Recurrent thrombosis in antiphospholipid syndrome may be associated with cardiovascular risk factors and inflammatory response.
TL;DR: The results suggest that arterial hypertension and monocyte counts may be independent factors for thrombosis recurrence in APS, and may support the evaluation of therapeutic measures to a rigid control of blood pressures and modulation of inflammatory response in APs, as additional prophylaxis against the recurrence of vascular events.
About: This article is published in Thrombosis Research.The article was published on 2015-12-01. It has received 25 citations till now. The article focuses on the topics: Antiphospholipid syndrome & Thrombosis.
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TL;DR: Patients with APS associated with SLE or lupus-like syndrome had higher frequency of arthritis,leukopenia,antinuclear antibodies(ANA) and low complement levels, and female patients had a higher frequency than male patients of deep venous thrombosis in the lower limbs and LA.
Abstract: Objective To analyze the clinical and immunological manifestations of antiphospholipid syndrome(APS)in a cohort of 100 patients.Methods The clinical and serologic features of APS(Sapporo preliminary criteria)in 100 patients were analyzed retrospectively.Results The cohort consisted of 79 female patients and 21 male patients witb a mean age of 36±13 years at diagnosis.Primary APS was presented in 37% of patients;APS was secondary to systemic lupus erythematosus(SLE)in 46%,lupus-like syndrome in 14%. Eighty percent of the patients had thrombosis,43(54%)patients had venous thrombosis,18(22%)had arterial thrombosis,15(19%)had both arterial and venous thrombosis.4(5%)had thrombosis of microcirculation. Forty-two(52%)patients presented thrombosis at a single site,26(32%)at two sites,12(15%)at three or more sites.Forty-five(56%)patients experienced one thrombotic episode,20(25%)patients had only one re- currence,and 15(19%)had more thrombosis.The most common manifestations of thrombosis were deep vein thrombosis(36%),pulmonary embolism(30%)and stroke(26%),with heart,kidney,gastrointestinal tract and other organs involvements.Thirty-four(51%)female patients had spontaneous fetal losses including intrauter- ine fetus death and recurrent spontaneous abortion.Seventy-one(71%)patients developed thromboeytopenia. The presence of antieardiolipin antibody(ACL)was detected in 84 patients(84%).Among 90 patients with APS,alone ACL was detected in 38 patients(42%),both ACL and lupus anticoagulant(LA)were detected in 36(40%),LA alone in 16(18%).Patients with APS associated with SLE or lupus-like syndrome had higher frequency of arthritis,leukopenia,antinuclear antibodies(ANA)and low complement levels.Female patients had a higher frequency of leukopenia,ANA and ACL.Male patients had a higher prevalence of deep venous thrombosis in the lower limbs and LA.Conclusion APS is an autoimmune disorder characterized by recurrent arterial and venous thrombosis,fetal loss,or thrombocytopenia with the presence of ACL and/or LA.In APS secondary to with SLE,the patient's sex can modify the disease expression and define specific subsets of APS.
55 citations
TL;DR: Known neurological manifestations of APS are summarized, revisiting pathogenesis and current treatment options are revisited, and the reason why only a subgroup of patients develop non-criteria nervous system disorders is explained.
Abstract: Antiphospholipid syndrome (APS) is an autoimmune antibody-mediated condition characterized by thrombotic events and/or pregnancy morbidity in association with persistent positivity to antiphospholipid antibodies (aPL). The nervous system is frequently affected, as intracranial vessels are the most frequent site of arterial pathology. Over the course of years, many other neurological conditions not included in the diagnostic criteria, have been associated with APS. The pathogenic mechanisms behind the syndrome are complex and not fully elucidated. aPL enhance thrombosis, interfering with different pathways. Nevertheless, ischemic injury is not always sufficient to explain clinical features of the syndrome and immune-mediated damage has been advocated. This may be particularly relevant in the context of neurological complications. The reason why only a subgroup of patients develop non-criteria nervous system disorders and what determines the clinical phenotype are questions that remain open. The double nature, thrombotic and immunologic, of APS is also reflected by therapeutic strategies. In this review we summarize known neurological manifestations of APS, revisiting pathogenesis and current treatment options.
54 citations
Cites background from "Recurrent thrombosis in antiphospho..."
...The high risk of thrombosis recurrence, which can be seen in 5–16% of subjects (109), warrants long-term anticoagulation....
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TL;DR: This study evaluated five randomized controlled trials that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place.
Abstract: Background
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events.
Objectives
To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome.
Search methods
We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field.
Selection criteria
We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS.
Data collection and analysis
Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data.
Main results
We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ-5D-5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains.
The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low-quality evidence). Investigators reported similar rates of clinically relevant non-major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate-quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ-5D-5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low-quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]).
Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low-quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high-intensity warfarin treatment compared to the standard-intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low-quality evidence).
In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60).
Authors' conclusions
There is not enough evidence for or against NOACs or for high-intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high-intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future.
41 citations
TL;DR: The results demonstrated that simple clinical parameters easy to be collected can be used to predict rates of recurrence and to develop new clinical decision support systems to predict the rates of RVTE.
Abstract: The rates of recurrent venous thromboembolism (RVTE) vary widely, and its causes still need to be elucidated. Statistical multivariate methods can be used to determine disease predictors and improve current methods for risk calculation. The objective of this study was to apply principal component analysis to a set of data containing clinical records of patients with previous venous thromboembolism and extract the main factors that predict recurrent thrombosis. Records of 39 factors including blood and lipid parameters, hereditary thrombophilia, antiphospholipid syndrome, clinical data regarding previous thrombosis and treatment, and Doppler ultrasound results were collected from 235 patients. The results showed that 13 principal components were associated with RVTE and that 18 of 39 factors are the important for the analysis. These factors include red blood cell, white blood cell, hematocrit, red cell distribution width, glucose, lipids, natural anticoagulant, creatinine, age, as well as first deep vein thrombosis data (distal/proximal, d-dimer, and time of anticoagulation). The results demonstrated that simple clinical parameters easy to be collected can be used to predict rates of recurrence and to develop new clinical decision support systems to predict the rates of RVTE.
21 citations
TL;DR: Both the aPL-S and GAPSS have shown a degree of accuracy in identifying high-risk APS patients, especially those at a high risk of thrombosis, but there are several areas requiring improvement, and clinicians should be aware of, before these instruments are applied in clinical practice.
Abstract: Antiphospholipid syndrome (APS) is a clinical disorder characterised by thrombosis and/or pregnancy morbidity in the persistence of antiphospholipid (aPL) antibodies that are pathogenic and have pro-coagulant activities. Thrombosis in APS tends to recur and require prophylaxis; however, the stereotypical treatment for APS patients is inadequate and stratification of the thrombotic risks is important as aPL are prevalently observed in various diseases or elderly population. It is previously known that the multiple positive aPL or high titre aPL correlate to thrombotic events. To progress the stratification of thrombotic risks in APS patients and to quantitatively analyse those risks, antiphospholipid score (aPL-S) and the Global Anti-phospholipid Syndrome Score (GAPSS) were defined. These scores were raised from the large patient cohort data and either aPL profile classified in detail (aPL-S) or simplified aPL profile with classical thrombotic risk factors (GAPSS) was put into a scoring system. Both the aPL-S and GAPSS have shown a degree of accuracy in identifying high-risk APS patients, especially those at a high risk of thrombosis. However, there are several areas requiring improvement, or at least that clinicians should be aware of, before these instruments are applied in clinical practice. One such issue is standardisation of the aPL tests, including general testing of phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT). Additionally, clinicians may need to be aware of the patient’s medical history, particularly with respect to the incidence of SLE, which influences the cutoff value for identifying high-risk patients.
19 citations
Cites background from "Recurrent thrombosis in antiphospho..."
...tients [38] and in non-APS aPL carriers [24]....
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References
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TL;DR: The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification and showed gains in sensitivity and specificity.
Abstract: The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.
14,272 citations
"Recurrent thrombosis in antiphospho..." refers methods in this paper
...The diagnosis of SLE was performed according to established criteria [19,20]....
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TL;DR: The chronic hyperglycemia of diabetes is associated with long-term damage, dys-function, and failure of differentorgans, especially the eyes, kidneys, nerves, heart, and blood vessels.
13,077 citations
University of New South Wales1, Hospital for Special Surgery2, Hokkaido University3, University of Utah4, University of Texas Health Science Center at San Antonio5, Utrecht University6, University of Milan7, Geneva College8, Sheba Medical Center9, University of Brescia10, National and Kapodistrian University of Athens11
TL;DR: This document appraise the existing evidence on clinical and laboratory features of APS addressed during the forum and proposes amendments to the Sapporo criteria, including definitions on features ofAPS that were not included in the updated criteria.
5,699 citations
University of British Columbia1, East Kent Hospitals University Nhs Foundation Trust2, Newcastle University3, Johns Hopkins University4, University of Groningen5, University of York6, University of Calgary7, University of the Ryukyus8, Tufts University9, University of California, San Francisco10, Peking University11, University of Oxford12
3,645 citations
Johns Hopkins University1, University of Alabama at Birmingham2, University of Birmingham3, Oklahoma Medical Research Foundation4, Laval University5, University of Manchester6, University College London7, University of California, Los Angeles8, Lund University9, Northwestern University10, Hanyang University11, Dalhousie University12, University of Toronto13, McGill University14, North Shore-LIJ Health System15, Allegheny General Hospital16, University of California, San Diego17, University of Pennsylvania18, Monklands Hospital19, University of the Basque Country20, St Thomas' Hospital21, University of Copenhagen22, New York University23, University of North Carolina at Chapel Hill24, Karolinska Institutet25, SUNY Downstate Medical Center26, University of Manitoba27, Wake Forest University28, University of Louisville29, Emory University30, Istanbul University31, Medical University of South Carolina32, University of Texas Health Science Center at San Antonio33, Cedars-Sinai Medical Center34, University of Maryland, Baltimore35
TL;DR: The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE.
Abstract: Objective The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE. Methods The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios. Results Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001). Conclusion The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or antidouble-stranded DNA antibodies. (Less)
3,609 citations
"Recurrent thrombosis in antiphospho..." refers methods in this paper
...The diagnosis of SLE was performed according to established criteria [19,20]....
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