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The Malaysian Journal of Pathology Dec 2016Antiphospholipid syndrome (APS) is a multisystem disease that may present as venous or arterial thrombosis and/or pregnancy complications with the presence of... (Review)
Review
BACKGROUND
Antiphospholipid syndrome (APS) is a multisystem disease that may present as venous or arterial thrombosis and/or pregnancy complications with the presence of antiphospholipid antibodies. Until today, heterogeneity of pathogenic mechanism fits well with various clinical manifestations. Moreover, previous studies have indicated that genes are differentially expressed between normal and in the disease state. Hence, this study systematically searched the literature on human gene expression that was differentially expressed in Obstetric APS.
METHODOLOGY
Electronic search was performed until 31st March 2015 through PubMed and Embase databases; where the following Medical Subject Heading (MeSH) terms were used and they had been specified as the primary focus of the articles; gene, antiphospholipid, obstetric, and pregnancy in the title or abstract. From 502 studies retrieved from the search, only original publications that had performed gene expression analyses of human placental tissue that reported on differentially expressed gene in pregnancies with Obstetric APS were included. Two reviewers independently scrutinized the titles and the abstracts before examining the eligibility of studies that met the inclusion criteria. For each study; diagnostic criteria for APS, method for analysis, and the gene signature were extracted independently by two reviewers. The genes listed were further analysed with the DAVID and the KEGG pathways.
RESULTS
Three eligible gene expression studies involving obstetric APS, comprising the datasets on gene expression, were identified. All three studies showed a reduction in transcript expression on PRL, STAT5, TF, DAF, ABCA1, and HBEGF in Obstetric APS. The high enrichment score for functionality in DAVID had been positive regulation of cell proliferation. Meanwhile, pertaining to the KEGG pathway, two pathways were associated with some of the listed genes, which were ErBb signalling pathway and JAK-STAT signalling pathway.
CONCLUSION
Ultimately, studies on a genetic level have the potential to provide new insights into the regulation and to widen the basis for identification of changes in the mechanism of Obstetric APS.
Topics: Antiphospholipid Syndrome; Female; Humans; Pregnancy; Pregnancy Complications; Transcriptome
PubMed: 28028299
DOI: No ID Found -
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 -
Journal of Immunology Research 2014To evaluate the clinical associations between rheumatic fever and antiphospholipid syndrome and the impact of coexistence of these two diseases in an individual. (Review)
Review
OBJECTIVE
To evaluate the clinical associations between rheumatic fever and antiphospholipid syndrome and the impact of coexistence of these two diseases in an individual.
METHODS
Systematic review in electronics databases, regarding the period from 1983 to 2012. The keywords: "Rheumatic Fever," "Antiphospholipid Syndrome," and "Antiphospholipid Antibody Syndrome" are used.
RESULTS
were identified 11 cases described in the literature about the association of rheumatic fever and antiphospholipid syndrome. Clinical presentation of rheumatic fever was characterized by the predominance of carditis (11/11) and chorea (7/11). Regarding the manifestations of APS, the stroke was observed in 7/11 (63.6%), with one of them having probable embolic origin.
CONCLUSION
The present study brings the information that the association between APS and RF is quite rare, however, is of great clinical importance. Doctors who deal with the RF should include in their differential diagnosis the APS, especially in the presence of stroke in patients with RF and whose echocardiogram does not show intracavitary thrombi.
Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Chorea; Diagnosis, Differential; Humans; Myocarditis; Rheumatic Fever; Stroke
PubMed: 24860836
DOI: 10.1155/2014/614591 -
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 and Haemostasis Feb 2014Antibodies to prothrombin are detected by directly coating prothrombin on irradiated ELISA plates (aPT) or by using the phosphatidylserine/prothrombin complex as antigen... (Review)
Review
Antibodies to prothrombin are detected by directly coating prothrombin on irradiated ELISA plates (aPT) or by using the phosphatidylserine/prothrombin complex as antigen (aPS/PT). Although these antibodies have both been associated with antiphospholipid syndrome (APS) and a correlation between the two assays have been reported, it seems that aPT and aPS/PT belong to different populations of autoantibodies. It was our objective to systematically review the available evidence on aPT and aPS/PT antibodies and the risk of thrombosis in APS. Medline-reports published between 1988 and 2013 investigating aPT and aPS/PT as a risk factor for thrombosis were included. Whenever possible, antibody isotype(s) and site of thrombosis were analysed. This systematic review is based on available data from more than 7,000 patients and controls from 38 studies analysing aPT and 10 aPS/PT. Antibodies to prothrombin (both aPT and aPS/PT) increased the risk of thrombosis (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.72-3.5). aPS/PT seemed to represent a stronger risk factor for thrombosis, both arterial and/or venous than aPT (OR 5.11; 95%CI 4.2-6.3 and OR 1.82; 95%CI 1.44-2.75, respectively). In conclusion, routine measurement of aPS/PT (but not aPT) might be useful in establishing the thrombotic risk of patients with previous thrombosis and/or systemic lupus erythematosus. Their inclusion as laboratory criteria for the APS should be indisputably further explored.
Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Biomarkers; Humans; Odds Ratio; Phosphatidylserines; Predictive Value of Tests; Prothrombin; Risk Assessment; Risk Factors; Thrombosis
PubMed: 24172938
DOI: 10.1160/TH13-06-0509 -
Journal of Thrombosis and Haemostasis :... Jan 2014The postthrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT), occurring in 20-40% of patients. Identifying risk factors for PTS may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The postthrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT), occurring in 20-40% of patients. Identifying risk factors for PTS may be useful to provide patients with prognostic information and target prevention strategies.
OBJECTIVE
To conduct a systematic review to assess whether, among patients with DVT, inherited and acquired thrombophilias are associated with a risk of PTS.
METHODS
We searched the electronic databases PubMed, EMBASE, Scopus, and Web of Science for studies published from 1990 to 2013 that assessed any thrombophilia in adult DVT patients and its association with the development of PTS. We calculated odds ratios and 95% confidence intervals for PTS according to the presence of thrombophilia. Meta-analysis was performed using the random-effects model.
RESULTS
Sixteen studies were included: 13 assessed factor V Leiden (FVL), 10 assessed prothrombin mutation, five assessed protein S and C deficiencies, three assessed antithrombin deficiency, four assessed elevated FVIII levels, and six assessed antiphospholipid antibodies. None of the meta-analyses identified any thrombophilia to be predictive of PTS. Both FVL and prothrombin mutation appeared protective among studies including patients with both first and recurrent DVT and studies in which more than 50% of patients had an unprovoked DVT.
CONCLUSIONS
Our meta-analysis did not demonstrate a significant association between any of the thrombophilias assessed and the risk of PTS in DVT patients. Other biomarkers in the pathophysiological pathway may be more predictive of PTS.
Topics: Humans; Postthrombotic Syndrome; Thrombophilia
PubMed: 24406063
DOI: 10.1111/jth.12447 -
Medicine Mar 2016Antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are 2 rare autoimmune disorders which commonly affect women. Several previous studies showed APS... (Meta-Analysis)
Meta-Analysis Review
Impact of Antiphospholipid Syndrome and/or Systemic Lupus Erythematosus on the Long-term Adverse Cardiovascular Outcomes in Patients After Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis.
Antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are 2 rare autoimmune disorders which commonly affect women. Several previous studies showed APS to have been evolved from SLE. Secondary APS often coexists with SLE. One common feature relating these 2 diseases are the antiphospholipid antibodies, which are found in most of the patients with APS and in approximately 30% to 40% of patients with SLE, among which, about 10% develop APS. The leading cause of death in these patients is from cardiovascular disease due to accelerated atherosclerosis, which often progresses more rapidly, compared with the general population. However, the impact of APS and/or SLE on the cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI) is controversial. Therefore, to solve this issue, we aim to compare the long-term (≥1 year) adverse cardiovascular outcomes after PCI, in patients with APS and/or SLE, and those without these disorders.Medline and EMBASE databases were searched for studies comparing the long-term adverse cardiovascular outcomes between SLE and non-SLE, APS and non-APS, or SLE + APS and non-SLE + non-APS after PCI. We calculated odd ratios (OR) and 95% confidence intervals (CIs) for these categorical variables, and the pooled analyses were performed with RevMan 5.3.Seven studies consisting of a total of 253,436 patients (568 patients in the experimental group and 252,868 patients in the control group) were included in this meta-analysis. During a follow-up period of ≥1 year, mortality and myocardial Infarction (MI) were significantly higher in the experimental group (OR 2.02, 95% CI 1.63-2.49, P < 0.00001 and OR 1.59, 95% CI 1.23-2.05, P = 0.0004, respectively). Major adverse cardiac events and repeated revascularization were also significantly higher in the SLE/APS group (OR 2.40, 95% CI 1.42-4.03, P = 0.001 and OR 2.59, 95% CI 1.26-5.31, P = 0.01, respectively).Antiphospholipid syndrome and SLE are associated with significantly higher long-term (≥1 year) adverse cardiovascular outcomes after PCI. However, because of the limited number of patients and researches done, and due to a larger percentage of heterogeneity observed among several subgroups, this analysis may not generate a powerful result.
Topics: Antiphospholipid Syndrome; Cardiovascular Diseases; Humans; Lupus Erythematosus, Systemic; Percutaneous Coronary Intervention; Time Factors
PubMed: 27015221
DOI: 10.1097/MD.0000000000003200 -
Frontiers in Immunology 2022Patients with laboratory or clinical manifestations suggestive of antiphospholipid syndrome (APS) but not fulfilling the classification criteria constitute a clinical...
OBJECTIVES
Patients with laboratory or clinical manifestations suggestive of antiphospholipid syndrome (APS) but not fulfilling the classification criteria constitute a clinical challenge. This study aims to compare non-criteria APS (NC-APS) with definite APS in terms of clinical manifestations, therapies, and outcomes.
METHODS
A systematic review of observational studies comparing definite and NC-APS was performed searching four electronic databases. Data on clinical manifestations, therapies and clinical outcomes was extracted.
RESULTS
Sixteen studies, assessing a total of 3,798 participants, were included. Seven out of 10 studies found no significant difference in the prevalence of arterial or venous thrombosis between definite and NC-APS, with two studies on seronegative APS also finding no difference in thrombosis recurrence. Seven out of 12 studies found no significant difference in the prevalence of obstetric manifestations between groups, with the remaining exhibiting conflicting results. In 9 studies comparing treatment frequency in obstetric patients, all but one described similar treatment frequency, with the percentage of NC-APS treated during pregnancy ranging from 26% to 100%. In 10 studies comparing pregnancy outcomes of NC-APS versus definite APS, 7 found similar successful pregnancies/live births. Additionally, 5 studies described improvement of live births in both groups with treatment, with three signalling aspirin monotherapy as efficacious as combination therapy in NC-APS.
CONCLUSION
This review hints at an absence of marked differences in most evaluated parameters between definite and NC-APS, emphasizing the value of a more active follow-up of these patients. The low-quality available evidence highlights the need for well-defined NC-APS populations in future studies.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42020210674.
Topics: Antiphospholipid Syndrome; Aspirin; Female; Humans; Pregnancy; Pregnancy Outcome; Thrombosis; Venous Thrombosis
PubMed: 36059460
DOI: 10.3389/fimmu.2022.967178 -
Reumatologia Clinica Mar 2024This was a systematic review and meta-analysis of the prevalence of thromboembolic events in children and adolescents with antiphospholipid syndrome (APS). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
This was a systematic review and meta-analysis of the prevalence of thromboembolic events in children and adolescents with antiphospholipid syndrome (APS).
METHODS
We searched PubMed, EMBASE and Web of Science to select relevant articles published between 1 January 2000 and 27 February 2022. We used the random-effects meta-analysis to estimate pooled point prevalence rates of thromboembolic events in studies with a minimum sample size of 30.
RESULTS
We included five studies reporting data of 336 children and adolescents with primary APS and secondary APS (SAPS). Pooled point prevalence rates of initial general thrombosis, arterial thrombosis, venous thrombosis and stroke in individuals with seropositive APS were 98.2% (95% confidence interval [CI] 87.5-100), 27.6% (95% CI 21.4-34.2), 51.1% (95% CI 38.2-63.9) and 13.4% 95% CI (6.3-22.7), respectively. Pooled point prevalence rates of initial arterial and venous thromboses in children and adolescents with SAPS were 45.7% (95% CI 21.1-71.6) and 29.2% (95% CI 14.8-46), respectively.
CONCLUSION
Arterio-venous thromboembolism is highly frequent in children and adolescents with SAPS. More studies using thrombotic and non-thrombotic APS classification criteria are warranted to better assess the frequency and predictors of thromboembolism in age- and ancestry-diverse pediatric populations affected by different types of APS.
Topics: Child; Humans; Adolescent; Antiphospholipid Syndrome; Thrombosis; Venous Thrombosis; Venous Thromboembolism
PubMed: 38494306
DOI: 10.1016/j.reumae.2023.10.005 -
RMD Open Jul 2021Despite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label.
OBJECTIVE
We aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS.
METHODS
An electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology.
RESULTS
We included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA-RR 1.69, 95% CI 1.09 to 2.62, I²-24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low.
CONCLUSIONS
Current evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.
TRIAL REGISTRATION NUMBER
CRD42020216178.
Topics: Anticoagulants; Antiphospholipid Syndrome; Hemorrhage; Humans; Rivaroxaban; Vitamin K
PubMed: 34253684
DOI: 10.1136/rmdopen-2021-001678