scholarly journals THE FIBRINOLYTIC ALTERATION ASSOCIATED WITH DAILY ADMINISTRATION OF SILDENAFIL

Author(s):  
Fathelrahman M Hassan

Objective: The objective of this study was to determine the fibrinolytic alteration associated with daily administration of sildenafil.Methods: A total of 12 adult male rabbits without mortality rate had been fed standard and subdivided into four groups; their average weight was 1.5, 2.5, 1.9, and 2 kg randomly selected during the period of March 2012–July 2013. Depending on weight, the control groups (2.25 mg/1.5 kg day) and sildenafil groups (3 mg/2 kg/day, 2.85 mg/1.9 kg/day, and 1.7 mg/2.5 kg/day) were injected by normal saline and sildenafil concentration, respectively to create four groups, every group was composed of three rabbits; saline rabbit (control group, n=3) and sildenafil rabbits (sildenafil group, n=9). All rabbit’s plasma samples have been investigated for prothrombin time, activated partial thromboplastin time, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1+2, tissues plasminogen activator (tPA), plasmin antiplasmin (PAP), plasminogen, and D-dimer after 24 h of administration.Results: The PAP level was significantly (p<0.05) decreased following sildenafil injection. Sildenafil-injected (3 mg/ml) rabbits had decreased the means of PAI-1 and mean tPA, as early as 1-day post-injection, with a considerable lower PAP first determined 3 days after injection that continued into each rabbit 2 and 3.Conclusion: Better strategies are to initiate and manipulate this drug ought to reduce the chance of each thrombosis and hemorrhage, at the same time as minimizing the need for laboratory monitoring with the aid of the use of PAI-1, tPA, and PAP checks.

1999 ◽  
Vol 82 (07) ◽  
pp. 104-108 ◽  
Author(s):  
Franck Paganelli ◽  
Marie Christine Alessi ◽  
Pierre Morange ◽  
Jean Michel Maixent ◽  
Samuel Lévy ◽  
...  

Summary Background: Type 1 plasminogen activator inhibitor (PAI-1) is considered to be risk factor for acute myocardial infarction (AMI). A rebound of circulating PAI-1 has been reported after rt-PA administration. We investigated the relationships between PAI-1 levels before and after thrombolytic therapy with streptokinase (SK) as compared to rt-PA and the patency of infarct-related arteries. Methods and Results: Fifty five consecutive patients with acute MI were randomized to strep-tokinase or rt-PA. The plasma PAI-1 levels were studied before and serially within 24 h after thrombolytic administration. Vessel patency was assessed by an angiogram at 5 ± 1days. The PAI-1 levels increased significantly with both rt-PA and SK as shown by the levels obtained from a control group of 10 patients treated with coronary angioplasty alone. However, the area under the PAI-1 curve was significantly higher with SK than with rt-PA (p <0.01) and the plasma PAI-1 levels peaked later with SK than with rt-PA (18 h versus 3 h respectively). Conversely to PAI-1 levels on admission, the PAI-1 levels after thrombolysis were related to vessel patency. Plasma PAI-1 levels 6 and 18 h after SK therapy and the area under the PAI-1 curve were significantly higher in patients with occluded arteries (p <0.002, p <0.04 and p <0.05 respectively).The same tendency was observed in the t-PA group without reaching significance. Conclusions: This study showed that the PAI-1 level increase is more pronounced after SK treatment than after t-PA treatment. There is a relationship between increased PAI-1 levels after thrombolytic therapy and poor patency. Therapeutic approaches aimed at quenching PAI-1 activity after thrombolysis might be of interest to improve the efficacy of thrombolytic therapy for acute myocardial infarction.


2021 ◽  
Vol 43 (5) ◽  
pp. 400-409
Author(s):  
Roya Bagheri ◽  
Seyed ali Rahmani ◽  
Leila Khoramifar ◽  
Solmaz Ilkhichoui

Background. Parental chromosomal abnormalities as well as changes in genes encoding thrombophilic factors are common causes of recurrent abortions. One of the causes of thrombophilia is Factor II (F2) gene mutation (G20210A) and plasminogen activator inhibitor gene (PAI-1) polymorphism (4G/5G). Therefore, the present study aimed to investigate the frequency of chromosomal abnormalities and the association of thrombophilic gene polymorphisms in patients with abortion in northwestern Iran. Methods. In the present case-control study, cytogenetic analysis of 60 couples with a history of recurrent abortions was performed by the standard 72-hour culture of lymphocytes and G-banding. The polymorphism (5G/4G) of PAI-1 gene and the mutation (G20210A) of F2 genes were evaluated using RFLP-PCR and ARMS-PCR molecular methods, respectively. The obtained data were analyzed using statistical software. Results. No significant abnormalities affecting abortion were observed in cytogenetic studies; in the molecular study, the frequency of the 4G allele in patients and control groups were 54.2% and 33.3%, respectively; the frequency of 5G allele in the patients and control groups were 45.8% and 66.8%, respectively. The frequency of 5G/5G and 4G/5G genotypes is 25.0% and 41.6% in the patient group, and 55.0% and 23.3% in the control group, respectively. Also, the frequency of 4G/4G genotype in patients and controls were 33.3% and 21.6%, respectively. Conclusion. The results of this study show that there is a significant relationship between the frequency of the 4G allele of the PAI-1 gene with susceptibility to recurrent abortions in northwestern women, while no was relationship between F2 gene mutation and recurrent abortions was observed.


2005 ◽  
Vol 20 (1) ◽  
pp. 48-52 ◽  
Author(s):  
A Mansilha ◽  
F Araújo ◽  
M Severo ◽  
S M Sampaio ◽  
T Toledo ◽  
...  

Objective: To evaluate the association between the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene and deep venous thrombosis (DVT) in young people. Methods: Prevalence of the 4G/5G polymorphism was investigated using DNA analysis in a population of 81 consecutive and unrelated patients with an objectively documented first episode of DVT under 40 years old and in a control group of 88 healthy subjects. Results: The frequency of genotypes among patients was 0.27 4G/4G, 0.49 4G/5G and 0.23 5G/5G, corresponding to a frequency of 0.52 for the 4G allele. In the control group the results were, respectively, 0.24, 0.44 and 0.32, corresponding to a frequency of 0.46 for the 4G allele. The odds ratio (OR) for homozygous 4G genotype was 1.5 (95% confidence interval: 0.7–3.6), which was not statistically significant ( P = 0.51). Conclusion: In this study, the 4G/5G polymorphism in the promoter of the PAI-1 gene, including the homozygous 4G genotype, was not associated with a significantly increased risk of DVT in young people.


2003 ◽  
Vol 50 (1) ◽  
pp. 279-289 ◽  
Author(s):  
Natalia Yu Yevdokimova ◽  
Larisa D Veselovska ◽  
Genrietta K Gogolinska ◽  
Olexandra M Buchanevich ◽  
Galina V Kosyakova ◽  
...  

Fibrin split product D-dimer (DD) is most probably involved in the development of vascular disorders. At 1.5 microM concentration DD inhibited the incorporation of D-[1-(3)H]glucosamine hydrochloride and [2-(14)C]acetate x Na into pericellular heparan sulphate (HS) of rabbit coronary endothelial cells without affecting other groups of glycosaminoglycans (GAGs). At the same time, DD reduced HS ability to bind antithrombin (AT) and suppressed NO production. The effect of DD on pericellular GAGs was similar to that of N(omega)-methyl-L-arginine, the competitive inhibitor of endothelial NO synthase (eNOS). L-Ascorbic acid, eNOS activator, increased the level of endogenous NO in the DD-treated cells, and restored HS accumulation and antithrombin binding. It is suggested that DD influence on endothelial HS may be mediated by NO production. Another effect of DD, namely, stimulation of plasminogen activator inhibitor-1 (PAI-1) secretion did not depend on the NO level. The decreased HS content, reduced anticoagulant properties of HS, and increased PAI-1 secretion disorganized the endothelial matrix, and promoted fibrin formation and vascular damage. This points to DD as an important factor in the development of vascular disorders.


2021 ◽  
Author(s):  
FATMA BURCU BELEN APAK ◽  
Gulbahar Yuce ◽  
Deniz Ilhan Topcu ◽  
Ayse Gultekingil ◽  
Yunus Emre Felek ◽  
...  

Abstract Background: A substantial group of patients suffer coagulopathy of Covid-19 (CAC) and are presented with thrombosis. The pathogenesis involved in CAC is not fully understood.Objectives: We evaluated the hemostatic and inflammatory parameters of 51 hospitalized Covid-19 adult patients and 21 controls. The parameters analyzed were danger signal molecule (High molecular weight group box protein-1/HMGBP-1), platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen, endothelial protein C receptor (EPCR), soluble E-selectin, soluble P-selectin, thrombomodulin, tissue plasminogen activator (TPA), plasminogen activator inhibitor-1 (PAI-1), soluble fibrin monomer complex (SFMC), platelet-derived microparticles (PDMP), β-thromboglobulin, antithrombin and protein C. The main objective of our study was to investigate which part of the hemostatic system was mostly affected at the admission of Covid-19 patients and whether these parameters could differentiate intensive care unit (ICU) and non-ICU patients. Patients and Methods:In this prospective case-control study, 51 patients ≥18 years who are hospitalized with the diagnosis of Covid-19 and 21 healthy control subjects were included. We divided the patients into two groups according to their medical progress, either into ICU and non-ICU group. Regarding the outcome, patients were again categorized as survivor and non-survivor groups. Blood samples were collected from patients at admission at the time of hospitalization before administration of any treatment for Covid-19. The analyzes of the study were made with the IBM SPSS V22 program. p < 0.05 was considered statistically significant.Results:A total of 51 adult patients (F/M: 24/27) (13 ICU and 38 non-ICU) were included in the study cohort. The mean age of the patients was 68.1 ± 14.4 years. The control group consisted of 21 age and sex-matched healthy individuals. All of the patients were hospitalized, in a group of 13 patients, Covid-19 progressed to severe form and were hospitalized at ICU. We found out that the levels of fibrinogen, prothrombin time (PT), endothelial protein-C receptor (EPCR), D-dimer, soluble E-selectin, soluble P-selectin, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (TPA) were increased; whereas, the levels of soluble fibrin monomer complex (SFMC), platelet-derived microparticles (PDMP), antithrombin and protein-C were decreased in Covid-19 patients compared to the control group at hospital admission. Tissue plasminogen activator was the only marker that had a significantly different median level between ICU and non-ICU groups (p<0.001).Conclusions:In accordance with the previous literature, we showed that Covid-19 associated coagulopathy is distinct from sepsis-induced DIC with prominent early endothelial involvement and fibrinolytic shut-down. Reconstruction of endothelial function at early stages of infection may protect patients to progress to ICU hospitalization. We believe that after considering the patient’s bleeding risk, early administration of LMWH therapy at Covid-19 even in at outpatient setting may be useful both for restoring endothelial function and anticoagulation. The intensity of anticoagulation in non-ICU and ICU Covid-19 patients should be clarified with further studies.


2017 ◽  
Vol 138 (2) ◽  
pp. 111-115
Author(s):  
Petra Bubalo ◽  
Iva Buterin ◽  
Zrinko Šalek ◽  
Vesna Ðogić ◽  
Silva Zupančić-Šalek

Aim: The objective of this study was to investigate a possible correlation between the plasminogen activator inhibitor-1 (PAI-1) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms and unexplained spontaneous miscarriages (SM). Materials and Methods: PAI-1 polymorphisms were evaluated in 150 women with pregnancy in their history. One hundred women with a history of SM formed the study group and 50 women with normal pregnancies served as the control group. Also, the combination of PAI-1 and MTHFR polymorphisms were evaluated in 138 women out of a total of 150, which included 92 women with SM in their history compared to 46 women in the control group. For statistical analysis, χ2 test, Phi, and Cramer V tests were used; p < 0.05 was taken as a statistically significant result. Results: Our findings show: (a) the correlation between SM and PAI-1 mutations reaches statistical significance (p = 0.026); (b) there was a statistically significant difference between heterozygous PAI-1 in women with only 1 SM compared to the control group (p = 0.047); (c) the comparison of combinations of both mutations, PAI-1 and MTHFR, with the control group demonstrates statistical significance in favor of women with SM and both mutations (p = 0.022). Conclusion: PAI-1 and MTHFR polymorphisms may play an important role in pregnancy complications because heterozygous PAI-1 mutations and a combination of both PAI-1 and MTHFR mutations might contribute to SM.


2004 ◽  
Vol 132 (5-6) ◽  
pp. 143-147 ◽  
Author(s):  
Zagorka Jovanovic ◽  
Mirka Ilic ◽  
Jasna Zidverc-Trajkovic ◽  
Aleksandra Pavlovic ◽  
Milija Mijajlovic ◽  
...  

Fibrinolytic activity in the acute stroke was examined by monitoring the level of plasminogen activator inhibitor-1 (PAI-1), as one of the indicators of fibrinolytic activity. Given the role of PAI-1 in the processes of atherogenesis and thrombogenesis, plasma PAI-1 level was measured in 59 patients (up to 50 years of age) with atherothrombotic stroke (verified by computed tomography scanning or magnetic resonance imaging of brain) in the period from 12 to 24 hours (I analysis) and 30 days after the onset of stroke (II analysis); then, it was correlated with plasma PAI-1 level in the control group (57 healthy subjects), which was 2.86?0.70 U/ml. It was found that PAI-1 level was significantly higher in the acute stroke (I analysis: PAI-1 =4.10?1.40 U/ml, p<0.001; II analysis: PAI-1 =3.64+0.90 U/ml, p<0.001), while fibrinolytic activity was lower, especially on the first day from the stroke that was not completely increased even after 30 days. There was no difference in PAI-1 levels between the subgroups of patients with infarction and lacunar cerebral ischemia (p>0.05), as well as between females and males (p>0.05). Along with significantly increased fibrinogen level (4.65?1 g/l, in the controls - 2.83?0.64 g/l, p<0.001), significantly higher triglycerides (2.04?0.76 mmol/l, in the controls - 1.38+0.54 mmol/l, p<0.001) and lipoproteins(a) (0.405?0.29 g/l, in the controls -0.172?0.14 g/l, p<0.001) were found, correlating with higher plasma PAI-1 level in these patients. The increased plasma level of PAI-1 pointed to possibility of decreased fibrinolytic activity in pathogenesis of ischemie stroke, as well as, risk of reinsult, which had been the greatest after the onset of stroke and declined gradually within several weeks.


2021 ◽  
Vol 9 (B) ◽  
pp. 726-733
Author(s):  
Yelena Laryushina ◽  
Viktoriya Parakhina ◽  
Lyudmila Turgunova ◽  
Dinara Sheryazdanova ◽  
Raushan Dosmagambetova ◽  
...  

Background. Plasminogen activator inhibitor-1(PAI-1) is a marker of endothelial dysfunction(ED) and a predictor of both the development of type 2 diabetes mellitus, and a cardiovascular event(CVE). Its role in the CVE development was sufficiently studied in patients without carbohydrate metabolism disorders, and understudied in patients with prediabetes. Aim: the research interest is the study of PAI-1 in patients with prediabetes and its effect on the CVE development. Materials and methods. The case-control study of 168 patients aged from 18 to 65 was carried out among the local population from January to December 2019.After clinical examination, patients were divided into 3 groups: group 1 (n=55)– patients with prediabetes and with CVE; group 2 (n=93) - patients with prediabetes and without CVE; the control group n=20. Results. Differences in PAI-1 level were found in groups 1 (Me=30718.6 pg/ml) and 2 (Me=24692.0 pg/ml; p≤0.001), even greater differences were found in both groups compared to the control one (p≤0.001). The correlation analysis has found in both group influence such IR indicators as fasting glucose, IR-HOMA index, glucagon, C-peptide to elevation of PAI-1. These findings indicate that with an elevation of the PAI-1 level, the concentration of fasting glucose, glucagon, C-peptide and scores of IR-HOMA index increase in both group. The Binary regression analysis has demonstrated, that an elevation of the PAI-1 biomarker increases the likelihood of CVE by 3.3 fold in patients with prediabetes (p≤0.01). In addition to, a model has been derived for assessing the risk of cardiovascular events in patients with prediabetes. Conclusions. Elevation of PAI-1 concentration is associated with insulin resistance which leads to ED, and further development risk of CVE in patients with prediabetes.


1989 ◽  
Vol 61 (03) ◽  
pp. 459-462 ◽  
Author(s):  
Gerard Pralong ◽  
Thierry Calandra ◽  
Michel-P Glausef ◽  
Joop Schellekens ◽  
Jan Verhoef ◽  
...  

SummaryThe prognostic value of plasminogen activator inhibitor type 1 (PAI-1) in septic shock was investigated in 52 patients with septic shock. The patients had significantly elevated serum PAI-1 levels with respect to the control group (p = 0.002). In patients not having a rapidly fatal underlying disease, PAI-1 was significantly higher in patients dying within a week after onset of shock than in survivors (median PAI-1: 900 and 307 ng/ml, respectively; p = 0.001). The analysis of the distribution of PAI-1 levels permitted retrospectively to determine a threshold level of PAI-1 which had prognostic significance. Mortality was 71% in patients with serum PAI-1 above 550 ng/ml, whereas only two patients (6%) having a PAI-1 below 550 ng/ml died within a week.Thus, in patients with septic shock, PAI-1 appears to have a strong predictive value as to mortality. This early marker may help the clinician in identifying a subgroup of patients particularly at risk.


Author(s):  
Stella Urekweru Ken-Ezihuo ◽  
Barinaaziga Sunday Mbeera ◽  
Chiatugu Nancy Ibeh ◽  
Zacchaeus Awortu Jeremiah

Aim: The study was designed to comparatively assess the degree of fibrinolytic response amongst   malaria-positive pregnant women, and non-malaria positive subjects in Rivers State, Nigeria. Methods: The study area covered University of Port Harcourt Teaching Hospital, Port Harcourt [UPTH] and Rivers State University Teaching Hospital, [RSUTH] both in Port Harcourt metropolis Rivers State.  It was a cross-sectional study carried out on a total of two hundred and forty female attendees at the obstetrics and gynecology clinics of the two hospitals. The subjects were grouped into three comprising of eighty subjects in each group; malarious pregnant women, non- malarious pregnant women and apparently healthy non-pregnant women. Venous blood sample measuring 5 milliliter volume was drawn from each subject, The sample was dispensed into two separate EDTA anticoagulant bottles, 3 milliliter and 2 milliliter meant for measuring the levels of markers of fibrinolysis which were Plasminogen, Plasminogen activator inhibitor-1, Plasminogen activator inhibitor-2, Tissue Plasminogen activator, alpha-2-antiplasmin, D-dimers and fibrinogen, and      preparation of blood films for malaria microscopy respectively. Results: Fibrinogen result; 760.44±16.18 ng/ml of malaria-positive pregnant women was elevated compared to the malaria-negative women; 697.70±18.84 ng/ml and the non-pregnant control values of 704.73±15.25 ng/ml. These values were significantly different [P<.011] between the study groups. Results of tissue plasminogen activator [tPA]; 46.39±2.69 ng/ml, D-dimer; 77.64±6.94 ng/ml, plasminogen activator inhibitor-1 [PAI-1]; 89.73±2.14 ng/ml, plasminogen activator inhibitor-2 [PAI-2]; 568.00±12.51 ng/ml, plasminogen; 23.82±0.75 ng/ml and 2-antiplasmin; 1314.06±34.64 ng/ml of the malaria-positive pregnant women were significantly different [P=0.0001] from  non-positive pregnant women; tPA; 28.87±1.38 ng/ml, D-dimer; 53.90±1.18 ng/ml., PAI-1; 80.00± 1.81 ng/ml, PAI-2; 456.31±5.94 ng/ml, Plasminogen; 16.63±0.67 ng/ml and 2-antiplasmin; 1130.61±29.74 ng/ml . Both results were significantly different [P=0.0001] from the non-pregnant control group; tPA; 31.34±1.64 ng/ml, D-dimer; 30.24±1.04 ng/ml, PAI-1; 65,47±2,33 ng/ml, PAI-2; 427.86±6.95 ng/ml, plasminogen; 16.49±0.04 ng/ml and 2-antiplasmin; 1016.98±24.51 ng/ml. Conclusion: The study witnessed significantly high concentrations of fibrinolytic markers in malaria-positive pregnant women. This could be due to compromised endothelial cell function resulting to overproduction of biomarkers of fibrinolysis. The implication is thrombus formation and excessive bleeding in pregnancy which could lead to miscarriages, fetal death or maternal mortality.


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