Plasminogen Activity Research Articles

Plasminogen and plasmin activity in patients with coronary artery disease.

While coronary artery disease (CAD) is associated with disturbances of the plasma fibrinolytic system, the nature of these disturbances is not fully defined. Fibrinolysis is regulated by plasmin, whose production is mediated by plasminogen activator conversion of plasminogen (Plg) to plasmin. The cascade is modulated by feedback loops that include Plg activator inhibitor 1 (PAI-1). Molecular interactions with Plg kringle domains play an important role in regulating plasmin production and its modulation of fibrinolysis. We hypothesized that interactions of tissue plasminogen activator (tPA) with Plg kringle domains regulates plasmin levels in patients with stable CAD. Plasma was collected from patients (n = 33) with an angiographically significant CAD and controls (n = 18) with angiographically established normal or minimally diseased arteries. Plasmin activity, tPA activity, and plasma levels of Plg, PAI-1, uPA, and tPA were determined. CAD patients had 1.7-fold greater plasmin activity (P = 0.02) that correlated with 1.5-fold higher tPA activity when compared to controls. Epitope mapping of Plg domains showed Plg differences in epitope exposure between the two groups. Plasma from CAD patients had 50% less (P < 0.001) detectable kringle 4 and 48% less (P = 0.007) detectable kringles 1-3. Based on detectable differences in Plg, we conclude that in patients with stable CAD, Plg complexed with tPA exists in a conformation that enables increased tPA activity and Plg conversion to plasmin.

Effects of incubation temperature and salt concentration on plasminogen activators in cheese curd

Abstract Plasmin (PL) can play a major role in the proteolysis of dairy products, especially during cheese ripening. The effects of cook temperature and salt concentration on PL in cheese systems have been studied; however, the effects of cheese making conditions on plasminogen activators (PAs) have not. Therefore, the objective of this study was to determine the effect of curd cook temperature and salt concentration on PL, plasminogen (PG), and PAs. PL, PG, and urokinase-type PA activities extracted from cheese curds cooked at 21 °C were significantly ( P ⩽ 0.05 ) lower than those extracted from cheese curds cooked at 37 or 55 °C. Activity assays showed that PG was the only component in the PL enzyme system that was significantly affected by salt concentration, with higher PG-derived activity at 0% NaCl than 5% NaCl. Specialized electrophoresis confirmed that PL and PA activities increased with increasing cook temperature, and, unlike the activity assays, indicated that increase in salt concentration (to a certain extent) could increase PL and tissue-type PA activities.

Acute sensorineural hearing loss and vertigo in a young adult with congenital plasminogen disorder

A 19-year-old Japanese man exhibiting acute right sensorineural hearing loss and vertigo was referred to the Jichi Medical School Hospital in June 1994. Although he had no history of recurrent thrombosis and no family history of thrombosis, he had undergone reconstruction of a right foot joint fracture 4 months earlier. Screening studies for plasminogen activity demonstrated 10% of normal plasminogen activity and his plasminogen was diagnosed as “plasminogen Tochigi” by the gene analysis using restriction enzyme Fnu4HI. The patient's hearing returned to normal with administration of heparin, and he was prescribed warfarin for the prevention of thrombosis until October 1995. There was no recurrence of hearing loss during seven years of follow-up. The cause of this patient's hearing loss is believed to be associated with consumption of the already low levels of plasminogen as a result of his surgery as well as congenital plasminogen disorder.

An investigation of the plasmin–plasminogen system in caprine milk and cheese

Abstract The variability in activities of plasmin (PL) and plasminogen (PG) in bulk milk samples from different breeds of goats was investigated. The mean PL activity was higher (19.56±4.72 U g −1 ) than in milk from other ruminant species, while PG-derived activity was, surprisingly, lower (12.84±5.31 U g −1 ). No significant differences in PL and PG levels were observed among goat breeds, but PL activity and PL/PG ratio increased in late lactation compared with early lactation. PL activities in pilot-scale curds (acid or rennet) and in some Italian cheeses made from caprine milk were also measured. Generally, acid curds and cheeses had lower residual PL and PG-derived activities than rennet curds and semi-hard cheeses. In addition, the PL/PG ratio was greatly reduced in rennet curds, due to a higher extent of PG-derived activity. Measurement of proteolysis of β -casein in curds confirmed that more extensive proteolysis occurred in rennet curds, which had higher residual PL activities.

Influence of Calcium and Phosphorus, Lactose, and Salt-to-Moisture Ratio on Cheddar Cheese Quality: Proteolysis During Ripening

Proteolysis in cheese is influenced by the state of proteins (protein–calcium–phosphate interactions), level of indigenous milk enzymes (plasmin), externally added milk-clotting enzymes (chymosin), and endogenous and exogenous enzymes from starter and non-starter lactic acid bacteria (NSLAB). The objective of this study was to determine how different levels of calcium (Ca) and phosphorus (P), residual lactose, and salt-to-moisture ratio (S/M) in cheese influence proteolysis during ripening. Eight cheeses with 2 levels of Ca and P (0.67 and 0.47% vs. 0.53 and 0.39%, respectively), 2 levels of lactose at pressing (2.4 vs. 0.78%), and 2 levels of S/M (6.4 vs. 4.8%) were manufactured. The cheeses were analyzed for changes in pH 4.6-soluble N, and starter and NSLAB counts during 48 wk of ripening. Cheeses at d 1 were also analyzed for residual chymosin, plasmin, and plasminogen activity. A significant increase in soluble N was observed during ripening for all the treatments. Cheeses with low Ca and P, low lactose, and low S/M treatments exhibited higher levels of proteolysis as compared to their corresponding high treatments. Differences in the rate of proteolysis for cheeses with different levels of Ca and P might be due to changes in protein conformation and differences in residual chymosin in the cheeses. Cheeses with low Ca and P were manufactured by lowering the pH at set and drain, which led to higher chymosin retention in cheeses with low Ca and P compared with high Ca and P. Differences in proteolysis between treatments with different levels of lactose were also partly attributed to residual chymosin activity. In all treatments, a major fraction of plasmin existed as plasminogen, indicating minimal contribution of plasmin to proteolysis in Cheddar cheeses. The number of starter bacteria, in all treatments, decreased significantly during ripening. However, the decrease was larger in the case of high S/M treatments compared with low S/M treatments. In contrast, the number of NSLAB increased during ripening, and low S/M cheeses had higher counts compared with high S/M cheeses. The differences in proteolysis due to S/M were partially attributed to changes in protein conformation or bacterial proteolytic activity.

Matrix metalloproteinases in the process of invasion and metastasis of breast cancer

Metastatic cascade in malignant tumors, including breast cancer, starts with localized invasion of the host tissue. This process, requiring that tumor cells separate from each other, includes loss of homotypic and heterotypic cell adhesion and cell-cell contact inhibition, acquisition of motility, exacerbated by "epithelial-to-mesenchymal transition", and production of proteolytic enzymes which degrade basal membrane and extracellular matrix. In this sense, aside from urokinase type plasminogen activator, increased expression and activity of matrix metalloproteinases (MMPs) is one of the earliest and most sustained events in tumor progression, playing a role in angiogenesis, invasion and metastasis. MMPs are a family of 23 zinc metalloproteinases, secreted as latent pro-enzymes, activated by proteolytic cleavage, and inhibited by the tissue inhibitors of metalloproteinases. The most commonly connected MMPs with the processes of metastasis are MMP-2 (gelatinase A) and MMP-9 (gelatinase B), due to their ability to degrade collagen type IV, major component of vascular basement membrane. MMP-2 and MMP-9 are also required for the switch to the "angiogenic phenotype" during tumor progression and activation of dormant tumor cells. The association of the increase in serum MMP-2 and MMP-9 activity and clinical stage suggests the usefulness of these parameters as markers in the follow-up and prognosis of breast cancer patients. The concept of "stromal-directed therapy" of cancer, with MMP-inhibitors directed against MMPs as targets, is based on the observed MMP up-regulation in tumors.

A Comparison of Glass and Plastic Blood Collection Tubes for Routine and Specialized Coagulation Assays: A Comprehensive Study

Blood collection tubes made from plastic are beginning to replace glass tubes. Coagulation test results can be influenced easily by preanalytic factors, including exposure to surfaces that activate the clotting cascade. To compare the effects of the blood collection tube material on 22 coagulation assays performed in clinical laboratories. Paired blood samples from 28 healthy volunteers were drawn into BD Vacutainer Glass Citrate Tubes and BD Vacutainer Plus Plastic Citrate Tubes, and the results of coagulation assays were determined in parallel. No statistically significant differences were observed between glass and plastic for 14 assays: prothrombin time (and international normalized ratio); activated partial thromboplastin time; activated protein C resistance; antithrombin activity; factors II, V, VIII, and IX; alpha2-antiplasmin; plasminogen activity; von Willebrand factor antigen; ristocetin cofactor; thrombin time; and reptilase time. Statistically significant differences were found for fibrinogen; chromogenic protein C activity; protein S activity; PTT-LA lupus anticoagulant-sensitive activated partial thromboplastin time; and factors VII, X, XI, and XII. Mean differences ranged from 0.4% to 5.5% and were unlikely to be of clinical significance. The results of this study suggest that plastic tubes can be used in place of glass tubes for a wide variety of coagulation assays.

Fluorescent Labeling Study of Plasminogen Concentration and Location in Simulated Bovine Milk Systems

A fluorescent labeling method was developed to study plasminogen (PG) concentration and location in simulated bovine milk. Activity and stability of PG labeled with Alexa Fluor 594 (PG-594) were comparable to those of native PG. The fluorescent signal of PG-594 exhibited pH, temperature, and storage stability, and remained stable throughout typical sample treatments (stirring, heating, and ultracentrifugation). These characteristics indicate broad applicability of the fluorescent labeling technique for milk protease characterization. In an example application, PG-594 was added to simulated milk samples to study effects of heat and β-lactoglobulin (β-LG) on the distribution of PG. Before heating, about one-third of the PG-594 remained soluble in the whey fraction (supernatant) whereas the rest became associated with the casein micelle. Addition of β-LG to the system slightly shifted PG-594 distribution toward the whey fraction. Heat-induced PG-594 binding to micelles in whey-protein-free systems was evidenced by a decrease of PG-594 from 31 to 15% in the whey fraction accompanied by an increase of PG-594 from 69 to 85% in casein micelle fractions. When β-LG was present during heating, more than 95% of PG-594 became associated with the micelle. A comparison with the distribution pattern of PG-derived activities revealed that heat-induced PG binding to micelles accompanies heat-induced PG inactivation in the micelle fraction. Incubation of the casein micelles with the reducing agent β-mercaptoethanol revealed that disulfide bonds formed between PG and casein or between PG and casein-bound β-LG are the mechanisms for heat-induced PG binding to casein micelles. Western blotting and zymography results correlated well with fluorescent labeling studies and activity studies, respectively. Theoretically important findings are: 1) when heated, serum PG is capable of covalently binding to micellar casein or complexing with β-LG in whey and then coadhering to micelles, and 2) PG that associated with micellar casein through lysine binding sites before heating is capable of developing heat-induced disulfide bonds with casein. The overall results are PG covalently binding to micelles and inactivation thereafter. Our results suggest that, instead of thermal denaturation through irreversible unfolding, covalent bond formation between PG and other milk proteins is the mechanism of PG inhibition during thermal processing.

Ligneous Periodontitis and Ehlers‐Danlos Syndrome

Generalized membranous gingival enlargement due to an accumulation of fibrin deposits associated with severe alveolar bone loss (ligneous periodontitis) is a rare condition, and plasminogen deficiency seems to play a central role in its pathogenesis. However, this condition has not been described in association with syndromes. This article reports a case of ligneous periodontitis in a boy with the classic type of Ehlers-Danlos syndrome (EDS). A 12-year-old white male presented with generalized gingival overgrowth and severe alveolar bone loss. A physical examination revealed clinical signs of EDS (velvety skin with mild hyperextensibility, marked hypermobility of the limb joints, atrophic scars on his knees, and easy bruising), which is associated with a positive family history for joint hypermobility. A biopsy of gingival tissues was submitted for routine histology, hematoxylin and eosin (H&E), and direct immunofluorescence (antifibrinogen). An evaluation of plasminogen activity was also performed. Histopathology revealed chronic periodontitis with fibrinoid material deposition, and direct immunofluorescence proved to be positive for fibrin. Functional plasminogen was reduced. A conclusive diagnosis of ligneous periodontitis due to plasminogen deficiency associated with the classic type of EDS was rendered. Ehlers-Danlos syndrome can be associated with ligneous periodontitis. In the present case, the histologic examination represented an important tool in the differential diagnosis, because it ruled out EDS type VIII as the associated systemic factor to periodontal breakdown.

Role of annexin II in estrogen-induced macrophage matrix metalloproteinase-9 activity: The modulating effect of statins

Annexin II (ANXII) is a receptor for tissue plasminogen activator and plasminogen for the conversion to plasmin, which, in turn, induces metalloproteinase-9 (MMP-9). 17β-Estradiol (E 2) is reported to decrease plasminogen activity inhibitor-1 and increase plasmin and matrix metalloproteinase activity. However, the combined effects of estrogen and statins on macrophage MMP-9 activity and ANXII expression remain unclear. Treatment of J774A.1 macrophages with 1.0–100 nM of E 2 for 24 h increased both MMP-9 activity and ANXII expression in a dose-dependent manner ( p < 0.05). Preincubation with EGTA (10 mM) released ANXII from the cell membrane and inhibited the E 2-mediated MMP-9 activity as did incubation of macrophages with anti-annexin IgG. In the presence or absence of E 2 (5 nM), simvastatin treatment in the range of 0.1–5.0 μM significantly reduced macrophage MMP-9 enzymatic activity ( p < 0.005) in a dose-dependent manner. In the presence or absence of E 2, simvastatin also decreased ANXII expression ( p < 0.05). These findings indicate that ANXII plays a central role in modulating the enzymatic activity of MMP-9 in response to E 2 and that E 2-mediated ANXII expression and MMP-9 activity can be prevented by simvastatin. Prevention of E 2-mediated activation of MMP-9 by simvastatin suggests that concurrent statin use may account for early event risk of myocardial infarction seen with hormone therapy in recent clinical trials.

Endothelial function is impaired in patients with primary antiphospholipid syndrome

Introduction The aim of this study was to evaluate endothelial function in patients with primary antiphospholipid syndrome (PAPS). Patients and methods Flow mediated (FMD) and glyceryl trinitrate (GTN) induced dilation of the right brachial artery were studied in 25 patients with PAPS and 25 controls matched by age, sex and conventional risk factors for atherosclerosis. Fibrinogen, D-dimer, adhesion molecules, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigens and activities were measured. Results Mean (SD) FMD was significantly lower in PAPS than in controls (8 ± 5% vs. 15 ± 6%, P < 0.001); GTN-induced dilation did not differ between the groups. There was a correlation between the baseline diameter of the brachial artery and duration of the disease (− 0.56, P < 0.05) and between GTN induced dilation and duration of the disease (0.51, P < 0.05). Concentrations of vascular cell adhesion molecule-1 ( P < 0.001), intracellular adhesion molecule-1 ( P < 0.001) and fibrinogen ( P < 0.05) were higher in patients than in controls but no differences were observed for D-dimer, t-PA and PAI-1 antigens and activities. There was correlation between concentration of vascular cell adhesion molecule-1 and FMD (− 0.35, P < 0.05) and between intracellular adhesion molecule-1 and FMD (− 0.41, P < 0.05). Conclusions This study shows that endothelial function is impaired in patients with primary APS, possibly contributing to accelerated atherosclerosis and thromboembolic complications in these patients.

Anti-thrombic activity of Korean herbal medicine, Dae-Jo-Whan and its herbs

The anti-thrombic properties of the Korean herbal medicine, Dae-Jo-Hwan (DJW), which is consisted of 11 herbs (indicated as concentrations) of Rehmanniae radix 24%, Hominis placenta 5%, Testudinis carapax 9%, Eucommiae cortex 9%, Asparagi radix 9%, Phellodendri cortex 9%, Achyranthis radix 7%, Liriopis tuber 7%, Angelicae sinensis radix 7%, Ginseng radix 6%, and Schizandrae fructus 3%, were investigated. The extracts of DJW and its 11 herbs, except G. radix, A. sinensis radix and S. Fructus, inhibited the endotoxin-induced hepatic venous thrombosis in high cholesterol diet-treated rats. Also the extract inhibited the endotoxin-induced decrease in blood platelets and fibrinogen, and endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats. In in vitro experiments, the extract was shown to have inhibitory effect on collagen- and ADP-induced blood platelet aggregation, on thrombin-induced conversion of fibrinogen to fibrin and on the activity of plasminogen or plasmin. In conclusion, the protection of extracts of Korean herbs on the ischemic infarction induced artificially might be related to their inhibitory effects on DIC, platelet coagulation and thrombic action.

Detection of plasma coagulants and anticoagulants in patients of cerebral infarction with deep vein thrombosis and its clinical significance

目的 探讨凝血、抗凝血指标在缺血性脑卒中(CI)并发下肢深静脉血栓形成(LDVT)中的意义.方法检测了50例CI并发LDVT患者和50例健康人血管性血友病因子(vWF)、P-选择素(GMP-140)、凝血酶原片断1+2(F1+2)、总蛋白S(PS)含量及抗凝血酶(AT)、蛋白C(PC)、纤溶酶原(PLg)、纤溶酶原激活抑制物-1(PAI-1)活性.结果 CI并发LDVT患者的vWF、GMP-140、F1+2含量及PAI-1活性明显高于正常对照组;总PS含量,AT、PC、PLg活性明显低于正常对照组.结论血液的高凝状态是缺血性脑卒中并发深静脉血栓形成的主要因素。

Plasma TAFI and soluble CD40 ligand do not predict reperfusion following thrombolysis for acute myocardial infarction

Introduction Thrombolytic therapy fails to achieve reperfusion in almost a third of patients with acute myocardial infarction. Thrombin activatable fibrinolysis inhibitor (TAFI) and soluble CD40 ligand (sCD40L) are novel endogenous fibrinolytic and atherothrombotic factors that determine clot stability. We investigated whether admission plasma thrombin activatable fibrinolysis inhibitor (TAFI) and soluble CD40 ligand (sCD40L) concentrations predicted reperfusion following thrombolytic therapy in patients with acute myocardial infarction. Materials and methods Prior to administration of thrombolytic therapy, venous blood was collected from 110 patients presenting with acute ST segment elevation myocardial infarction and plasma assayed for tissue plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor type-1 antigen (PAI-1), TAFI antigen and activity, C-reactive protein (CRP) and sCD40L concentrations. Reperfusion was determined using continuous ST segment monitoring. Results Reperfusion occurred in 77 (70%) patients with a mean treatment to reperfusion time of 83 ± 46 min. Peak creatine kinase was significantly lower in patients who reperfused (1578 ± 1199 versus 2200 ± 1744 U/L; P < 0.05) and correlated with time to reperfusion ( r = 0.44 [95% CI: 0.23 – 0.61], P = 0.0001). There was a modest correlation between plasma TAFI antigen and activity ( r = 0.3 [95% CI: 0.04 – 0.53]; P < 0.05). There were no significant associations between coronary reperfusion and plasma concentrations of t-PA, PAI-1, TAFI, CRP or sCD40L. Conclusions Systemic plasma TAFI, sCD40L and CRP concentrations do not predict reperfusion in patients receiving thrombolytic therapy for acute ST elevation myocardial infarction.

July 26 Highlight and Commentary

Ovbiagele and Saver evaluated the effect of smoking on outcome following intravenous thrombolysis for acute ischemic stroke and found that recent smokers who received thrombolysis experienced better early outcomes compared to nonsmokers. see page 293 Commentary by Steven R. Levine, MD Cigarette use has been linked to progression of existing atherosclerosis, increased fibrinogen, C-reactive protein, and homocysteine1 as well as vascular endothelial dysfunction. Smoking’s effects on clotting dynamics are more complex, and may depend on patient age and presence of atherosclerosis. Tissue plasminogen activator (t-PA) antigen and activity levels, plasminogen …

Effect of levothyroxine replacement therapy on coagulation and fibrinolysis in severe hypothyroidism

We previously demonstrated that patients suffering from moderate hypothyroidism were at increased risk of thrombosis contrasting with the bleeding tendency of those presenting severe hypothyroidism. The latter state is associated with hemostatic anomalies including von Willebrand type 1 disease and increased fibrinolytic capacity. With the exception of von Willebrand type 1 disease, reversibility of hemostatic changes is not established after levothyroxine replacement therapy. Therefore our objective was to analyze the reversibility of these anomalies. We analyzed the impact of levothyroxine treatment on lipid parameters, fibrinogen, platelet count, D-dimers, alpha2 antiplasmin activity, plasminogen activity, tissue plasminogen activator antigen (t-PA Ag), plasminogen activator inhibitor type 1 antigen (PAI-1 Ag) and coagulation factors (factor VIII coagulant, von Willebrand factor antigen, von Willebrand factor and factor IX) in 23 patients with severe hypothyroidism (TSH level > 50 mU/ I). Mean fibrinogen levels increased by 14.2% while t-PA Ag and PAI-1 Ag increased by 42.6 and 69%, respectively, after correction of hypothyroidism. Interestingly, post-treatment PAI-1 Ag levels tended to be higher in patients with normal-high final TSH levels than in patients with normal-low final TSH levels. Our results suggest that normalization of fibrinolysis is obtained after a transient decrease of fibrinolytic activity. We also confirmed the correction of coagulation factor abnormalities upon levothyroxine replacement therapy. We demonstrated that the coagulation disorders and the hyperfibrinolytic status of severe hypothyroid patients were corrected upon levothyroxine therapy. However, the clinical consequences of the transient decrease of the fibrinolytic activity during the course of TSH normalization need further studies.

Association between platelet activation and fibrinolysis in acute stroke patients

We aimed to evaluate platelet activation and fibrinolyis in acute atherosclerotic ischemic stroke patients to clarify the relationship between them. Plasma P-selectin antigen, tissue plasminogen activator (tPA) antigen and activity, and plasminogen activator inhibitor-1 (PAI-1) activity were determined in 60 acute atherosclerotic stroke patients and matched control subjects. All patients were examined within 72 h after stroke onset. The levels of P-selectin, tPA antigen, and PAI-1 activity were all significantly higher in stroke patients compared with controls (all p < 0.0001); the level of tPA activity was significantly lower in patients than that in controls ( p < 0.0001). These markers did not change much at different time points within 72 h. In stroke group, P-selectin concentration was highly correlated to PAI-1 activity ( r = 0.8433, p < 0.001), but not to tPA antigen ( r = −0.1752, p > 0.05), and tPA activity ( r = 0.2465, p > 0.05), which was further confirmed in the multiple linear regression analysis ( F = 47.052, p < 0.0001). Our results indicate increased platelet activation and decreased fibrinolysis in patients with acute atherosclerotic ischemic stroke. Increased platelet activation may be correlated with decreased fibrinolysis.

Characteristics of Garganica goat milk and Cacioricotta cheese

A survey was carried out in four Garganica flocks (FL1, FL2, FL3 and FL4), representative of different flock management, for achieving information on the hygienic and nutritional properties of Garganica goat milk and their impact on Cacioricotta cheese quality. Bulk milk was analyzed for pH, total protein, casein and whey protein, nitrogen fractions, fat, lactose and somatic cell count (SCC). Cacioricotta cheeses were manufactured from the milk of each flock according to a traditional protocol and analyzed for pH, moisture and NaCl contents, water activity, nitrogen fractions and fat content. Plasmin and plasminogen activity were detected in milk and cheese. Skim pooled milk and pH 4.6 soluble and insoluble fractions of the cheese were analyzed using alkaline Urea-PAGE. Garganica goat milk composition was in the range reported in literature for this breed. Somatic cell counts were higher ( P < 0.001) and protein and casein contents lower in the FL2 and the FL3 than in the FL1 and the FL4 flocks. No differences were found among flocks in the electrophoretic profile of milk. Marked changes were observed in cheese composition across flocks. A higher number of bands was detected in the Urea-PAGE of pH 4.6 soluble fractions from FL1 and FL4 cheeses compared to FL2 and FL3 cheeses together with a higher percentage of nitrogen fractions from casein degradation. SCC was correlated negatively with milk protein and casein contents and with cheese fat content. Marked changes observed in milk and cheese composition suggest that more definite rules of flock management and milk processing are required for improving and standardizing Cacioricotta cheese quality. Results also indicate that the control of sanitation of housing and milking procedures is critical for optimizing the nutritional and hygienic characteristics of Garganica goat milk and proteolysis occurring in Cacioricotta cheese during ripening.

Trombophilic screening for nonarteritic anterior ischemic optic neuropathy

Nonarteritic anterior ischemic optic neuropathy (NAION) is an ischemic infarction of the optic nerve head, frequently leading to sudden, mostly irreversible loss of vision. In this study blood thrombophilic factors, as well as cardiovascular risk factors were investigated for their relevance to this pathology. Trombophilic risk factors so far not evaluated were included in the study. 37 NAION patients (4 with sequential second eye involvement) and 81 matched control subjects were examined. From blood, protein C, protein S, antithrombin, von Willebrand antigen levels (vWFAg), and factor V (Leiden) mutation, factor VIIIC level, plasminogen activity, lipoprotein (a) and fibrinogen levels, and presence of anticardiolipin antibodies were investigated. Possibly relevant pathologies [e.g. diabetes mellitus (DM), hypertension, and ischemic heart disease] were also registered. Elevated Lp(a) and vWFAg levels, DM, F V (Leiden), hypercholesterolemia, and hyperfibinogenemia proved to be significant risk factors associated with NAION. Forward stepwise logistic regression analysis revealed that high Lp(a), DM, and FV (Leiden) were the main predictive components, with odds ratios 16.88 (p=0.012), 5.78 (p=0.022) and 4.44 (p=0.033), respectively. Based on our results it appears that thrombophilia is likely to contribute to the development of NAION besides vascular damage due to the presence of cardiovascular risk factors. Further data are needed, however, to justify the suggested use of secondary prophylaxis using anticoagulant/antiplatelet therapy.

Hormone replacement therapy and hemostasis: Effects in Brazilian postmenopausal women

Objective To evaluate the impact that administration of transdermal estradiol gel combined with medroxyprogesterone acetate (MPA) has on hemostasis. Methods In this open prospective longitudinal study, thirty postmenopausal women received transdermal estradiol gel (1 mg/day) continuously combined with oral MPA (5 mg/day) for 12 days/month. The following parameters were determined: prothrombin time (PT), activated partial thromboplastin time (aPTT), factors VII, X, and XII activity, fibrinogen levels, thrombin-antithrombin complex levels, protein C and S antigen, antithrombin activity, plasminogen activator inhibitor type 1 (PAI-1) antigen, tissue-type plasminogen activator (t-PA) antigen, plasminogen activity and fibrin degradation products (FbDP) antigen. They were evaluated before and after 6 months of treatment. Results There was a significant decrease in factor VII activity ( P = 0.001), factor X activity ( P = 0.016), protein C antigen ( P = 0.022), antithrombin activity ( P = 0.025), plasminogen activity ( P = 0.023), t-PA antigen ( P = 0.043) and FbDP antigen ( P = 0.048) compared with baseline values. Conclusion The results suggest that the treatment with transdermal estradiol gel combined with MPA avoids any major activation of coagulation and does not produce any overall effect on fibrinolysis. Therefore, this treatment might provide interesting effects on hemostasis in postmenopausal Brazilian women.