-
Journal of Stroke and Cerebrovascular... Feb 2018Intravenous thrombolysis using tissue plasminogen activator (tPA) improves significantly the neurologic function in patients with acute ischemic stroke (AIS). However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intravenous thrombolysis using tissue plasminogen activator (tPA) improves significantly the neurologic function in patients with acute ischemic stroke (AIS). However, it brings financial burden to patients and is associated with symptomatic intracranial hemorrhage (SICH). Whether low-dose tPA can effectively reduce SICH and has the same efficacy as standard-dose tPA is still controversial.
METHODS
We searched for English clinical trials published before March, 2017on the comparison of the efficacy and safety between low and standard dose of tPA in the treatment of AIS using MEDLINE, Embase, and Cochrane Library. The modified Rankin scale (mRS) score was used as the primary efficacy outcome. The mRS1 corresponded to 0-1, whereas mRS2 corresponded to 0-2. The SICH and mortality were adopted as primary safety outcomes.
RESULTS
Twelve high-quality studies were selected, including 7686 patients (low-dose: 2888, standard-dose: 4798). With no statistical heterogeneity, the fixed effects model was adopted in the analysis. Similarly to standard doses, low-dose tPA improved the mRS scores (mRS1: odds ratio [OR] = .92, 95% confidence interval [CI] .84-1.02; P = .12; mRS2: OR = .97, 95% CI .88-1.08; P = .57). Compared with standard-dose tPA, low-dose tPA reduced the incidence of SICH (by National Institute of Neurological Disorders and Stroke [NINDS] definition: OR = .71, 95% CI .57-0.89; P = .003; by Safe Implementation of Thrombolysis in Stroke Monitoring Study [SITS-MOST] definition: OR = .64, 95% CI .42-0.99; P = .04), while both reduced mortality (OR = .87, 95% CI .74-1.02; P = .08).
CONCLUSIONS
Low-dose tPA is comparable to standard-dose tPA in improving the neurologic function and reducing mortality in AIS patients. Moreover, low-dose tPA can reduce the incidence of SICH compared with standard-dose tPA. Therefore, low-dose tPA is highly recommended in AIS patients.
Topics: Brain Ischemia; Chi-Square Distribution; Disability Evaluation; Fibrinolytic Agents; Humans; Infusions, Intravenous; Intracranial Hemorrhages; Odds Ratio; Recovery of Function; Risk Factors; Stroke; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 29111341
DOI: 10.1016/j.jstrokecerebrovasdis.2017.09.014 -
Oncotarget Apr 2017The urokinase plasminogen activation (uPA) system is a crucial pathway for tumour invasion and establishment of metastasis. Although there is good evidence that uPA... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The urokinase plasminogen activation (uPA) system is a crucial pathway for tumour invasion and establishment of metastasis. Although there is good evidence that uPA system expression is a clinically relevant biomarker in some solid tumours, its role in gastroesophageal cancer is uncertain.
RESULTS
We identified 22 studies encompassing 1966 patients which fulfilled the inclusion criteria. uPA, uPAR, or PAI-1 expression is significantly associated with high risk clinicopathological features. High uPA expression is associated with a shorter RFS (HR 1.90 95% 1.16-3.11, p = 0.01) and OS (HR 2.21 95% CI 1.74-2.80, p < 0.0001). High uPAR expression is associated with poorer OS (HR 2.21 95%CI 1.82-2.69, p < 0.0001). High PAI-1 expression is associated with shorter RFS (HR 1.96 96% CI 1.07-3.58, p = 0.03) and OS (HR 1.84 95%CI 1.28-2.64, p < 0.0001). There was no significant association between PAI-2 expression and OS (HR 0.97 95%CI 0.48-1.94, p < 0.92) although data was limited.
MATERIALS AND METHODS
We undertook a systematic review evaluating expression of uPA, urokinase plasminogen activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1/SerpinE1) and plasminogen activator inhibitor-2 (PAI-2/SerpinB2) on primary oesophageal, gastro-oesophageal junction, and gastric adenocarcinomas. We performed a meta-analysis of clinicopathological associations, overall survival (OS) and recurrence free survival (RFS).
CONCLUSIONS
We conclude that the uPA system is a clinically relevant biomarker in primary gastroesophageal cancer, with higher expression of uPA, uPAR and PAI-1 associated with higher risk disease and poorer prognosis. This also highlights the potential utility of the uPA system as a therapeutic target for improved treatment strategies.
Topics: Adenocarcinoma; Biomarkers, Tumor; Esophageal Neoplasms; Esophagogastric Junction; Humans; Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 2; Prognosis; Receptors, Urokinase Plasminogen Activator; Stomach Neoplasms; Survival Analysis; Urokinase-Type Plasminogen Activator
PubMed: 28416743
DOI: 10.18632/oncotarget.15485 -
Journal of the American Heart... May 2017Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk.
METHODS AND RESULTS
To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol.
CONCLUSIONS
Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction.
Topics: Biomarkers; Blood Glucose; Coronary Disease; Fibrinolysis; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Incidence; Lipoproteins, HDL; Mendelian Randomization Analysis; Multivariate Analysis; Observational Studies as Topic; Odds Ratio; Plasminogen Activator Inhibitor 1; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors
PubMed: 28550093
DOI: 10.1161/JAHA.116.004918 -
Brain, Behavior, and Immunity Jun 2024There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a... (Review)
Review
BACKGROUND
There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of chronic inflammation, which provides a more stable index of systemic inflammation than more widely used biomarkers. This review aims to synthesise studies that measured suPAR concentrations in individuals with a psychiatric disorder, to determine if these concentrations are altered in comparison to healthy participants.
METHOD
Comprehensive literature searches from inception to October 2023 were conducted of five relevant databases (PubMed, Web of Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses were performed to compare the standardised mean difference of blood suPAR levels (i.e. plasma or serum) for individuals with any psychiatric disorder relative to controls. Separate meta-analyses of suPAR levels were conducted for individuals with schizophrenia or other psychotic disorder and depressive disorder. Risk of bias was assessed using the Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding studies at high risk of bias, and analyses of studies that measured suPAR concentrations either in serum or in plasma separately.
RESULTS
The literature search identified 149 records. Ten full-text studies were screened for eligibility and 9 studies were included for review. Primary analyses revealed no significant difference in suPAR levels between individuals with any psychiatric disorder compared to controls (k = 7, SMD = 0.42, 95 % CI [-0.20, 1.04]). However, those with depressive disorder had elevated suPAR levels relative to controls (k = 3, SMD = 0.61, 95 % CI [0.34, 0.87]). Similarly, secondary analyses showed no evidence of a significant difference in suPAR levels in individuals with any psychiatric disorder when studies at high risk of bias were excluded (k = 6, SMD = 0.54, 95 % CI [-0.14, 1.22]), but elevated suPAR concentrations for those with schizophrenia or other psychotic disorder were found (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). Furthermore, studies that analysed plasma suPAR concentrations found elevated plasma suPAR levels in individuals with any psychiatric disorder relative to controls (k = 5, SMD = 0.84, 95 % CI [0.38, 1.29]), while studies measuring serum suPAR levels in any psychiatric disorder did not find a difference (k = 2, SMD = -0.61, 95 % CI [-1.27, 0.04]). For plasma, elevated suPAR concentrations were also identified for those with schizophrenia or other psychotic disorder (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]).
DISCUSSION
When studies measuring either only serum or only plasma suPAR were considered, no significant difference in suPAR levels were observed between psychiatric disorder groups, although significantly elevated suPAR levels were detected in those with moderate to severe depressive disorder. However, plasma suPAR levels were significantly elevated in those with any psychiatric disorder relative to controls, while no difference in serum samples was found. A similar finding was reported for schizophrenia or other psychotic disorder. The plasma findings suggest that chronic inflammatory dysregulation may contribute to the pathology of schizophrenia and depressive disorder. Future longitudinal studies are required to fully elucidate the role of this marker in the psychopathology of these disorders.
PubMed: 38857636
DOI: 10.1016/j.bbi.2024.06.003 -
Stroke Jan 2018Although current guidelines advocate pretreatment with intravenous thrombolysis (IVT) in all eligible patients with acute ischemic stroke with large-vessel occlusion... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Although current guidelines advocate pretreatment with intravenous thrombolysis (IVT) in all eligible patients with acute ischemic stroke with large-vessel occlusion before mechanical thrombectomy, there are observational data questioning the efficacy of this approach. One of the main arguments in favor of IVT pretreatment is the potential for tissue-type plasminogen activator-induced successful reperfusion (SR) before the onset of endovascular procedure.
METHODS
We performed a systematic review and meta-analysis of randomized controlled clinical trials and observational cohorts providing rates of SR with IVT in patients with large-vessel occlusion before the initiation of mechanical thrombectomy. We also performed subgroup analyses according to study type (randomized controlled clinical trials versus observational) and according to the inclusion per protocol of patients with tandem (intracranial/extracranial) occlusions.
RESULTS
We identified 13 eligible studies (7 randomized controlled clinical trials and 6 observational cohorts), including 1561 patients with acute ischemic stroke (median National Institutes of Health Stroke Scale score, 17) with large-vessel occlusion. SR following IVT and before mechanical thrombectomy was documented in 11% (95% confidence interval, 7%-16%), with no difference among cohorts derived from randomized controlled clinical trials and observational studies. There was significant heterogeneity across included studies both in the overall analysis and among subgroups (I>84%; for Cochran Q, <0.001). Higher tissue-type plasminogen activator-induced SR rates were documented in studies reporting the exclusion of tandem occlusions (17%; 95% confidence interval, 11%-23%) compared with the rest (7%; 95% confidence interval, 4%-11%; for subgroup differences, 0.003).
CONCLUSIONS
Pretreatment with systemic thrombolysis in patients with large-vessel occlusion eligible for mechanical thrombectomy results in SR in 1 of 10 cases, negating the need for additional endovascular reperfusion. Tandem occlusions seem to be the least responsive to IVT pretreatment.
Topics: Brain Ischemia; Cerebral Veins; Endovascular Procedures; Female; Humans; Male; Randomized Controlled Trials as Topic; Reperfusion; Stroke; Thrombectomy; Thrombolytic Therapy
PubMed: 29212743
DOI: 10.1161/STROKEAHA.117.019261 -
International Journal of Stroke :... Dec 2017Background Recombinant tissue plasminogen activator is the only FDA-approved thrombolytic agent for acute stroke treatment. However, there are concerns that recombinant... (Meta-Analysis)
Meta-Analysis Review
Background Recombinant tissue plasminogen activator is the only FDA-approved thrombolytic agent for acute stroke treatment. However, there are concerns that recombinant tissue plasminogen activator may increase the risk of seizures (including early and late seizures). Aims We performed a systematic review to assess the incidence of seizures and the association of recombinant tissue plasminogen activator with seizure occurrence. Summary of review We searched major databases for articles published between 1995 and February 2016. The pooled incidence of post-stroke seizure, early seizure, late seizure, and seizures sub-types was estimated overall and by status for recombinant tissue plasminogen activator treatment, and unadjusted odds ratio used to quantify the effects of recombinant tissue plasminogen activator on post-stroke seizure occurrence. In all, 4362 stroke participants were included with 49-63% being male and median age ranging from 68 to 71 years. A total of 792 received recombinant tissue plasminogen activator. The incidence of post-stroke seizure per 1000 participants (95% CI) was 95 (31-196) overall, 113 (49-202) in recombinant tissue plasminogen activator and 169 (6-326) in non-recombinant tissue plasminogen activator-treated (all heterogeneity- p<0.0001). Incidence of early seizure per 1000 (95% CI) was 35 (27-45) overall; 34 (22-50) among recombinant tissue plasminogen activator-treated patients, and 36 (25-48) among recombinant tissue plasminogen activator naïve participants (all heterogeneity- p > 0.826). The pool incidence rate per 1000 (95% CI) of late seizure was 84 (4-263), 46 (2-145), and 212 (184-241), respectively, in the overall, the recombinant tissue plasminogen activator-treated group and non-recombinant tissue plasminogen activator-treated group (heterogeneity for overall and recombinant tissue plasminogen activator-treated group < 0.0001, non-recombinant tissue plasminogen activator naïve = 0.999). The pooled odds ratio for post-stroke seizure (recombinant tissue plasminogen activator vs. no recombinant tissue plasminogen activator) was 0.94 (95% CI: 0. 17-5.26, heterogeneity- p < 0.0001). The pooled incidence per 1000 participants (95% CI) was 30 (0-144), 17 (2-49), 16 (2-44), and 9 (0-50), respectively, for focal seizure without impairment of consciousness, focal seizure with impairment of consciousness, generalized convulsive seizure, and status epilepticus; all heterogeneity- p < 0.0003. Accompanying pooled odds ratio (recombinant tissue plasminogen activator vs. no recombinant tissue plasminogen activator) based on one study was always in favor of non-significantly lower risk in recombinant tissue plasminogen activator-treated patients (all heterogeneity- p = 1). There were insufficient data to compute pooled odds ratio for early and late seizure. Conclusions Seizures affect nearly 1 out of every 10 stroke patients with inconclusive suggestion that rates are similar in recombinant tissue plasminogen activator-treated and recombinant tissue plasminogen activator naïve patients. Large prospective studies are needed to better understand the relationship between recombinant tissue plasminogen activator and post-stroke seizure occurrence.
Topics: Animals; Fibrinolytic Agents; Humans; Incidence; Recombinant Proteins; Seizures; Stroke; Tissue Plasminogen Activator
PubMed: 28872451
DOI: 10.1177/1747493017729239 -
Ear, Nose, & Throat Journal Nov 2022Previous studies revealed that the prothrombotic factors in patients with obstructive sleep apnea (OSA) remain controversial. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previous studies revealed that the prothrombotic factors in patients with obstructive sleep apnea (OSA) remain controversial.
AIM/OBJECTIVE
The aim of the systematic review is to elucidate the relationship between prothrombotic factors and OSA.
MATERIALS AND METHODS
This systematic review was performed under the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The literature we investigated was extracted from 4 main medical databases (PubMed, Web of Science, Cochrane Library, and Chinese databases) as of February 2020. We used significant weighted mean differences (SMDs) with 95% CIs from random-effects model.
RESULTS
A total of 15 studies comprising 2190 patients were available for the meta-analysis. The pooled results showed that the levels of fibrinogen (SMD = 0.95, 95% CI = 0.26 to 1.65, = .000), vascular endothelial growth factor (SMD = 0.37, 95% CI = -0.90 to 1.63, = .000), and plasminogen activator inhibitor 1 (SMD = 0.61, 95% CI = 0.29 to 0.92, = .040) increased in patients with OSA. There were no statistical differences between groups in terms of d-dimer ( = .108) and platelet counts ( = .233). Subgroup analyses demonstrated that specimen types and age could account for the heterogeneity.
CONCLUSIONS AND SIGNIFICANCE
This meta-analysis indicated the relationship between prothrombotic factors in OSA hypopnea. Obstructive sleep apnea-related effects may underline the importance of considering the dysfunction of the hemostatic system. The prothrombotic factors in OSA can influence making a choice of appropriate therapy.
Topics: Hemostatics; Humans; Plasminogen Activator Inhibitor 1; Sleep Apnea, Obstructive; Vascular Endothelial Growth Factor A
PubMed: 33167693
DOI: 10.1177/0145561320965208 -
The Cochrane Database of Systematic... Jan 2023Acute non-arteritic central retinal artery occlusion (CRAO) occurs as a sudden interruption of the blood supply to the retina and typically results in severe loss of... (Review)
Review
BACKGROUND
Acute non-arteritic central retinal artery occlusion (CRAO) occurs as a sudden interruption of the blood supply to the retina and typically results in severe loss of vision in the affected eye. Although many therapeutic interventions have been proposed, there is no generally agreed upon treatment regimen.
OBJECTIVES
To assess the effects of treatments for acute non-arteritic CRAO.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 15 February 2022.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing any interventions with another treatment in participants with acute non-arteritic CRAO in one or both eyes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and graded the certainty of the body of evidence for primary (mean change in best-corrected visual acuity [BCVA]) and secondary (quality of life and adverse events) outcomes using the GRADE classification.
MAIN RESULTS
We included six RCTs with 223 total participants with acute non-arteritic CRAO; the studies ranged in size from 10 to 84 participants. The included studies varied geographically: one in Australia, one in Austria and Germany, two in China, one in Germany, and one in Italy. We were unable to conduct any meta-analyses due to study heterogeneity. None of the included studies compared the same pair of interventions: 1) tissue plasminogen activator (t-PA) versus intravenous saline; 2) t-PA versus isovolemic hemodilution, eyeball massage, intraocular pressure reduction, and anticoagulation; 3) nitroglycerin, methazolamide, mecobalamin tablets, vitamin B and B injections, puerarin and compound anisodine (also known as 654-2) along with oxygen inhalation, eyeball massage, tube expansion, and anticoagulation compared with and without intravenous recombinant tissue plasminogen activator (rt-PA); 4) transcorneal electrical stimulation (TES) with 0 mA versus with 66% of the participant's individual electrical phosphene threshold (EPT) at 20 Hz (66%) versus with 150% of the participant's individual EPT (150%) at 20 Hz; 5) ophthalmic artery branch retrograde thrombolysis versus superselective ophthalmic artery thrombolysis; and 6) pentoxifylline versus placebo. There was no evidence of an important difference in visual acuity between participants treated with t-PA versus intravenous saline (mean difference [MD] at 1 month -0.15 logMAR, 95% confidence interval [CI] -0.48 to 0.18; 1 study, 16 participants; low certainty evidence); t-PA versus isovolemic hemodilution, eyeball massage, intraocular pressure reduction, and anticoagulation (MD at 1 month -0.00 logMAR, 95% CI -0.24 to 0.23; 1 study, 82 participants; low certainty evidence); and TES with 0 mA versus TES with 66% of EPT at 20 Hz versus TES with 150% of EPT at 20 Hz. Participants treated with t-PA experienced higher rates of serious adverse effects. The other three comparisons did not report statistically significant differences. Other studies reported no data on secondary outcomes (quality of life or adverse events). AUTHORS' CONCLUSIONS: The current research suggests that proposed interventions for acute non-arteritic CRAO may not be better than observation or treatments of any kind such as eyeball massage, oxygen inhalation, tube expansion, and anticoagulation, but the evidence is uncertain. Large, well-designed RCTs are necessary to determine the most effective treatment for acute non-arteritic CRAO.
Topics: Humans; Tissue Plasminogen Activator; Retinal Artery Occlusion; Anticoagulants; China
PubMed: 36715340
DOI: 10.1002/14651858.CD001989.pub3 -
World Neurosurgery Jun 2021The current treatment options for chronic subdural hematoma (CSDH) include burr hole drainage, twist drill drainage, and craniotomy with or without postoperative...
BACKGROUND
The current treatment options for chronic subdural hematoma (CSDH) include burr hole drainage, twist drill drainage, and craniotomy with or without postoperative catheter drainage. Although generally effective, these treatments have continued to be complicated by recurrence, especially in partially hemolyzed or septated hematomas. Recently, interest in the use of fibrinolytic agents as an adjunct to surgical treatment to address this limitation has been increasing. We conducted a systematic review, focusing on the efficacy and safety profile of fibrinolytic agents and compared the different fibrinolytic agents.
METHODS
The PubMed, EMBASE, CINAHL Plus, and Cochrane Library databases were searched for trials relevant to fibrinolytic administration in the treatment of CSDH. The findings are reported in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The data from 1702 subjects from 6 retrospective observational studies were qualitatively analyzed. In addition, we included 11 case series and reports for discussion.
RESULTS
For 1449 patients, the use of urokinase or tissue plasminogen activator improved hematoma drainage and shortened the hospital stay (7.04 days), with an overall hematoma recurrence rate of 1.59%. The incidence of infection, seizure, and intracranial bleeding was 3.18%, 0.80%, and 0.41%, respectively, which compared favorably with previously reported findings for surgical drainage without the use of fibrinolytic agents.
CONCLUSIONS
The routine use of intrathecal urokinase and tissue plasminogen activator could be a new direction in the management of CSDH. Conclusive clinical evidence is lacking, however, and further prospective controlled studies are warranted to confirm the benefit and safety of this treatment strategy and to identify the optimal agent and dosing regimen.
Topics: Chemotherapy, Adjuvant; Craniotomy; Fibrinolytic Agents; Hematoma, Subdural, Chronic; Humans; Injections, Spinal; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator
PubMed: 33722722
DOI: 10.1016/j.wneu.2021.03.029 -
Thrombosis Journal May 2024We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL. (Review)
Review
BACKGROUND
We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL.
METHODS
A systematic search for studies that assessed the association between PAI-1 4G/5G polymorphism and RPL risk published in search sources, PubMed/Medline, ISI Web of Knowledge, Scopus, and Google Scholar till January 2024 was conducted.
RESULTS
There were 23 case-control studies in total, with a high degree of statistical heterogeneity among them which indicated the need for subgroup analysis. We found a significant positive association between the risk of RPL and 4G/4G PAI-1 (OR: 2.57; 95% CI: 1.69-3.90), likewise 4G/5G (OR: 2/02 95% CI: 1.39-2.92) and mixed genotype (4G/4G+4G/5G) (OR: 2.31 95% CI: 1.81-2.93). Considering the ethnicity, the 4G/4G polymorphism is significantly associated with Asian descent (OR: 2.10; CI: 1.65-2.69) while the strong association (OR: 6.47; CI: 3.23-12.97) observed in the Greater Middle East descent is not statistically significant (P=0.16). PAI-1 4G/5G polymorphism association with RPL was only significant in Greater Middle East descent (OR: 2.93; CI: 2.41-3.56), and mixed genotype was significantly associated with RPL in Asian (OR: 2.37; CI: 1.55-3.61), Greater Middle East (OR: 3.01; CI: 2.16-4.19), and European populations (OR: 1.38; CI: 0.91-2.10). The association between RPL and PAI-1 4G/4G was significant for RPLs both under 12 weeks (OR: 1.82; 95% CI: 1.34-2.47), and under 24 weeks (OR: 1.46; 95% CI: 1.11-1.92), while considering heterozygote form the association was only significant for RPLs under 24 weeks (OR: 1.91; 95% CI: 1.58-2.31). Regarding the mixed genotype, there is a significant positive association between PAI-1 and RPL for RPLs under 12 weeks (OR: 2.09; 95% CI: 1.49-2.93), and under 24 weeks (OR: 2.10; 95% CI: 1.52-2.92).
CONCLUSIONS
Our findings indicate a significant association between the rs1799762 PAI-1 polymorphism and the risk of RPL.
PubMed: 38807142
DOI: 10.1186/s12959-024-00612-9