-
Frontiers in Medicine 2023The optimal secondary thromboprophylactic strategies for patients with antiphospholipid syndrome (APS) and arterial thrombosis remain controversial. This study aimed to...
INTRODUCTION
The optimal secondary thromboprophylactic strategies for patients with antiphospholipid syndrome (APS) and arterial thrombosis remain controversial. This study aimed to evaluate the comparative efficacy and safety of various antithrombotic strategies in APS with arterial thrombosis.
METHODS
A comprehensive literature search was conducted using OVID MEDLINE, EMBASE, Web of Science, and the Cochrane Controlled Register of Trials (CENTRAL) from inception until 30 September 2022, with no language restrictions. The inclusion criteria for eligible studies were as follows: inclusion of APS patients with arterial thrombosis, treatment with either antiplatelet agents, warfarin, direct oral anticoagulants (DOACs), or a combination of these therapies, and reporting of recurrent thrombotic events.
RESULTS
We conducted a frequentist random-effects network meta-analysis (NMA) involving 13 studies with a total of 719 participants, comprising six randomized and seven non-randomized studies. In comparison to single antiplatelet therapy (SAPT), the combined use of antiplatelet and warfarin demonstrated a significant reduction in the risk of recurrent overall thrombosis, with a risk ratio (RR) of 0.41 (95% CI 0.20 to 0.85). Dual antiplatelet therapy (DAPT) showed a lower risk of recurrent arterial thrombosis compared to SAPT although the difference did not reach statistical significance, with an RR of 0.29 (95% CI 0.08 to 1.07). DOAC was associated with a significant increase in the risk of recurrent arterial thrombosis, with an RR of 4.06 (95% CI 1.33 to 12.40) when compared to SAPT. There was no significant difference in major bleeding among various antithrombotic strategies.
DISCUSSION
Based on this NMA, the combination of warfarin and antiplatelet therapy appears to be an effective approach in preventing recurrent overall thrombosis in APS patients with a history of arterial thrombosis. While DAPT may also show promise in preventing recurrent arterial thrombosis, further studies are needed to confirm its efficacy. Conversely, the use of DOACs was found to significantly increase the risk of recurrent arterial thrombosis.
PubMed: 37396906
DOI: 10.3389/fmed.2023.1196800 -
Lupus Science & Medicine Oct 2023Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterised by venous thrombosis (VT) or arterial thrombosis (AT) and/or pregnancy morbidity and the... (Meta-Analysis)
Meta-Analysis
Therapy with direct oral anticoagulants for secondary prevention of thromboembolic events in the antiphospholipid syndrome: a systematic review and meta-analysis of randomised trials.
OBJECTIVE
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterised by venous thrombosis (VT) or arterial thrombosis (AT) and/or pregnancy morbidity and the presence of antiphospholipid antibodies. Direct oral anticoagulants (DOACs) hold several advantages to vitamin K antagonists (VKAs) for prevention of thrombosis and we wish to evaluate DOACs compared with VKAs in secondary prevention of thromboembolic events in patients with APS.
METHODS
We conducted searches of the published literature using relevant data sources (MEDLINE, Embase and Cochrane CENTRAL), and of trial registers for unpublished data and ongoing trials. We included randomised trials examining individuals >18 years with APS classified according to the criteria valid when the trial was carried out. Randomised controlled trials had to examine any DOAC agent compared with any comparable drug. We tabulated all occurrences of events from all eligible randomised trials. Due to few events, ORs and 95% CIs were calculated using the Peto method.
RESULTS
5 randomised trials comprising 624 patients met the predefined eligibility criteria. The primary outcome measure was new thrombotic events, a composite endpoint of any VT or AT, during the VKA-controlled phase of treatment. According to the I inconsistency index, there was evidence of statistical heterogeneity across the studies (I=60%). Across trials, 29 and 10 thrombotic events were observed in 305 and 319 patients with APS treated with DOAC and VKA, respectively, corresponding to a combined Peto OR of 3.01 (95% CI 1.56 to 5.78, p=0.001). There was a significantly increased risk of AT while treated with DOACs compared with VKA (OR 5.5 (2.5, 12.1) p<0.0001), but no difference in the risk of VT (p=0.87). We found no significant difference in risk of bleeding.
CONCLUSIONS
DOACs were associated with a significant increase in the risk of a new thrombotic event, especially AT, favouring standard prophylaxis with warfarin.
PROSPERO REGISTRATION NUMBER
CRD42019126720.
Topics: Humans; Antiphospholipid Syndrome; Secondary Prevention; Lupus Erythematosus, Systemic; Anticoagulants; Thrombosis; Randomized Controlled Trials as Topic
PubMed: 37899090
DOI: 10.1136/lupus-2023-001018 -
The Malaysian Journal of Pathology Dec 2016Antiphospholipid antibodies (aPL) are autoantibodies that attack phospholipid through anti-beta 2-glycoprotein 1. The actions of aPL are associated with events leading... (Review)
Review
INTRODUCTION
Antiphospholipid antibodies (aPL) are autoantibodies that attack phospholipid through anti-beta 2-glycoprotein 1. The actions of aPL are associated with events leading to thrombosis and morbidity in pregnancy. Antiphospholipid syndrome (APS) is diagnosed when a patient is persistently positive for aPL and also has recognised clinical manifestations such as recurrent pregnancy losses, arterial or venous thrombosis and in a catastrophic case, can result in death. Unfortunately, the pathogenesis of APS is still not well established. Recently, microRNA expressed in many types of diseased tissues were claimed to be involved in the pathological progression of diseases and has become a useful biomarker to indicate diseases, including APS.
OBJECTIVE
This systematic review aims to search for research papers that are focussing on microRNA expression profiles in APS.
METHOD
Three search engines (Ebcohost, ProQuest and Ovid) were used to identify papers related to expression of specific microRNA in antiphospholipid syndrome.
RESULTS AND DISCUSSION
A total of 357 papers were found and screened, out of which only one study fulfilled the requirement. In this particular study blood samples from APS patients were tested. The microRNAs found to be related to APS were miR-19b and miR-20a. No data was found on specific microRNA being expressed in obstetric antiphospholipid syndrome. Analysis on the microRNA target genes revealed that most genes targeted by miR-19b and miR-20a involve in TGF-Beta Signalling and VEGF, hypoxia and angiogenesis pathways.
CONCLUSION
In view of the limited data on the expressions of microRNA in APS we recommend further research into this field. Characterization of microRNA profile in blood as well as in placenta tissue of patients with APS could be useful in identifying microRNAs involved in obstetric APS.
Topics: Antiphospholipid Syndrome; Humans; MicroRNAs
PubMed: 28028298
DOI: No ID Found -
BMJ Clinical Evidence Feb 2011Recurrent miscarriage is the spontaneous loss of three or more consecutive pregnancies with the same biological father in the first trimester, and affects 1% to 2% of... (Review)
Review
INTRODUCTION
Recurrent miscarriage is the spontaneous loss of three or more consecutive pregnancies with the same biological father in the first trimester, and affects 1% to 2% of women, half of whom have no identifiable cause. Overall, 75% of affected women will have a successful subsequent pregnancy, but this rate falls for older mothers and with increasing number of miscarriages. Antiphospholipid syndrome, with anticardiolipin or lupus anticoagulant antibodies, is present in 15% of women with recurrent first and second trimester miscarriage.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for unexplained recurrent miscarriage? What are the effects of treatments for recurrent miscarriage caused by antiphospholipid syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aspirin (low dose), bed-rest, corticosteroids, early scanning in subsequent pregnancies, heparin plus low-dose aspirin, human chorionic gonadotrophin, intravenous immunoglobulin treatment, lifestyle adaptation, oestrogen, paternal white cell immunisation, progesterone, trophoblastic membrane infusion, and vitamin supplementation.
Topics: Abortion, Habitual; Anti-Inflammatory Agents, Non-Steroidal; Antiphospholipid Syndrome; Aspirin; Heparin; Humans
PubMed: 21718553
DOI: No ID Found -
Human Reproduction Update Apr 2020Recurrent pregnancy loss (RPL) occurs in 1-3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recurrent pregnancy loss (RPL) occurs in 1-3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses.
OBJECTIVE AND RATIONALE
The aim of this systematic review was to evaluate the current evidence on the prevalence of abnormal test results for RPL amongst patients with two versus three or more pregnancy losses. We also aimed to contribute to the debate regarding whether the investigations for RPL should take place after two or three or more pregnancy losses.
SEARCH METHODS
Relevant studies were identified by a systematic search in OVID Medline and EMBASE from inception to March 2019. A search for RPL was combined with a broad search for terms indicative of number of pregnancy losses, screening/testing for pregnancy loss or the prevalence of known risk factors. Meta-analyses were performed in case of adequate clinical and statistical homogeneity. The quality of the studies was assessed using the Newcastle-Ottawa scale.
OUTCOMES
From a total of 1985 identified publications, 21 were included in this systematic review and 19 were suitable for meta-analyses. For uterine abnormalities (seven studies, odds ratio (OR) 1.00, 95% CI 0.79-1.27, I2 = 0%) and for antiphospholipid syndrome (three studies, OR 1.04, 95% CI 0.86-1.25, I2 = 0%) we found low quality evidence for a lack of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses. We found insufficient evidence of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses for chromosomal abnormalities (10 studies, OR 0.78, 95% CI 0.55-1.10), inherited thrombophilia (five studies) and thyroid disorders (two studies, OR 0.52, 95% CI: 0.06-4.56).
WIDER IMPLICATIONS
A difference in prevalence in uterine abnormalities and antiphospholipid syndrome is unlikely in women with two versus three pregnancy losses. We cannot exclude a difference in prevalence of chromosomal abnormalities, inherited thrombophilia and thyroid disorders following testing after two versus three pregnancy losses. The results of this systematic review may support investigations after two pregnancy losses in couples with RPL, but it should be stressed that additional studies of the prognostic value of test results used in the RPL population are urgently needed. An evidenced-based treatment is not currently available in the majority of cases when abnormal test results are present.
Topics: Abortion, Habitual; Antiphospholipid Syndrome; Chromosome Aberrations; Female; Fertilization; Humans; Pregnancy; Risk Factors; Thrombophilia; Thyroid Diseases; Urogenital Abnormalities; Uterus
PubMed: 32103270
DOI: 10.1093/humupd/dmz048 -
Journal of Clinical Medicine Jan 2023Hydroxychloroquine (HCQ) has been used in the treatment of systematic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), but its effect on lupus activity... (Review)
Review
Effect of Hydroxychloroquine on Lupus Activity, Preeclampsia and Intrauterine Growth Restriction in Pregnant Women with Systemic Lupus Erythematosus and/or Antiphospholipid Syndrome: A Systematic Review and Meta-Analysis.
BACKGROUND
Hydroxychloroquine (HCQ) has been used in the treatment of systematic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), but its effect on lupus activity during pregnancy, preeclampsia and intrauterine growth restriction (IUGR) remains unclear.
METHODS
PubMed, Embase and Cochrane databases were searched before 11 September 2022 for randomized clinical trials (RCT) or observational studies involving additional HCQ treatment and pregnant women diagnosed as having SLE and/or APS/positive antiphospholipid antibodies (aPLs). Risks of high lupus activity, preeclampsia and IUGR were explored.
RESULTS
One RCT and 13 cohort studies were included. A total of 1764 pregnancies were included in the pooled meta-analysis (709 in the HCQ group vs. 1055 in the control group). After the additional use of HCQ, the risk of high lupus activity decreased (RR: 0.74, 95% CI: 0.57-0.97, = 0.03). For preeclampsia, the total incidence decreased (RR: 0.54, 95% CI: 0.37-0.78, = 0.001). The subgroup analysis showed statistical significance in the SLE subgroup (RR: 0.51, 95% CI: 0.34-0.78, = 0.002) but not in the APS/aPLs subgroup (RR: 0.66, 95% CI: 0.29-1.54, = 0.34). For IUGR, the decrease in incidence was not statistically significant (RR: 0.80, 95% CI: 0.47-1.35, = 0.46), neither in the SLE subgroup (RR: 0.74, 95% CI: 0.40-1.36, = 0.33) nor in the APS/aPLs subgroup (RR: 1.26, 95% CI: 0.34-4.61, = 0.73).
CONCLUSION
The additional use of HCQ may decrease the risk of high lupus activity during pregnancy and the incidence of preeclampsia for SLE patients, but the results do not support that using HCQ decreases the incidence of preeclampsia for APS/aPLs patients or reduces IUGR risk for SLE and/or APS/aPLs patients.
PubMed: 36675415
DOI: 10.3390/jcm12020485 -
Rheumatology (Oxford, England) Dec 2021Cognitive dysfunction is common in patients with aPL (including primary APS or APS associated with SLE). Neuroimaging biomarkers may contribute to our understanding of...
OBJECTIVES
Cognitive dysfunction is common in patients with aPL (including primary APS or APS associated with SLE). Neuroimaging biomarkers may contribute to our understanding of mechanisms of cognitive dysfunction in these cohorts. This review aimed to investigate: (i) the prevalence of cognitive dysfunction in studies including neuroimaging biomarkers; and (ii) associations between cognition and neuroimaging biomarkers in patients with APS/aPL.
METHODS
We conducted a systematic search of electronic databases PubMed, Science Direct, Scopus and PsycINFO, and included studies with descriptions of neuroimaging findings, cognitive dysfunction or both, in patients with aPL positivity (LA, IgG and IgM aCL and anti-β2 glycoprotein-I antibodies).
RESULTS
Of 120 search results we included 20 eligible studies (6 APS, 4 SLE with APS/aPL and 10 NPSLE). We identified a medium risk of bias in 6/11 (54%) of cohort studies and 44% of case-control studies, as well as marked heterogeneity in cognitive assessment batteries, APS and aPL definitions, and neuroimaging modalities and protocols. The prevalence of cognitive dysfunction ranged between 11 and 60.5%. Structural MRI was the most common imaging modality, reporting cognitive dysfunction to be associated with white matter hyperintensities, ischaemic lesions and cortical atrophy (four with cerebral atrophy, two with white matter hyperintensities and two with cerebral infarcts).
CONCLUSION
Our findings confirm that cognitive impairment is commonly found in patients with aPL (including APS, SLE and NPSLE). The risk of bias, and heterogeneity in the cognitive and neuroimaging biomarkers reported does not allow for definitive conclusions.
Topics: Antiphospholipid Syndrome; Biomarkers; Cognition; Cognitive Dysfunction; Dementia; Humans; Neuroimaging; Prevalence
PubMed: 34003972
DOI: 10.1093/rheumatology/keab452 -
BMJ Clinical Evidence Apr 2008Recurrent miscarriage is the spontaneous loss of three or more consecutive pregnancies with the same biological father in the first trimester, and affects 1-2% of women,... (Review)
Review
INTRODUCTION
Recurrent miscarriage is the spontaneous loss of three or more consecutive pregnancies with the same biological father in the first trimester, and affects 1-2% of women, half of whom have no identifiable cause. Overall, 75% of affected women will have a successful subsequent pregnancy, but this rate falls for older mothers and with increasing number of miscarriages. Antiphospholipid syndrome, with anticardiolipin or lupus anticoagulant antibodies, is present in 15% of women with recurrent first and second trimester miscarriage.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for unexplained recurrent miscarriage? What are the effects of treatments for recurrent miscarriage caused by antiphospholipid syndrome? We searched: Medline, Embase, The Cochrane Library and other important databases up to April 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aspirin (low dose), bed rest, corticosteroids, early scanning in subsequent pregnancies, heparin plus low-dose aspirin, human chorionic gonadotrophin, intravenous immunoglobulin treatment, lifestyle adaptation, oestrogen, paternal white cell immunisation, progesterone, trophoblastic membrane infusion, and vitamin supplementation.
Topics: Abortion, Habitual; Anti-Inflammatory Agents, Non-Steroidal; Antiphospholipid Syndrome; Aspirin; Heparin; Humans
PubMed: 19450314
DOI: No ID Found -
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 -
International Journal of Molecular... Jun 2020The relationship between antiphospholipid antibodies (aPL) and autoimmune haemolytic anaemia (AIHA) has never been systematically addressed. The aim of this study is to... (Meta-Analysis)
Meta-Analysis Review
The relationship between antiphospholipid antibodies (aPL) and autoimmune haemolytic anaemia (AIHA) has never been systematically addressed. The aim of this study is to assess the link between aPL and AIHA in adult systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). This study performed an EMBASE/PubMed search from inception to June 2019 and meta-analysis using Peto's odds ratios. The pooled prevalence (PP) of IgG/IgM anticardiolipin (aCL) and lupus anticoagulant (LA) was greater in AIHA +ve than AIHA -ve patients (34.7% vs. 27.6%, = 0.03; 33.3% vs. 21.8%, < 0.0001; 20.9% vs. 8.3%, = 0.01). The PP of AIHA was greater in: (1) IgG and IgM aCL +ve than -ve patients (21.8% vs. 11.1%, = 0.001 and 18.7% vs. 6.3%, < 0.0001), (2) in SLE related APS than in primary APS patients (22.8% vs. 3.9% < 0.0001), (3) in APS +ve than APS -ve SLE patients (23.2% vs. 8.4%, = 0.01), and (4) in thrombotic APS than non-thrombotic APS/SLE patients (26.8% vs. 10%, = 0.03). The PP of IgG/IgM aCL and LA was greater in DAT +ve than DAT -ve patients (42.4% vs. 12.8%, < 0.0001; 26.2% vs. 12.8%, = 0.03 and 29.2% vs. 15.7%, = 0.004 respectively). It was found that AIHA prevalence is maximal in SLE with aPL/APS, low-moderate in SLE without aPL and minimal in PAPS. Moreover, AIHA is rightly included among the classification criteria for SLE but not for APS/aPL. The significance of an isolated DAT positivity remains unclear in this setting.
Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Coombs Test; Humans; Lupus Erythematosus, Systemic; Thrombosis
PubMed: 32527000
DOI: 10.3390/ijms21114120