 +/- 0.05 micro g/ml, the spontaneous fibrinolysis was completely prevented. These results provide direct evidence that an increase in circulating TAFIa impairs endogenous clot lysis in a rat model of fibrin deposition.

Effects of ageing and regular aerobic exercise on endothelial fibrinolytic capacity in humans.

The capacity of the vascular endothelium locally to release tissue-type plasminogen activator (t-PA) is critical for effective endogenous fibrinolysis. We determined the influence of ageing and regular aerobic exercise on the net release of t-PA across the human forearm in vivo using both cross-sectional and intervention approaches. First, we studied 62 healthy men aged 22-35 or 50-75 years of age who were either sedentary or endurance exercise-trained. Net endothelial release rates of t-PA were calculated as the product of the arteriovenous concentration gradient and forearm plasma flow to intra-arterial bradykinin and sodium nitroprusside. Second, we studied 10 older (60 +/- 2 years) healthy sedentary men before and after a 3 month aerobic exercise intervention. Net endothelial t-PA release was significantly blunted with age in the sedentary men. At the highest dose of bradykinin the increase in t-PA antigen release was approximately 35 % less (P < 0.05) in the older (from -1.0 +/- 0.4 to 37.8 +/- 3.8 ng (100 ml tissue)(-1) min(-1)) compared with young (from 0.1 +/- 0.6 to 56.6 +/- 9.2 ng (100 ml tissue)(-1) min(-1)) men. In contrast, the endurance-trained men did not demonstrate an age-related decline in the net release of t-PA antigen. After the exercise intervention, the capacity of the endothelium to release t-PA increased approximately 55 % (P < 0.05) to levels similar to those of the young adults and older endurance-trained men. Regulated endothelial t-PA release declines with age in sedentary men. Regular aerobic exercise may not only prevent, but could also reverse the age-related loss in endothelial fibrinolytic function.

Acute systemic inflammation enhances endothelium-dependent tissue plasminogen activator release in men

ObjectivesThe purpose of this study was to investigate in vivo the effects of acute systemic inflammation on the endogenous fibrinolytic capacity in men. BackgroundSystemic inflammation and endogenous fibrinolysis play a major role in the pathogenesis of coronary artery disease. Although previous studies have shown impaired endothelium-dependent vasomotor function, the effects of inflammation on the endothelial release of the fibrinolytic factor tissue plasminogen activator (t-PA) are unknown. MethodsIn a double-blind randomized placebo-controlled crossover trial, we administered a mild inflammatory stimulus, Salmonella typhivaccine, or saline placebo to eight healthy men on two separate occasions. Six hours after vaccination, blood flow and plasma fibrinolytic variables were measured in both arms during intrabrachial infusions of bradykinin (40 to 1,000 pmol/min), acetylcholine (5 to 20 μg/min), and sodium nitroprusside (2 to 8 μg/min). ResultsCompared with placebo, the S. typhivaccination caused a rise in white cell count (11.1 ± 0.5 ×109/l vs. 7.9 ± 0.8 ×109/l; p = 0.004) and plasma interleukin-6 concentrations (6.9 ± 1.4 pg/ml vs. 1.6 ± 0.4 pg/ml; p = 0.01) in addition to a significant augmentation of t-PA antigen (45 ± 9 ng/100 ml/min at peak dose vs. 24 ± 8 ng/100 ml/min at peak dose; p = 0.016, analysis of variance) and activity (104 ± 15 IU/100 ml/min vs. 54 ± 12 IU/100 ml/min; p = 0.006, analysis of variance) release during bradykinin infusion. Forearm blood flow increased in a dose-dependent manner after bradykinin, acetylcholine and sodium nitroprusside infusions (p < 0.001), but this was unaffected by vaccination. ConclusionsOur results showed that acute systemic inflammation augmented local forearm t-PA release in men, which suggests that acute inflammation may invoke a protective response by enhancing the acute endogenous fibrinolytic capacity in healthy men. Further studies are needed to clarify whether this response is impaired in patients with cardiovascular disease.

Elevation of ELISA D-Dimer Levels in Patients with Primary Pulmonary Hypertension

Background: Vasoconstriction, vascular wall remodeling and thrombosis are considered as possible etiologies of primary pulmonary hypertension (PPH). D-dimer, a degradation product of fibrin, has been increasingly used as a marker and prognostic factor in various diseases. Objective: To assess elevated ELISA D-dimer levels as a marker of endogenous fibrinolysis in patients with PPH. Patients and Methods: Comparison of ELISA D-dimer levels of 12 PPH patients (11 female, 1 male) aged 27–73 years (median 51 years) with those of sex- and age-matched healthy controls. Results: Eleven patients had New York Heart Association (NYHA) class III or IV symptoms, and one patient had NYHA class II symptoms. All patients with PPH were treated with anticoagulants and vasodilators: 5 patients were treated with continuous intravenous prostacyclin, 4 patients with continuous UT-15 and 2 patients with intermittent intravenous iloprost. Mean ELISA D-dimer levels ± SD were significantly higher in the PPH group than in the matched control group (473 ± 109 vs. 182 ± 103 ng/ml; mean difference: 291 ± 79, 95% CI: 240–341, p < 0.0001). Conclusion: These results suggest the possible involvement of endogenous fibrinolysis in the pathophysiology of PPH.

Association between physical activity and endogenous fibrinolysis in peripheral arterial disease: a cross-sectional study.

The purpose of this study was to determine whether daily physical activity was independently related to endogenous fibrinolysis in subjects with peripheral arterial disease (PAD). One hundred and six subjects with peripheral arterial disease (PAD) and intermittent claudication were characterized on the activity level of tissue plasminogen activator (tPA, the activator of fibrinolysis), the activity level of plasminogen activator inhibitor (PAI-1, the inhibitor of fibrinolysis), daily physical activity, ambulatory function, and demographic information. Subjects were separated into low (n = 36), moderate (n = 34), and high (n = 36) physical activity tertiles based on a 48-hour monitoring period with use of an accelerometer. The tPA activity of the low physical activity group (1.30 +/- 0.16 IU/mL) was 21% and 19% lower (p<0.05) than that of the moderate (1.65 +/- 0.18 IU/mL) and the high (1.61 +/- 0.15 IU/mL) physical activity groups, respectively. The PAI-1 activity of the low physical activity group (21.41 +/- 1.14 AU/mL) was 15% and 23% higher than that of the moderate (18.61 +/- 1.34 AU/mL) and the high (17.47 +/- 1.14 AU/mL) physical activity groups, respectively. Group differences in tPA activity and PAI-1 activity persisted after our controlling for group differences in measured and self-reported ambulatory measures. Daily physical activity is related to a more favorable endogenous fibrinolytic profile in PAD subjects with intermittent claudication. Subjects who expend fewer than 175 kcal/day in physical activities (approximately 35 minutes) are particularly susceptible to having a prothrombotic state. Subjects should be encouraged to participate in at least 35 minutes of physical activity each day to enhance fibrinolysis.

Enhanced endogenous thrombolysis induced by a specific factor Xa inhibitor, DX-9065a, evaluated in a rat arterial thrombolysis model in vivo

We have previously established an animal model to investigate mechanisms of arterial thrombolysis in vivo and have demonstrated that endogenous thrombolysis, mediated by thrombin-activatable fibrinolysis inhibitor, is enhanced by administration of specific thrombin inhibitors. The aim of the present study was to evaluate the effects of a synthetic and specific factor Xa inhibitor, DX-9065a, on endogenous fibrinolysis. Mural thrombi were formed in rat mesenteric arterioles by helium–neon laser irradiation in the presence of Evans blue. Thrombolysis was continuously monitored by video microscopy and was quantified using image analysis software. Oral and intravenous administration of DX-9065a enhanced endogenous thrombolysis in vivo. The mechanisms require additional investigation using other experimental systems, but nevertheless, the present results extended our previous findings and further suggested that the enhanced fibrinolysis might be due to depressed activity thrombin-activatable fibrinolysis inhibitor. The synthetic factor Xa inhibitor could provide the basis for a useful thrombolytic agent.

Recent advances in understanding endogenous fibrinolysis: implications for molecular-based treatment of vascular disorders.

The fate of a forming thrombus is determined through the delicate balance between the coagulation cascade, favouring clot formation, and the fibrinolytic system, favouring clot lysis. These processes occur simultaneously, and enhancement of fibrinolysis has been shown to reduce occlusive thrombus formation in animal models. This review examines the roles of the major fibrinolytic factors involved in clot lysis. The regulation of plasmin activity by plasminogen activators, alpha-2-antiplasmin, plasminogen activator inhibitor 1, and thrombin-activatable fibrinolysis inhibitor, and their effects on thrombus formation in vivo are discussed. Since alterations in fibrinolytic capacity appear to affect thrombus formation in animal models, there is considerable interest in the pharmacological manipulation of fibrinolysis.

Atherosclerosis, cigarette smoking, and endogenous fibrinolysis: is there a direct link?

Acute myocardial infarction is caused by thrombotic occlusion of a coronary artery at the site of a ruptured or eroded atheromatous plaque. The maintenance and regulation of tissue perfusion critically depend upon the integrity of endothelial function and the release of potent endothelium-derived factors, such as the fibrinolytic factor tissue plasminogen activator (tPA). Atherosclerosis and cigarette smoking are associated with dysfunction of the endothelium, and in particular, appear to impair the acute local endogenous fibrinolytic activity. This provides a potential mechanism whereby atherosclerosis and cigarette smoking can markedly influence the initiation, propagation, and resolution of the acute and chronic thrombotic complications of coronary artery disease through reductions in the capacity to release tPA acutely.

Myocardial ischemia induces coronary t-PA release in the pig.

Tissue-type plasminogen activator (t-PA) is the key factor in initiating endogenous fibrinolysis in the vascular compartment. Regulated release of t-PA from endothelial stores is rapidly induced by several humoral factors as well as coagulation activation products. The aim of the present study was to test the hypothesis that regional myocardial ischemia induces regulated release of t-PA in the coronary vasculature in vivo. Healthy anesthetized (pentobarbital) pigs (n=8) were studied before and after a 10-min left anterior descending region coronary artery occlusion (LAD). Coronary fluxes of lactate, total t-PA antigen (ELISA, detecting both complex bound and free fraction) and active t-PA (functional assay detecting biological free fraction) were determined at 1, 3, 5 and 10 min of reflow. Coronary occlusion induced myocardial lactate production in all animals. Net coronary release of total t-PA, which was 21 ng/min during control, increased rapidly during reflow with a peak after only 1 min (136 ng/min), and returned to baseline within 3 min. Net release of active t-PA mirrored the overall net release response, but fell short of statistical significance. Data indicate a local myocardial profibrinolytic response following regional ischemia, which may serve as a prompt defence against coronary thromboembolic events.

Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator and the risk of hypertension in a Chinese Han population.

Accumulating data support an association between hypertension and impaired fibrinolytic potential abnormalities in endogenous fibrinolysis. The present study examined whether there was an association between essential hypertension and either a polymorphism in the gene coding for t-PA or the plasma concentration of t-PA antigen. Chinese hypertensive subjects (n = 126) and normotensive controls (n = 102; sex- and age-matched with hypertensives) were recruited from among the outpatients of FuWai Hospital. The distributions of the II, ID, and DD genotypes of the t-PA gene in hypertensive patients (0.15, 0.49, 0.36) were similar to those in control subjects (0.11, 0.51, 0.38; p = 0.626). No significant difference in overall allele frequencies was found between the hypertension and control groups (p = 0.656). The allelic frequencies were in Hardy-Weinberg equilibrium. There was no evidence of an association between the level of t-PA antigen and risk of hypertension. Thus, in this case control study, neither the presence of the insertion allele of the Alu-repeat polymorphism of the t-PA nor the level of t-PA antigen were associated with the risk of essential hypertension.

Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients

Hyperhomocystinemia linked to B-vitamin deficiency is prevalent and associated with increased risk for stroke. While in vitro studies suggest homocysteine directly injures vascular endothelial thrombomodulin (TM), inhibits vonWillebrand factor (vWF) synthesis, and blocks tissue plasminogen activator (t-PA) receptor binding, these mechanisms and their reversibility by vitamin therapy are not established in humans. We investigated the effects of high-dose B-vitamin therapy on endogenous fibrinolysis and endothelial injury markers by randomizing 50 nonvitamin users with prior ischemic stroke to 3 months of treatment with multivitamins either containing folate (5 mg), B6 (100 mg), and B12 (1 mg), or lacking these components. Fasting before noon and post-methionine load plasma total homocysteine (tHcy), t-PA antigen levels, t-PA and plasminogen activator inhibitor (PAI) activities, total vWF antigen, and TM levels were measured before and after vitamin therapy. The primary analysis between treatment groups across time revealed no significant changes (P > .1) for any hematologic variables. However, within-groups analysis showed reductions of 23% in plasma TM (P < .005) and 27% in fasting tHcy levels (P < .0001) and a paradoxical 30% rise in vWF antigen levels (P < .05) after high-dose B-vitamin, treatment with no changes in controls. Pooled data revealed a significant and reproducible 20% to 28% decline in plasma t-PA activity after methionine load (n = 49, P < .02). Our findings demonstrate methionine load lowers plasma t-PA activity by a plasminogen activator inhibitor (PAI-1) independent mechanism that is not attenuated by 3 months of high-dose B-vitamin treatment. While not improving endogenous fibrinolysis profiles, these results provide initial evidence that B-vitamin treatment may selectively alter markers of vascular endothelial injury after stroke. Copyright © 2002 by National Stroke Association

Enhancement of Endogenous Plasminogen Activator-induced Thrombolysis by Argatroban and APC and Its Control by TAFI, Measured in An Arterial Thrombolysis Model In Vivo Using Rat Mesenteric Arterioles

Recent in vitro studies have demonstrated that thrombin inhibits fibrinolysis through thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B). We have recently shown that endogenous fibrinolysis in vivo is enhanced by activated protein C (APC) and the selective thrombin inhibitor, argatroban. The aim of the present study was to examine the role of TAFI in these fibrinolytic mechanisms in vivo using purified porcine pancreatic carboxypeptidase B (PPCPB) and a specific TAFIa inhibitor, potato tuber carboxypeptidase B inhibitor (PTCI) in a newly established arterial thrombolysis model. Non-occlusive, mural, platelet-rich thrombi were formed by helium-neon laser irradiation in rat mesenteric arterioles and thrombus size was measured by computerised image analysis. We confirmed that endogenous thrombolysis was enhanced by argatroban (2.0 mg/4 ml/kg/h) or APC (1.62 mg/ 2.31 ml/kg). PTCI (5.0 mg/2 ml/kg) also accelerated endogenous thrombolysis. PPCPB (3.5 mg/2 ml/kg) inhibited thrombolysis in the absence and presence of argatroban or APC. PTCI tended to further promote APC-induced thrombolysis but the differences did not reach statistical significance. The present findings were in keeping with the results of earlier studies and demonstrated that arterial, platelet-rich thrombi in vivo are degraded by naturally generated plasminogen activators. TAFI may play a significant role in the control of these mechanisms.

Coronary Artero-Venous Gradient of Endogenous Urokinase

Experimental data indicate that urokinase-type plasminogen activator (u-PA) contributes significantly to endogenous fibrinolysis and vascular remodeling in proportion to its local concentrations. In humans, however, it is not known whether u-PA levels vary at different sites and across specific vascular beds. We investigated possible regional and artero-venous differences in plasma u-PA concentrations in 15 patients undergoing cardiac catheterization. Three pairs of simultaneous samples were taken from: (1) the ascending aorta and coronary sinus; (2) left ventricle and right atrium; (3) femoral artery and femoral vein. Single-chain urokinase-type plasminogen activator (scu-PA) was measured by bioimmunoassay, and total u-PA antigen (including scu-Pa and two-chain urokinase-type plasminogen activator complexed with inhibitors (tcu-PA)) by enzyme-linked immunosorbent assay. Scu-PA represented, on average, 51±15% of total u-PA concentrations. Scu-PA and total u-PA levels were correlated ( r=.72, P<.0001) and did not differ significantly among the arterial or venous locations. There was a small but consistent increase in mean (±standard deviation (S.D.)) scu-PA concentrations from all arterial to all venous samples (1.5±0.6 vs. 1.6±0.5 ng/ml, P=.038) and from ascending aorta to coronary sinus (1.6±0.5 vs. 1.7±0.6 ng/ml, P=.046). Similarly, total u-PA levels increased from femoral artery to femoral vein (2.9±0.7 vs. 3.0±0.8 ng/ml, P<.001). In contrast, across the lungs, no significant concentration-gradient was seen in either scu-PA or total u-PA. The changes in total u-PA roughly followed those of scu-PA. These data identify an artero-venous gradient in human plasma u-PA across the coronary and peripheral beds, but not across the lungs, suggesting differences in u-PA kinetics according to vascular location.

Characterization of human prostate mast cells and their increase in periprostatic vein thrombosis.

Recent data suggest that mast cells (MCs) and their products are involved in the pathophysiology of thrombosis. In the present study, we analyzed the number, distribution, and phenotype of prostate MCs and periprostatic MCs in patients with unilateral periprostatic vein thrombosis (PVT) by immunohistochemical analysis and electron microscopy. MCs reacted with monoclonal antibodies to tryptase, chymase, and c-kit/CD117 and stained positively for tissue-type plasminogen activator (tPA) and urokinase receptor (uPAR/CD87) but did not express detectable urokinase (uPA) or plasminogen activator inhibitors (PAI-1, PAI-2). We found an increase in the mean +/- SEM number of MCs in PVT compared with control (PVT, 14.36 +/- 1.57 vs control, 5.23 +/- 0.57/mm2). The majority of MCs accumulated in the adventitia of thrombosed veins and showed a decrease in chymase expression. As MCs increase in number in PVT and express a profibrinolytic phenotype, we hypothesize that MC-derived molecules have a role in endogenous fibrinolysis.

Congenital alpha(2)-plasmin inhibitor deficiencies: a review.

Congenital alpha(2)-plasmin inhibitor deficiencies: a review.