-
Medicina Clinica Jul 2023The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid... (Review)
Review
The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid syndrome (APS). We searched for clinical trials, cohort studies and meta-analyses published from January 1, 2012 to September 30, 2022. Articles that analyzed the efficacy of DOAC in the prevention of thrombosis recurrence, with or without comparison with antivitamin K (VKA) drugs, were selected. DOACs, specifically rivaroxaban and apixaban, were significantly less effective than VKAs in preventing recurrence of thrombosis in patients with APS and prior arterial thrombosis or the concomitant presence of two or three different antiphospholipid antibodies. The proportion of patients with severe bleeding as side effect are similar in those treated with DOAC and with VKA. The results argue against the use of DOAC in the treatment of patients with thrombotic APS.
Topics: Humans; Antiphospholipid Syndrome; Anticoagulants; Factor Xa Inhibitors; Warfarin; Thrombosis; Administration, Oral
PubMed: 37105842
DOI: 10.1016/j.medcli.2023.03.011 -
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the published literature using relevant data sources (MEDLINE, Embase and Cochrane CENTRAL), and of trial registers for unpublished data and ongoing trials.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 -
Clinical Immunology (Orlando, Fla.) Nov 2023Antiphospholipid syndrome (APS) is a systemic autoimmune disease clinically associated with thrombotic and obstetric events. Additional manifestations have been...
Clinical features, risk factors, and outcomes of diffuse alveolar hemorrhage in antiphospholipid syndrome: A mixed-method approach combining a multicenter cohort with a systematic literature review.
BACKGROUND
Antiphospholipid syndrome (APS) is a systemic autoimmune disease clinically associated with thrombotic and obstetric events. Additional manifestations have been associated with APS, like diffuse alveolar hemorrhage (DAH). We aimed to summarize all the evidence available to describe the presenting clinical features, their prognostic factors, and short- and long-term outcomes.
METHODS
We performed a mixed-method approach combining a multicenter cohort with a systematic literature review (SLR) of patients with incident APS-associated DAH. We described their clinical features, treatments, prognostic factors, and outcomes (relapse, mortality, and requirement of mechanical ventilation [MV]). Kaplan-Meier methods were used to estimate relapse and mortality rates, and Cox and logistic regression models were used to assess the factors associated as appropriate.
RESULTS
We included 219 patients with incident APS-associated DAH (61 from Mayo Clinic and 158 from SLR). The median age was 39.5 years, 51% were female, 29% had systemic lupus erythematosus, and 34% presented with catastrophic APS (CAPS). 74% of patients had a history of thrombotic events, and 26% of women had a history of pregnancy morbidity; half of the patients had a history of thrombocytopenia, and a third had valvulopathy. Before DAH, 55% of the patients were anticoagulated. At DAH onset, 65% of patients presented hemoptysis. The relapse rate was 47% at six months and 52% at one year. Triple positivity (HR 4.22, 95% CI 1.14-15.59) was associated with relapse at six months. The estimated mortality at one and five years was 30.3% and 45.8%. Factors associated with mortality were severe thrombocytopenia (< 50 K/μL) (HR 3.10, 95% CI 1.39-6.92), valve vegetations (HR 3.22, 95% CI 1.14-9.07), CAPS (HR 3.80, 95% CI 1.84-7.87), and requirement of MV (HR 2.22, 95% CI 1.03-4.80). Forty-two percent of patients required MV on the incident DAH episode. Patients presenting with severe thrombocytopenia (OR 6.42, 95% CI 1.77-23.30) or CAPS (OR 4.30, 95% CI 1.65-11.16) were more likely to require MV.
CONCLUSION
APS-associated DAH is associated with high morbidity and mortality, particularly when presenting with triple positivity, thrombocytopenia, valvular involvement, and CAPS.
Topics: Humans; Female; Adult; Male; Antiphospholipid Syndrome; Hemorrhage; Lung Diseases; Lupus Erythematosus, Systemic; Leukopenia; Risk Factors; Recurrence; Thrombocytopenia; Retrospective Studies; Multicenter Studies as Topic
PubMed: 37722463
DOI: 10.1016/j.clim.2023.109775 -
American Journal of Obstetrics and... Nov 2023We performed a systematic review to evaluate the clinical presentation and maternal and fetal outcomes in pregnancies with early-onset HELLP (hemolysis, elevated liver... (Review)
Review
OBJECTIVE
We performed a systematic review to evaluate the clinical presentation and maternal and fetal outcomes in pregnancies with early-onset HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome.
DATA SOURCES
PubMed, Ovid MEDLINE, Scopus, CINAHL, Cochrane Library, and ClinicalTrials.gov were queried from inception through January 1, 2023 with the following terms: "HELLP syndrome," "HELLP," "hemolysis, elevated liver enzymes, low platelets," "hemolysis, elevated liver enzymes, low platelets syndrome," "pre-viable," "peri-viable," "previable," "periviable," "first trimester," "second trimester," "before 23 weeks," "<23 weeks," "<23 week gestation," and "before 23 weeks gestation." We also included an additional case from our institution.
STUDY ELIGIBILITY CRITERIA
Abstracts, unpublished studies, and review articles were excluded, yielding 46 studies that met our inclusion criteria.
METHODS
Two reviewers (N.S.I. and M.H.M.) performed the study selection and subsequent data extraction independently, after which the results were reviewed together. PRISMA guidelines were followed, and our study was registered at PROSPERO (CRD42021292692).
RESULTS
A total of 55 patients had 58 pregnancies complicated by early-onset HELLP syndrome, including 3 with recurrent HELLP. The most common presenting signs/symptoms were abdominal pain (35/45; 78%), hypertension (32/49; 65%), nausea/vomiting (16/45; 36%), headache (13/45; 29%), and edema (8/45; 18%). Lactate dehydrogenase ≥600 IU/L was observed in 21 of 31 (68%) cases, whereas liver enzyme abnormalities and thrombocytopenia were reported in 48 of 51 (94%) and 50 of 54 (93%) cases, respectively. Maternal complications were encountered in 25 of 56 (45%) cases. The most common complications were hepatic (13/56; 23%), central nervous system-related (11/56; 20%), and respiratory (11/56; 20%). In 36 of 57 (63%) cases, pregnancy was terminated. Of the 21 continued pregnancies, early fetal death (at <20 weeks' gestation) was reported in 10 (48%), stillbirth in 6 (28%), and neonatal demise in 2 (10%). Living neonates were reported in 3 of 21 (14%) cases, all delivered at 23 weeks. The perinatal mortality rate was 73% (8/11). One case (2%) reported maternal death. Antiphospholipid syndrome was diagnosed in 14 of 29 (48%) cases.
CONCLUSION
Early-onset HELLP syndrome presents with symptoms similar to those observed in later gestation. Maternal complications are life-threatening, with the most common complications being hepatic, central nervous system-related, and respiratory. Fetal outcomes are poor.
Topics: Infant, Newborn; Female; Pregnancy; Humans; HELLP Syndrome; Hemolysis; Pregnancy Trimester, Second; Thrombocytopenia; Gestational Age
PubMed: 37150281
DOI: 10.1016/j.ajog.2023.04.046 -
Clinical Nutrition ESPEN Feb 2024Coenzyme Q10 (CoQ10) is a potent antioxidant and anti-inflammatory substance used to treat some rheumatic diseases. Our objective was to review the use of CoQ10 in... (Review)
Review
Coenzyme Q10 (CoQ10) is a potent antioxidant and anti-inflammatory substance used to treat some rheumatic diseases. Our objective was to review the use of CoQ10 in rheumatic diseases. PubMed/Medline, Embase, Scopus, and Web of Science databases were searched for articles on CoQ10 and rheumatic diseases between 1966 and April 2023. Twenty articles were found, including 483 patients. The investigated conditions were Fibromyalgia (FM) with 15 studies, Rheumatoid Arthritis (RA) with 3 studies, and Antiphospholipid Syndrome (APS) with 2 studies. After CoQ10 supplementation, RA patients observed improvements in disease activity index, inflammatory biomarkers (erythrocyte sedimentation rate), cytokine levels, and a decrease in malondialdehyde. In APS, CoQ10 improved endothelial function and decreased prothrombotic and proinflammatory mediators. Regarding FM, in most of the studies, the patients observed improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire (FIQ). The drug was well tolerated, with reports of minor side effects in two studies. CoQ10 supplementation seems to be efficacious as a complementary treatment for RA and FM. Upcoming studies with larger samples and including other rheumatic diseases are welcome.
Topics: Humans; Fibromyalgia; Ubiquinone; Antioxidants; Arthritis, Rheumatoid; Dietary Supplements
PubMed: 38220408
DOI: 10.1016/j.clnesp.2023.11.016 -
American Journal of Obstetrics &... Jun 2024Hepatic infarction is a rare complication of pregnancy most often associated with hemolysis, elevated liver enzymes, and low platelets syndrome. The objective of this... (Review)
Review
OBJECTIVE
Hepatic infarction is a rare complication of pregnancy most often associated with hemolysis, elevated liver enzymes, and low platelets syndrome. The objective of this review is to identify risk factors, present signs and symptoms, identify methods of diagnosis, and identify best management practices on the basis of published case reviews.
DATA SOURCES
PubMed and MEDLINE (Ovid) databases were searched for citations regarding hepatic infarction in pregnancy or the postpartum period from database inception until the study date of December 18, 2023. Key words included "liver infarction" or "hepatic infarction" and "pregnancy" or "obstetrics."
STUDY ELIGIBILITY CRITERIA
Case reviews or case series published in the English language were included. Our study was registered with the Prospective Register of Systematic Reviews (registration number CRD42023488176) and was conducted in accordance with the published Prospective Register of Systematic Reviews and Meta-analyses Of Observational Studies in Epidemiology guidelines.
METHODS
Included papers were evaluated for bias using a previously published tool.
RESULTS
A total of 38 citations documenting 50 pregnancies published between 1979 and 2023 were included. Of these, 34% had a history of hypertensive disease, 26% had antiphospholipid syndrome, and 22% had a history of thrombus. Of those without a preexisting diagnosis of antiphospholipid syndrome, 24% tested positive during hospitalization. Most patients presented with epigastric or right upper quadrant pain (78%), and 32% and 16% had severe blood pressure or mild blood pressure, respectively. Sixty-four percent of patients presented with transaminitis. Forty-six percent of patients delivered preterm, and 32% of pregnancies ended in intrauterine fetal demise, abortion, or early termination of pregnancy for maternal benefit. Computed tomography scans were used to confirm diagnosis of hepatic infarction in 58% of cases, magnetic resonance imaging in 14%, and ultrasound in 6%. In cases that described management, treatment was always multimodal, including antihypertensives (18%), therapeutic anticoagulation (45%), blood product transfusion (36%), plasma exchange or intravenous immunoglobulin (20%), and steroids (39%). Transfer to the intensive care unit was required in 20% of cases.
CONCLUSION
Hepatic infarction should be considered in all cases of hemolysis, elevated liver enzymes, and low platelets syndrome, but specifically in patients with a history of antiphospholipid syndrome who present with epigastric or right upper quadrant pain. The diagnosis can usually be confirmed with a computed tomography scan alone, and management should be prompt with supportive care, therapeutic anticoagulation, and steroids.
Topics: Humans; Pregnancy; Female; Infarction; Risk Factors; Antiphospholipid Syndrome; Pregnancy Complications; Liver; HELLP Syndrome
PubMed: 38621440
DOI: 10.1016/j.ajogmf.2024.101377 -
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 -
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 -
Indian Journal of Gastroenterology :... Oct 2023Both Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) have been linked to various prothrombotic (PT) conditions. The PT profile in Asians is different from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Both Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) have been linked to various prothrombotic (PT) conditions. The PT profile in Asians is different from the west and there are no nationwide epidemiological surveys from India. Hence, the present meta-analysis was aimed at analyzing the prevalence of acquired and hereditary thrombophilia among Indian patients with non-cirrhotic PVT and BCS.
METHODS
A comprehensive literature search of Embase, Medline and Scopus was conducted from January 2000 to February 2022 for studies evaluating the prevalence of various PT conditions in Indian patients with PVT and BCS. Pooled prevalence rates across studies were expressed with summative statistics.
RESULTS
Thirty-five studies with 1005 PVT patients and 1391 BCS patients were included in the meta-analysis. At least one PT condition was seen in 46.2% (28.7-63.7) of the PVT patients and 44.9% (37.3-60.7) of the BCS patients. Multiple PT conditions were seen in 13.0% (4.2-21.8) of the PVT patients and 7.9% (3.5-12.4) of the BCS patients. Among PVT patients, hyperhomocysteinemia was the commonest prothrombotic condition (21.6%) followed by protein C (PC) deficiency (10.7%), Janus kinase 2 (JAK-2) mutation (8.5%) and antiphospholipid antibodies (APLA) (7.5%). Among patients with BCS, PC deficiency was the commonest prothrombotic condition (10.6%) followed by methylenetetrahydrofolate reductase (MTHFR) mutation (9.8%), APLA (9.7%) and JAK-2 mutation (9.1%).
CONCLUSION
The PT profile in Indian patients with abdominal vein thrombosis is different from that of the western data with a lower prevalence of PT conditions in patients with BCS.
Topics: Humans; Budd-Chiari Syndrome; Portal Vein; Venous Thrombosis; Thrombosis; Mutation
PubMed: 37610562
DOI: 10.1007/s12664-023-01400-5 -
Clinical Immunology (Orlando, Fla.) Mar 2024Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of...
BACKGROUND
Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of patients presenting with APS-associated AH (APS-AH) through a retrospective cohort and a systematic literature review (SLR).
METHODS
We performed a mixed-source approach combining a multicenter cohort with an SLR of patients with incident APS-AH. We included patients from Mayo Clinic and published cases with persistent positivity for antiphospholipid antibodies and presenting with AH, demonstrated by imaging or biopsy. We extracted demographics, clinical characteristics, laboratory findings, treatment strategies, and outcomes (primary adrenal insufficiency and mortality). We used Kaplan-Meier and Cox models for survival analysis.
RESULTS
We included 256 patients in total, 61 (24%) from Mayo Clinic and 195 (76%) from the SLR. The mean age was 46.8 (SD 15.2) years, and 45% were female. 69% of patients had bilateral adrenal involvement and 64% presented adrenal insufficiency. The most common symptoms at presentation were abdominal pain in 79%, and nausea and vomiting 46%. Hyponatremia (77%) was the most common electrolyte abnormality. Factors associated with primary adrenal insufficiency were bilateral adrenal involvement at initial imaging (OR 3.73, CI; 95%, 1.47-9.46) and anticardiolipin IgG positivity (OR 3.80, CI; 95%, 1.30-11.09). The survival rate at five years was 82%. History of stroke was associated with 3.6-fold increase in mortality (HR 3.62, 95% CI; 1.33-9.85).
CONCLUSION
AH is a severe manifestation of APS with increased mortality. Most patients developed permanent primary adrenal insufficiency, particularly those positive for anticardiolipin IgG and bilateral adrenal involvement.
Topics: Female; Humans; Male; Middle Aged; Addison Disease; Antiphospholipid Syndrome; Hemorrhage; Immunoglobulin G; Multicenter Studies as Topic; Retrospective Studies; Adult
PubMed: 38244823
DOI: 10.1016/j.clim.2024.109906