Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1827-1832 ◽  
Author(s):  
Monica Galli ◽  
Davide Luciani ◽  
Guido Bertolini ◽  
Tiziano Barbui

To formally establish the risk of lupus anticoagulants and anticardiolipin antibodies for arterial and venous thrombosis, we ran a MEDLINE search of the literature from 1988 to 2000. Studies were selected for their case-control (11), prospective (9), cross-sectional (3), and ambispective (2) design. They provided or enabled us to calculate the odds ratio with 95% confidence interval (CI) of lupus anticoagulants and/or anticardiolipin antibodies for thrombosis in 4184 patients and 3151 controls. Studies were grouped according to the antibody investigated. Five studies compared lupus anticoagulants with anticardiolipin antibodies: the odds ratio with 95% CI of lupus anticoagulants for thrombosis was always significant. None of them found anticardiolipin antibodies were associated with thrombosis. Four studies analyzed only lupus anticoagulants: the odds ratio with 95% CI was always significant. The risk of lupus anticoagulants was independent of the site and type of thrombosis, the presence of systemic lupus erythematosus, and the coagulation tests employed to detect them. Sixteen studies served to assess 28 associations between anticardiolipin antibodies and thrombosis: the odds ratio with 95% CI was significant in 15 cases. Anticardiolipin titer correlated with the odds ratio of thrombosis. In conclusion, the detection of lupus anticoagulants and, possibly, of immunoglobulin G (IgG) anticardiolipin antibodies at medium or high titers helps to identify patients at risk for thrombosis. However, to take full advantage of the conclusions provided by the available evidence, there is an urgent need to harmonize investigational methods.

1988 ◽  
Vol 60 (02) ◽  
pp. 217-219 ◽  
Author(s):  
B Lesperance ◽  
M David ◽  
J Rauch ◽  
C Infante-Rivard ◽  
G E Rivard

SummaryLupus anticoagulants (LA) and anticardiolipin antibodies have been strongly associated with recurrent abortion and fetal death. Because steroids have been reported to improve the fetal outcome of LA associated pregnancies, presumably by decreasing the levels of LA, it becomes desirable to have a simple and reliable test to monitor the levels of the putative antibody. To this effect, we assessed the capacity of the following coagulation tests to detect the presence of LA in serial dilutions of patient plasma with pooled normal plasma: kaolin clotting time (KCT), tissue thromboplastin inhibition test (TTIT), dilute Russell Viper venom time (DRVVT) and activated partial thromboplastin time with standard and high concentrations of phospholipids (SC and HCAPTT). All samples were also evaluated for the presence of anticardiolipin antibodies with an ELISA. The KCT was able to detect LA at a much greater dilution in normal plasma than any of the other clotting assays. The ELISA was comparable to KCT in its ability to detect high dilutions of LA.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1509.1-1510
Author(s):  
T. Klein ◽  
S. Tiosano ◽  
A. Chohen ◽  
H. Amital

Background:Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem inflammatory lesions affecting many organ systems in the body. Familial Mediterranean fever (FMF) is an autosomal recessive disease of chronic autoimmune inflammation characterized by frequently relapsing self-limiting fever and inflammation that may be localized in peritoneum, pleura, joint or skin.1Previous studies have described the similarity of clinical symptoms of FMF among SLE patients. However, the literature on this topic is inconsistent and based mostly on case reports.2-4Objectives:To examine the proportions of coexistence of FMF among SLE patients compared to the general population. We hypothesized that the proportion of FMF among SLE patients is higher than the general population.Methods:This cross-sectional study used the Clalit Health Services database, the largest Health Maintenance Organization in Israel, serving 4,400,000 members. SLE patients were compared to age- and sex-matched controls. Chi- was used for univariate analysis.Results:The study included4886 SLEpatients and 24430 age- and sex-matched controls. The SLE group had a significantly higher proportion of FMF patients compared to non-SLE controls (0.68% and 0.21% respectively; p < 0.001).Table 1. All study populationTable 1.SLE patients and matched controls basic characteristicsNo SLESLEp.overallN=24430N=4886Age51.2±16.551.2±16.51.000Gender: Female20100 (82.3%)4020 (82.3%)1.000FMF52 (0.21%)33 (0.68%)<0.001Table 2. StratificationTable 2.comparison of FMF patients with and without SLEFMF without SLEFMF with SLEp.overallN=52N=33Age44.6±13.750.5±17.70.106Gender: Female45 (86.5%)26 (78.8%)0.523Conclusion:FMF was found to be more common amongst SLE patients compared to matched controls.The current study results suggest that the occurrence of SLE turn patients with an appropriate genetic and environmental setting to develop also FMF. This cross-sectional study sheds light on the coexistence of these two diseases, autoimmune and autoinflammatory.References:[1]Kucuk A, Gezer IA, Ucar R, Karahan AY. Familial mediterranean fever.Acta Medica (Hradec Kralove). 2014;57(3):97-104.[2]Lidar M, Zandman-Goddard G, Shinar Y, Zaks N, Livneh A, Langevitz P. SLE and FMF: A possible negative association between the two disease entities–report of four cases and review of the literature.Lupus. 2008;17(7):663-669.[3]Erten S, Taskaldiran I, Yakut ZI. Are systemic lupus erythematosus patients carrying MEFV gene less prone to renal involvement? report of three cases and review of the literature.Ren Fail. 2013;35(7):1013-1016.[4]Shinar Y, Kosach E, Langevitz P, et al. Familial mediterranean Fever gene (MEFV) mutations as a modifier of systemic lupus erythematosus.Lupus. 2012;21(9):993-998.Disclosure of Interests: :None declared


1998 ◽  
Vol 79 (02) ◽  
pp. 282-285 ◽  
Author(s):  
Josep Ordi-Ros ◽  
Francesc Monegal-Ferran ◽  
Nuria Martinez ◽  
Fina Cortes-Hernandez ◽  
Miquel Vilardell-Tarres ◽  
...  

SummaryObjective: To evaluate the usefulness of IgA antiphospholipid antibodies as markers of thrombosis and/or antiphospholipid antibody syndrome. Patients and Methods: A cross-sectional study design in a tertiary, university-based, autoimmune reference hospital. Seven-hundred ninety-five patients classified into five different groups – autoimmune diseases (255), deep vein thrombosis (153), transitory ischemic attacks (108), obstetric complications (196), infectious diseases (83) and controls (81) – were tested for IgA, IgG and IgM aPL, and lupus anticoagulant. Plasma and serum samples were drawn for detection of aPL using an internationally standardized ELISA method and LA was carried out using coagulometric assays. Results: True IgA aPL were found only in two patients with systemic lupus erythematosus; these patients were also positive to IgG aPL. Conclusion: The incidence of true positivity to IgA anticardiolipin antibodies is extremely low. Their determination was not helpful in diagnosing the antiphospholipid syndrome or in explaining thrombotic events or aPL related manifestations – fetal loss – in the groups studied.


2008 ◽  
Vol 14 (3) ◽  
pp. 332-337 ◽  
Author(s):  
Gary W. Moore ◽  
Savita Rangarajan ◽  
Geoffrey F. Savidge

Lupus anticoagulants are a heterogeneous group of autoantibodies detected by their effects on phospholipid-dependent coagulation assays. Persistent lupus anticoagulants are associated with thrombotic disease, but not all are clinically significant. Antibody heterogeneity and reagent and test variability dictate that at least 2 tests, of different types, should be used to screen lupus anticoagulants. The objective of this study was to investigate whether the activated seven lupus anticoagulant assay detects clinically significant antibodies. Eighty-two patients with antiphospholipid syndrome (APS) and 32 with systemic lupus erythematosus + positive for activated seven lupus anticoagulant and who were without thrombosis, who were positive by activated seven lupus anticoagulant assay, were investigated for lupus anticoagulants by dilute Russell's viper venom time, dilute activated partial thromboplastin time, and Taipan snake venom time, and for anticardiolipin antibodies. Fifty-seven of the APS patients were positive for lupus anticoagulants in multiple assays, 25 in activated seven lupus anticoagulant alone. Fourteen of the latter group were previously positive in other antiphospholipid antibodies assays, and 11 had only been positive for lupus anticoagulants by activated seven lupus anticoagulant. Twenty-eight had elevated anticardiolipin antibodies, 6 of whom were from the group that was positive in activated seven lupus anticoagulant only. Eight of the systemic lupus erythematosus + lupus anticoagulants (without thrombosis) patients were positive for lupus anticoagulant by activated seven lupus anticoagulant alone and had only been positive in activated seven lupus anticoagulant previously, and none had elevated anticardiolipin antibodies. The remaining 24 patients were lupus-anticoagulant positive in multiple assays, and 9 had elevated anticardiolipin antibodies. Dilute Russell's viper venom time and Dilute activated partial thromboplastin time are widely used to detect lupus anticoagulants and are considered to detect clinically significant antibodies. Activated seven lupus anticoagulant detected antibodies in APS patients who were positive by these assays and also lupus anticoagulants undetectable by the dilute Russell's viper venom time/dilute activated partial thromboplastin time reagents used, demonstrating its utility as a first-line or second-line assay.


2010 ◽  
Vol 128 (5) ◽  
pp. 263-267 ◽  
Author(s):  
Mahendra Narain Mishra ◽  
Varinder Singh Bedi

CONTEXT AND OBJECTIVE: Venous thrombosis occurs as a result of interaction of genetic and acquired factors including activated protein C resistance (APC-R), fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and anticardiolipin antibodies. This study was aimed at determining the prevalence of these common thrombophilia markers in Asian Indians with primary venous thrombosis. DESIGN AND SETTING: This was a cross-sectional study carried out in Mumbai. METHODS: Samples from 78 patients with a confirmed diagnosis of venous thrombosis and 50 controls were tested. Semi-quantitative estimation (functional assays) of protein C, protein S and antithrombin was performed. Quantitative estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants were screened using lupus-sensitive activated partial thromboplastin time and β2-glycoprotein-I dependent anticardiolipin antibodies were estimated by ELISA. APC-R was measured using a clotting-based method with factor V deficient plasma and Crotalus viridis venom. Statistical analysis was performed using Epi-info (version 6). RESULTS: The popliteal vein was the most commonly involved site. Forty-four samples (56%) gave abnormal results. The commonest were elevated fibrinogen and APC-R (17.9% each), followed by low protein S (16.6%). CONCLUSIONS: This study confirms the literature findings that fibrinogen level estimation and screening for APC-R are important for the work-up on venous thrombosis patients since these, singly or in combination, may lead to a primary thrombotic episode. The frequency of the other thrombophilia markers was higher among the patients than among the controls, but without statistically significant difference.


2014 ◽  
Vol 41 (4) ◽  
pp. 401-406 ◽  
Author(s):  
Daniel Ortiz ◽  
Eric M. Siegal ◽  
Christopher Kramer ◽  
Bijoy K. Khandheria ◽  
Ernesto Brauer

Nontyphoidal Salmonella, especially Salmonella enterica, is a rare cause of endocarditis and pericarditis that carries a high mortality rate. Proposed predisposing conditions include immunodeficiency states, congenital heart defects, and cardiac valve diseases. We present 2 cases of cardiovascular salmonellosis. The first case is that of a 73-year-old woman with mechanical mitral and bioprosthetic aortic valves who died from sequelae of nontyphoidal Salmonella mitral valve vegetation, aortic valve abscess, and sepsis. The second case is that of a 62-year-old man with a recent systemic lupus erythematosus exacerbation treated with oral steroids, who presented with obstructive features of tamponade and sepsis secondary to a large S. enteritidis purulent pericardial cyst. He recovered after emergent pericardial drainage and antibiotic therapy. Identifying patients at risk of cardiovascular salmonellosis is important for early diagnosis and treatment to minimize sequelae and death. We reviewed the literature to identify the predisposing risk factors of nontyphoidal Salmonella cardiac infection.


Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 2958-2963
Author(s):  
JS Ginsberg ◽  
C Demers ◽  
P Brill-Edwards ◽  
M Johnston ◽  
R Bona ◽  
...  

The objective of this study is to determine whether patients with systemic lupus erythematosus (SLE) and anticardiolipin antibodies (ACA) have biochemical evidence of an ongoing prothrombotic state. Using a cross-sectional analysis of a cohort design in an outpatient SLE clinic setting, 43 consecutive patients with SLE participated. Patients underwent clinical and laboratory evaluations on two separate occasions at least 3 months apart. As part of the clinical evaluation, the following were ascertained: (1) the ongoing use of warfarin therapy; (2) the presence of prior venous and arterial thromboembolic disease by history, critical review of objective tests, and examination for reflux in the deep veins of the legs as an indicator of venous thrombosis; and (3) disease-related activity by performing a lupus activity criteria count (LACC). As part of the laboratory evaluation, blood was taken on both occasions and assayed for prothrombin fragments (F1 + 2) and fibrinopeptide A (FPA), as indices of thrombin generation and activity, respectively, and ACA. For the analyses, patients were classified as ACA+ if the assay was abnormal on both occasions and ACA- if the assay was negative on both occasions or negative on one occasion and positive on the other. ACA+ patients had: (1) a significantly higher mean level of F1 + 2 (1.07 nmol/L) than ACA- patients (0.79 nmol/L; P = .02) and patients receiving warfarin (0.47 nmol/L; P = .009) and (2) a significantly higher mean level of FPA (1.01 nmol/L) than ACA- patients (0.45 nmol/L; P = .02). When patients with prior thromboembolism were excluded from the analysis, significant differences in the mean levels of F1 + 2 and FPA between ACA+ and ACA- patients were still seen, whereas when patients with prior thromboembolism and/or active disease were excluded from the analysis, a significant difference in the mean level of FPA and a nonsignificant trend in the mean level of F1 + 2 were seen. The results of this study support the hypothesis that the presence of ACA in SLE patients is associated with an ongoing prothrombotic state.


1999 ◽  
Vol 81 (05) ◽  
pp. 695-700 ◽  
Author(s):  
Guido Finazzi ◽  
Francesca Norbis ◽  
Stefana Marziali ◽  
Roberto Marchioli ◽  
Tiziano Barbui ◽  
...  

SummaryLupus anticoagulants belong to the family of antiphospholipid antibodies. They include two phospholipid-dependent inhibitors of coagulation that may be distinguished on the basis of specific coagulation profiles generated from the comparison of the ratios of the Kaolin Clotting Time (KCT) and the dilute Russell’s Viper Venom Time (dRVVT): when the ratio of the KCT exceeds that of the dRVVT, the plasma is allocated to the “KCT” coagulation profile, when the opposite occurs, the plasma is defined to belong to the “dRVVT” coagulation profile group. We prospectively followed-up a historical cohort of 100 consecutive patients with lupus anticoagulants referred to our Institution between January 1988 and October 1997 to investigate the relationship between their coagulation profile at diagnosis and the development of thrombosis during a median follow-up time of 37.5 months (range 1-115 months). Fifty-six patients were allocated to the “dRVVT” coagulation profile, whereas the other 44 displayed the “KCT” profile. Lupus anticoagulants were transient in 17 patients, without differences between the two groups. None of these patients developed clinical events before disappearance of the phospholipid-dependent inhibitors of coagulation. The 83 cases with persistent lupus anticoagulants consistently displayed the same coagulation profile they had been allocated to at entry. Fourteen patients developed 18 thromboembolic events during the follow-up, with an overall rate of thrombosis of 4.2% patients-year. Twelve of them belonged to the “dRVVT” coagulation profile, whereas the other 2 to the “KCT” profile (p = 0.03). The “dRVVT” coagulation profile gave an odds ratio of thrombosis of 5.25 (95% confidence interval [C.I.]: 1.17-23.50). Ten of the 14 patients who developed thrombosis during follow-up had already experienced thrombosis: a previous thrombotic event caused an odds ratio of recurrency of 2.72 (95% C.I.: 0.85-8.73) (p = 0.09). By multivariate analysis, the “dRVVT” coagulation profile was still associated with a trend to a higher risk of thrombosis, but the difference did not reach statistical significance. Increased levels of anticardiolipin antibodies (> 40 GPL and/or MPL units) were found in all the 14 patients (p = 0.0064). The “KCT” coagulation profile was significantly associated (p = 0.005) with moderate thrombocytopenia (platelets 50-150 × 109/l). Neither profile was found to represent a risk factor for the development of recurrent miscarriages, neoplastic diseases and death. In conclusion, the “dRVVT” profile appears to have predictive value with respect to the thrombotic complications suffered by patients with antiphospholipid antibodies.


2018 ◽  
Vol 46 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Konstantinos Tselios ◽  
Dafna D. Gladman ◽  
Paula Harvey ◽  
Shadi Akhtari ◽  
Jiandong Su ◽  
...  

Objective.Cardiac involvement in systemic lupus erythematosus (SLE) is often undiagnosed in its early phases. Specific heart biomarkers may identify patients at risk. We sought to investigate the prevalence and associated factors for such biomarkers in SLE.Methods.Brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) were measured simultaneously in 151 consecutive patients with no history of heart disease or pulmonary arterial hypertension (PAH). None had electrocardiographic abnormalities suggestive of acute coronary syndrome. Cross-sectional comparisons and logistic regression analyses were performed. Patients with abnormal biomarkers were investigated to delineate the specific cause.Results.Sixteen patients (16/151, 10.6%) had elevated BNP, and 9 of them also had abnormal cTnI. Compared to subjects with normal biomarkers, they were older, had longer disease and antimalarial (AM) use duration, and more frequently persistent creatine phosphokinase (CPK) elevation. Multivariable regression analysis showed prolonged AM treatment (> 5.6 yrs) and persistent CPK elevation to be important predictors for elevated cardiac biomarkers. Six patients were diagnosed with definite (based on endomyocardial biopsy, n = 2) or possible (based on cardiac magnetic resonance after exclusion of other causes) AM-induced cardiomyopathy (AMIC); all had both BNP and cTnI elevated. Alternative causes were identified in 5, while no definitive diagnosis could be made in the remaining patients.Conclusion.About 10% of patients with SLE had elevated myocardial biomarkers, in the absence of prior cardiac disease or PAH. One-third of them were diagnosed with AMIC. Prolonged AM therapy and persistent CPK elevation conferred an increased risk for abnormal BNP and cTnI, which might predict AMIC.


1997 ◽  
Vol 78 (03) ◽  
pp. 1008-1014 ◽  
Author(s):  
Ricardo R Forastiero ◽  
Marta E Martinuzzo ◽  
Graciela S Cerrato ◽  
Lucía C Kordich ◽  
Luis O Carreras

SummaryThe lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are clinically relevant because of their association with thrombosis and pregnancy loss. The group of antiphospholipid antibodies (aPL) includes antibodies primarily directed against various phospholipid-binding proteins, mainly β2-glycoprotein I (β2GPI) and prothrombin. Some studies suggest that there is an association between the presence of anti β2GPI antibodies (a(β2GPI) of IgG isotype and thrombosis. Therefore, aPL defined according to the plasma protein to which they are directed appear to be more appropriate for the evaluation of their clinical importance. Using home-made ELISAs we evaluated the presence of a(β2GPI and antiprothrombin antibodies (anti-II) of both isotypes (IgG and IgM) in a group of 233 patients with LA and/or aCL. Forty-four women had a history of pregnancy loss, 45 patients had a history of venous thrombosis (VT) and 32 of arterial thrombosis (AT). Patients from the autoimmune group (systemic lupus erythematosus and antiphospholipid syndrome) had a higher prevalence of aβ2GPI and/or anti-II than those from the miscellaneous group. In the univariate analysis, a significant association was shown between the presence of aβ2GPI-IgG (OR 3.2; 95% Cl 1.5-6.6) and previous VT, but not AT. Anti-II were related to VT but the multivariate analysis showed that aβ2GPI-IgG are the only independent risk factor for VT (OR 3.0; 95% Cl 1.3-6.2). The presence of aβ2GPI-IgM correlates well with a history of pregnancy loss (OR 2.6; 95% Cl 1.1-6.1). The coagulation tests profile showed that the clotting assays were more prolonged in patients having aCL, a(β2GPI or anti-II. But a higher prevalence of abnormal results was only found for the dilute Russell viper venom time in patients with VT, as compared to those without thrombosis (94.4% vs. 58.7%, p <0.02). The measurement of aβ2GPI of both isotypes could help to identify aPL-positive patients with a higher risk for thrombosis and pregnancy loss, although this association should be confirmed by prospective studies.


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