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Annals of Medicine and Surgery (2012) Jul 2023Optimal treatment regimen for patients with antiphospholipid syndrome (APS) remain unclear. Therefore, the authors sought to compare the outcomes of vitamin K...
UNLABELLED
Optimal treatment regimen for patients with antiphospholipid syndrome (APS) remain unclear. Therefore, the authors sought to compare the outcomes of vitamin K antagonists (VKAs) vs. direct oral anticoagulants (DOACs) in patients with APS.
METHODS
MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials comparing efficacy and safety of VKAs and DOACs inhibitors in patients with APS. Recurrent thrombosis, all-cause mortality, stroke, adverse reactions, and bleeding were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs.
RESULTS
The analysis included 625 patients from four randomized controlled trials and one post hoc analysis. Meta-analysis showed statistically non-significant difference between DOACs inhibitors and VKAs in the recurrent thrombosis risk (arterial or venous) [RR 2.77 (95%, CI 0.79, 9.65); =0.11, I=50%]. Consistent results were revealed among patients with the previous history of arterial thrombosis [RR 2.76 (95% CI 0.93, 8.16); =0.75, I=0%], venous thrombosis [RR 1.71 (95% CI 0.60, 4.84); =0.31, I=15%] and patients who were triple antiphospholipid positive [RR 4.12 (95% CI 0.46, 37.10); =0.21, I=58%]. DOACs inhibitors were significantly associated with increased risk of stroke [RR 8.51 (95% CI 2.35, 3.82); =0.47, I=0%].
CONCLUSION
DOACs exhibited increased risk of stroke among patients with APS. In addition, although not significant, the higher RRs among patients on DOACs may indicate higher risk of thrombotic events associated with DOACs.
PubMed: 37427194
DOI: 10.1097/MS9.0000000000000903 -
Autoimmunity Reviews Oct 2022Microvascular renal lesions have been described in patients with antiphospholipid antibodies (aPL), however their association with aPL is inconsistent among studies.... (Meta-Analysis)
Meta-Analysis Review
Increased risk of acute and chronic microvascular renal lesions associated with antiphospholipid antibodies in patients with systemic lupus erythematosus: A systematic review and meta-analysis.
BACKGROUND
Microvascular renal lesions have been described in patients with antiphospholipid antibodies (aPL), however their association with aPL is inconsistent among studies. Therefore, our objective was to investigate associations between microvascular renal lesions and aPL among systemic lupus erythematosus (SLE) patients.
METHODS
Studies were selected if they included SLE patients with and without aPL positivity with a description of kidney biopsy identifying acute and/or chronic microvascular renal lesions as well as lupus nephritis. Data sources were Pubmed, Embase, Cochrane Library, hand search, congress abstracts, and reference lists of studies, without language restrictions. Risk estimates were independently extracted by 2 investigators. Pooled effect estimates were obtained by using the Mantel-Haenszel method (random effects).
RESULTS
Of 1860 identified records obtained between 1991 and 2021, 35 published studies (10 cohorts, 7 case-control, 18 cross-sectional) met inclusion criteria, including 3035 SLE patients according to American College of Rheumatology criteria and 454 cases of microvascular renal lesions. Frequency of microvascular renal lesions in aPL-positive vs. aPL-negative SLE patients was 31.3% vs. 10.4%, respectively. The overall pooled odds ratios (OR) for microvascular renal lesions in aPL-positive vs. aPL-negative SLE patients was 3.03 (95% confidence interval [CI], 2.25-4.09). The risk of microvascular renal lesions was the highest for lupus anticoagulant (OR = 4.84 [95% CI, 2.93 to 8.02]) and IgG anticardiolipin antibodies (OR = 3.12 [95% CI,1.08-9.02]) while the association with anti-β-glycoprotein I antibodies (OR = 1.88 [95% CI, 0.25-14.14]) did not reach statistical significance. Furthermore, aPL were not associated with any classes of lupus nephritis.
CONCLUSION
In SLE patients, aPL-positivity is associated with a significant 3- to 5-fold increased risk for specific microvascular renal lesions. This risk is mainly driven by lupus anticoagulant and IgG anticardiolipin antibodies. Our results support the inclusion of microvascular renal lesions as new criteria for definite antiphospholipid syndrome.
Topics: Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Cross-Sectional Studies; Glycoproteins; Humans; Immunoglobulin G; Kidney; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Lupus Nephritis
PubMed: 35907609
DOI: 10.1016/j.autrev.2022.103158 -
Rheumatology and Therapy Feb 2023The objective of this work was to conduct a systematic literature review (SLR) and meta-analysis (MA) to evaluate the relative risk (RR) of venous thromboembolism (VTE)... (Review)
Review
The objective of this work was to conduct a systematic literature review (SLR) and meta-analysis (MA) to evaluate the relative risk (RR) of venous thromboembolism (VTE) events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients with systemic lupus erythematosus (SLE) compared with patients without SLE, as well as the absolute risk (AR) (measured by incidence proportion) and incidence rate (IR) of VTE events in patients with SLE. The SLR was conducted using Embase, MEDLINE, and MEDLINE In-Process to identify observational studies evaluating the risk of VTE, DVT, and PE events in adult patients with SLE compared with the general population, published January 2000 to September 2020. Random-effects models were used as the primary approach in the MA. Heterogeneity was assessed on the basis of the I value. Sensitivity analyses were performed to assess the robustness of results to various conditions, and subgroup analysis was performed for the AR of VTE by antiphospholipid status (aPLs) and antiphospholipid syndrome (APS). Of the 50 publications included for data extraction, 44 contained data for consideration in the MA of any one of the measures of interest (RR, AR, or IR) for VTE, DVT, or PE. The pooled RR indicates statistically significantly higher risk of VTE (RR 4.38, 95% confidence interval 2.63-7.29) in patients with SLE compared with the general population. Considerable heterogeneity was present in nearly all MA (I = 75-100%). Moreover, a higher pooled AR of VTE was estimated in patients with SLE with aPLs (n/N = 0.13) and APS (n/N = 0.63) compared with patients with SLE without aPLs/APS (n/N = 0.07). Overall, there was evidence of an increased risk of VTE, DVT, and PE in patients with SLE compared with the general population.
PubMed: 36471199
DOI: 10.1007/s40744-022-00513-1 -
Autoimmunity Reviews Mar 2018Antiphospholipid Syndrome (APS) is an autoimmune multifactorial disorder. Genetics is believed to play a contributory role in the pathogenesis of APS, especially in... (Review)
Review
BACKGROUND
Antiphospholipid Syndrome (APS) is an autoimmune multifactorial disorder. Genetics is believed to play a contributory role in the pathogenesis of APS, especially in thrombosis development and pregnancy morbidity. In the last 20 years, extensive research on genetic contribution on APS indicates that APS is a polygenic disorder, where a number of genes are involved in the development of its clinical manifestations.
AIMS
The aim of this systematic review is to evaluate the genetic risk factors in thrombotic primary APS. Additionally, to assess the common molecular functions, biological processes, pathways, interrelations with the gene encoded proteins and RNA-Seq-derived expression patterns over different organs of the associated genes via bioinformatic analyses.
METHODS
Without restricting the year, a systematic search of English articles was conducted (up to 4th September 2017) using Web of Science, PubMed, Scopus, ScienceDirect and Google Scholar databases. Eligible studies were selected based on the inclusion criteria. Two researchers independently extracted the data from the included studies. Quality assessment of the included studies was carried out using a modified New-Castle Ottawa scale (NOS).
RESULTS
From an initial search result of 2673 articles, 22 studies were included (1268 primary APS patients and 1649 healthy controls). Twenty-two genes were identified in which 16 were significantly associated with thrombosis in primary APS whereas six genes showed no significant association with thrombosis. Based on the NOS, 14 studies were of high quality while 6 were low quality studies. From the bioinformatic analyses, thrombin-activated receptor activity (q = 6.77 × 10), blood coagulation (q = 2.63 × 10), formation of fibrin clot (q = 9.76 × 10) were the top hit for molecular function, biological process and pathway categories, respectively. With the highest confidence interaction score of 0.900, all of the thrombosis-associated gene encoded proteins of APS were found to be interconnected except for two. Based on the pathway analysis, cumulatively all the genes affect haemostasis [false discovery rate (FDR) = 1.01 × 10] and the immune system [FDR = 9.93 × 10]. Gene expression analysis from RNA-Seq data revealed that almost all the genes were expressed in 32 different tissues in the human body.
CONCLUSION
According to our systematic review, 16 genes contribute significantly in patients with thrombotic primary APS when compared with controls. Bioinformatic analyses of these genes revealed their molecular interconnectivity in protein levels largely by affecting blood coagulation and immune system. These genes are expressed in 32 different organs and may pose higher risk of developing thrombosis anywhere in the body of primary APS patients.
Topics: Antiphospholipid Syndrome; Case-Control Studies; Computational Biology; Female; Humans; Male; Pregnancy; Prospective Studies; Risk Factors
PubMed: 29355608
DOI: 10.1016/j.autrev.2017.10.014 -
Cureus Sep 2022Due to a high risk of recurrent thromboembolism in patients with antiphospholipid syndrome (APS), long-term anticoagulation is recommended. For decades, vitamin K... (Review)
Review
Due to a high risk of recurrent thromboembolism in patients with antiphospholipid syndrome (APS), long-term anticoagulation is recommended. For decades, vitamin K antagonists (VKAs) have been the gold standard for thromboprophylaxis in these patients. Due to the widespread use of direct oral anticoagulants (DOACs) in various thromboembolic conditions and their potential advantages compared to VKAs, several studies have been conducted to evaluate their safety and efficacy in APS. We performed a literature search using PubMed, Embase, and Cochrane databases for studies comparing DOACs to VKAs in patients with APS. Relative risk (RR) and the corresponding 95% confidence intervals (95% CI) were estimated for recurrent thromboembolic events, bleeding, and mortality. A total of 1437 patients pooled from 12 studies were analyzed. The risk of recurrent thrombosis, especially arterial thrombosis, doubled with DOACs compared to VKAs (RR 2.61, 95% CI 1.44-4.71; p=0.001). The risk further increased in patients with a triple-positive antiphospholipid antibody profile (RR 4.50, 95% CI 1.91-10.63; p=0.0006) and with the use of rivaroxaban (RR 1.95, 95% CI 1.10-3.45; p=0.02). The risk of major bleeding and mortality were not significantly different between the two arms. A trend favoring DOACs compared to VKAs was observed for all bleeding events. This meta-analysis comes in agreement with previous studies and supports the use of VKAs in APS. Our study revealed that VKAs remain the gold standard for the management of APS, especially triple-positive APS. DOACs, particularly rivaroxaban, are not as effective in preventing recurrent thromboembolism in high-risk APS patients. Further studies are needed to evaluate the role of DOACs apart from rivaroxaban with a focus on their efficacy in the management of isolated or double-positive APS.
PubMed: 36299971
DOI: 10.7759/cureus.29449 -
Seminars in Arthritis and Rheumatism Dec 2020To evaluate the clinical relevance of antiphospholipid antibodies (aPL) in patients with lower extremity peripheral artery disease (PAD). (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the clinical relevance of antiphospholipid antibodies (aPL) in patients with lower extremity peripheral artery disease (PAD).
DATA SOURCES
EMBASE and MEDLINE databases were searched from inception to March 2020 for clinical studies reporting on the association between of aPL [IgG/IgM anticardiolipin (aCL) and lupus anticoagulant (LA)] and PAD.
METHODS
We determined the pooled prevalence (PP) of patients positive for aPL in PAD or the PP of PAD in patients positive for aPL; we employed Peto's odds ratio with random effect for the meta-analysis.
RESULTS
Twenty-one studies comprising 6,057 patients were evaluated: in patients with PAD, the PP of IgG aCL was 12% vs 4.1% in those without, IgM aCL was 13.2% vs 2.1%, and LA 13.3% vs 3.3%, respectively. The PP of patients with LA was greater in critical limb ischemia than in the control group (19.3% vs 4.2%). Also, the PP of patients with LA was greater in the failed than in the successful revascularisation group (35.8% vs 15.8%). The PP of post-procedural revascularisation failures was similar in the groups given or not given oral anticoagulation (59.2% vs 61.9%).
CONCLUSION
All the aPL related to PAD regardless of diagnostic definition used, whereas LA related also to critical limb ischaemia and failed revascularisation. Data expressed as percentage of participants positive for aPL limit the interpretation of these relationships.
Topics: Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Humans; Lower Extremity; Lupus Coagulation Inhibitor; Peripheral Arterial Disease
PubMed: 33065424
DOI: 10.1016/j.semarthrit.2020.08.012 -
Autoimmunity Reviews May 2017Hematopoietic stem cell transplantation (HSCT) has been proposed as a therapeutic option for patients with Systemic Lupus Erythematosus (SLE) refractory to standard... (Review)
Review
BACKGROUND
Hematopoietic stem cell transplantation (HSCT) has been proposed as a therapeutic option for patients with Systemic Lupus Erythematosus (SLE) refractory to standard therapy. This therapeutic approach has been applied to other severe autoimmune diseases refractory to standard therapy with promising results.
AIM
To systematically review the literature and analyze the available evidence on HSCT therapy in patients with SLE and antiphospholipid syndrome (APS), with a focus on therapy efficacy and occurrence of adverse events.
METHODS
A detailed literature search, applied to Ovid MEDLINE, In-Process and Other Non-Indexed Citation and Ovid Medline 1986 to 2014, has been developed a priori to identify articles that reported findings from clinical and laboratory studies that investigated the effect of HCT in patients with SLE.
RESULTS
Twenty-five studies met all inclusion criteria, including a total of 279 SLE patients; of those, 54 patients also fulfilled the classification criteria of APS. The majority of the studies reported an improvement after HSCT in terms of diseases activity control (assessed with SLEDAI, or time-free from diseases) or overall survival. However, one study reported no net benefit of HSCT when compared to immunosuppression alone. One retrospective study reported an overall survival at 5years of 81% in 28 SLE patients. Of note, 5 cases (9.3%) of aPL negativization were reported after HSCT in the APS patients. When combining these studies and analyzing these patients with APS, 32 out of 44 (73%) were able to discontinue anticoagulation after HSCT. Our findings also demonstrate a total of 86 infections in the pool of patients (30.8%), 3 of which resulted in the death of the patient (1.3%). We observed an annual incidence of infection of 11.9% with a mean follow up of 36.2months.
CONCLUSION
Preliminary results of HSCT as a therapeutic option for SLE appear promising. Further studies are warranted in order to assess the safety of the procedure for both the occurrence of secondary autoimmune disease and the rate of infection. However, the rate of adverse effects confines this option to very selected cases of SLE patients resistant or refractory to standard approaches.
Topics: Adult; Antiphospholipid Syndrome; Female; Hematopoietic Stem Cell Transplantation; Humans; Lupus Erythematosus, Systemic; Male; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous; Young Adult
PubMed: 28279836
DOI: 10.1016/j.autrev.2017.03.008 -
Thrombosis Research Jun 2022Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) and thrombotic events. The association of... (Meta-Analysis)
Meta-Analysis Review
Prevalence of aPhosphatidylserine/prothrombin antibodies and association with antiphospholipid antibody profiles in patients with antiphospholipid syndrome: A systematic review and meta-analysis.
BACKGROUND
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) and thrombotic events. The association of aPLs with thrombotic events depends on the number of positive tests. Besides the three classical tests to classify APS, phosphatidylserine/prothrombin complex autoantibodies (aPS/PT) are increasingly used to better define this condition. The aim of this systematic review was to evaluate the prevalence of aPS/PT in general and according to antiphospholipid antibody profiles in patients with APS.
METHODS
A systematic search of PubMed, Web of Science, and the Cochrane Library from January 1990 to September 2021 was carried out according to PRISMA guidelines. Proportions and 95% confidence intervals (CIs) were calculated using random-effects model. Publication biases were evaluated via visualization of funnel plots along with Egger's and Begg's tests.
RESULTS
Twenty-one articles about the prevalence of aPS/PT in 1853 patients with APS were deemed eligible and analyzed according to the inclusion criteria. Pooled prevalence of aPS/PT IgG alone, IgM alone, and IgG/M were 50.0%, 45.0%, and 65.0%, respectively. No significant publication bias was detected from funnel plots or Egger's and Begg's tests. When the prevalence of aPS/PT was calculated in homogeneous aPLs, a much higher rate of pooled prevalence of aPS/PT IgG/M in patients positive for Lupus Anticoagulant (84.5%) and in those with triple positivity (83.4%) was found.
CONCLUSIONS
These data show a high rate of aPS/PT positivity in patients with APS (especially in those positive for LAC) but further studies are needed to ascertain whether this test might be useful in the laboratory classification criteria of APS.
Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Humans; Immunoglobulin G; Phosphatidylserines; Prevalence; Prothrombin; Thrombosis
PubMed: 35526513
DOI: 10.1016/j.thromres.2022.04.021 -
Current Problems in Cardiology Jun 2023Currently, the guidelines for the prevention of atherosclerosis in patients with antiphospholipid syndrome (APS) do not differ substantially from those in the general... (Meta-Analysis)
Meta-Analysis Review
Risk of Subclinical Atherosclerosis in Patients with Antiphospholipid Syndrome and Subjects With Antiphospholipid Antibody Positivity: A Systematic Review and Meta-analysis.
Currently, the guidelines for the prevention of atherosclerosis in patients with antiphospholipid syndrome (APS) do not differ substantially from those in the general population. We aimed to assess the risk of subclinical atherosclerosis in patients with APS and subjects with antiphospholipid antibody (aPL) positivity. Systematic literature search was conducted through Medline and Scopus until January 2023. Random effects meta-analyses were performed to examine the differences in markers of subclinical atherosclerosis between APS patients, subjects positive for aPLs and healthy controls. Patients with APS had significantly higher values of common carotid artery (CCA) intima-media thickness (IMT) (MD = 0.07 mm; P < 0.0001), internal carotid artery IMT (MD = 0.06 mm; P < 0.01), carotid bifurcation IMT (MD = 0.14 mm; P < 0.01) and were more frequently diagnosed with atherosclerotic plaques compared to controls (OR = 3.73; P < 0.01). Similarly, APS patients showed a decreased flow and nitrate-mediated dilation (MD = -4.52 %; <0.01, MD = -1.25 %; P < 0.05, respectively). Interestingly, comparable were the results for subjects with aPL positivity, who had higher CCA-IMT (MD = 0.06 mm; P < 0.01) and higher prevalence of atherosclerotic plaques (OR = 2.59; P = 0.08) compared to controls. Sensitivity analysis conducted on primary APS patients revealed that the risk of atherosclerosis is associated with APS per se and is not exclusively driven by other underlying conditions. Patients with APS and subjects with aPLs have an increased risk of subclinical atherosclerosis and require early and disease-specific prevention of atherosclerosis.
Topics: Humans; Antiphospholipid Syndrome; Plaque, Atherosclerotic; Carotid Intima-Media Thickness; Atherosclerosis; Antibodies, Antiphospholipid; Risk Factors
PubMed: 36841314
DOI: 10.1016/j.cpcardiol.2023.101672 -
Survey of Ophthalmology 2016Systemic lupus erythematosus (SLE) is a life-threatening multisystem inflammatory condition that may affect almost any part of the eye. We provide an update for the... (Review)
Review
Systemic lupus erythematosus (SLE) is a life-threatening multisystem inflammatory condition that may affect almost any part of the eye. We provide an update for the practicing ophthalmologist comprising a systematic review of the recent literature presented in the context of current knowledge of the pathogenesis, diagnosis, and treatment of this condition. We review recent advances in the understanding of the influence of genetic and environmental factors on the development of SLE. Recent changes in the diagnostic criteria for SLE are considered. We assess the potential for novel molecular biomarkers to find a clinical application in disease diagnosis and stratification and in the development of therapeutic agents. We discuss limited forms of SLE and their differentiation from other collagen vascular disorders and review recent evidence underlying the use of established and novel therapeutics in this condition, including specific implications regarding monitoring for ocular toxicity associated with antimalarials.
Topics: Antiphospholipid Syndrome; Eye Diseases; Humans; Keratoconjunctivitis Sicca; Lupus Erythematosus, Systemic; Ophthalmology; Retinal Diseases; Sjogren's Syndrome
PubMed: 26197421
DOI: 10.1016/j.survophthal.2015.06.003