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Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 91 records · Page 5Linked to original sources
PubMed2003

Prophylaxis of the antiphospholipid syndrome: a consensus report.

Hypothetical circumstances that may require prophylaxis for a potential antiphospholipid syndrome (primary prophylaxis), or in some instances when there already had been some manifestations ofthe syndrome (secondary prophylaxis), were presented to a panel of experts for their consideration on potential prophylactic intervention. These were subsequently presented to the participants in the First International Consensus on Treatment of the Antiphospholipid Syndrome. In most instances there was consensus in adding low dose aspirin, an exception being aspirin allergy when other antiaggregants could be used in nonpregnant subjects. General measures to prevent thrombosis and other vasoprotective actions should also be provided. Higher risk of fetal loss or thrombosis called for anticoagulation with coumadin in nonpregnant subjects or subcutaneous low molecular weight heparin in pregnant ones. When indicated, prophylaxis of the antiphospholipid syndrome should be provided in systemic lupus erythematosus patients who are being treated for their disease. In no instance should corticosteroids or immunosuppresants be given as prophylactic of an antiphospholipid syndrome.

Anticoagulants↗
PubMed2003

Venous thromboembolism in the antiphospholipid syndrome: management guidelines for secondary prophylaxis.

Venous thromboembolism (VTE) in patients suffering from the antiphospholipid syndrome (APS) has been reported in almost any location of the vessel tree and the risk of recurrences has been found in several studies to be more closely associated with the presence of lupus anticoagulant than with the positivity for anti-cardiolipin antibodies. The thrombophilic state of APS raises the problem of the secondary prophylaxis to avoid VTE recurrences. For APS patients with VTE, published data appear to support a longer warfarin treatment if compared with the standard management of antiphospholipid (aPL)-negative patients with VTE. The question of how long oral anticoagulant treatment should be continued for APS patients, however, remains unanswered. Concerning the intensity of anticoagulation, several authors recommend a target international normalized ratio (INR) between 3.0 and 4.0 to efficiently protect from VTE recurrences. A recent decision analysis study does support such a suggestion. On the contrary, in a few prospective studies regimens with lower target INRs appear to be effective, and some authors therefore recommend a target INR of between 2.0 and 3.0. Specific large and prospective trials are needed to address this question. Until such information becomes available, individualized treatment according to the patient's individual risk factors for both bleeding and thrombosis is the general practice.

Administration, Oral↗
PubMed2003

Stroke and the antiphospholipid syndrome: consensus meeting Taormina 2002.

Ischaemic stroke is the only neurological manifestation accepted as a clinical diagnostic criterion for the antiphospholipid syndrome (APS). This association is reasonably well established in patients first diagnosed with APS but is less clear in randomly selected stroke patients who test positive on one occasion for antiphospholipid antibodies and who have no other evidence of systemic autoimmune disease. We propose a grading system that posits stroke to be definitely, likely or possibly associated with antiphospholipid antibodies (aPL). Further, there are limited prospective data to determine appropriate treatment. There is controversy as to whether the presence of aPL even increases risk of a recurrent stroke or other thromboembolic event, although data point to persistent medium-high titre aCL and/or LA as risk factors for recurrence. In the absence of data to guide clinicians on the best treatment, we cannot make strong recommnendations as to optimal therapy, nor can we propose clear consensus treatment guidelines.

Administration, Oral↗
PubMed2003

Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report.

The Committee reviewed cardiac involvement in the antiphospholipid antibody syndrome. The Committee's recommendations are: Valve abnormalities: anticoagulation is recommended for symptomatic patients with valvulopathy. Prophylactic antiplatelet therapy may be appropriate for asymptomatic patients (recommended by 13/17 experts in an independent review). Committee members disagreed whether corticosteroid therapy is helpful, but agree that distinguishing among presumptive valvulitis (valve thickening on echocardiogram), valve deformity and vegetations is important, as treatment implications may differ. Occlusive arterial disease (angina, myocardial infarction): the Committee recommends aggressive treatment of all risk factors for atherosclerosis (hypertension, hypercholesterolaemia, smoking) and liberal use of folic acid, B vitamins and cholesterol-lowering drugs (preferably statins). Hydroxychloroquine for cardiac protection in APS patients may be considered. The Committee also recommends warfarin anticoagulation for those who have suffered thrombosis in the absence of atherosclerosis, but recognizes that developing data may support the use of antiplatelet agents instead. Intracardiac thrombi: the Committee recommends intensive warfarin anticoagulation, and consultation with cardiac surgeons when appropriate. Ventricular dysfunction: the Committee has no recommendations on this aspect of cardiac disease. Pulmonary hypertension: the Committee recommends intensive anticoagulation with warfarin and clinical trials of bosentan, epoprostenol and other new agents.

Anticoagulants↗
PubMed2003

Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies.

Although many types of neurological disorders and events have been described in association with antiphospholipid antibodies (aPL) and the antiphospholipid syndrome (APS), only ischaemic stroke is reasonably well established and accepted as a diagnostic criterion for the syndrome. We propose to evaluate, classify and rank the association of other neurological manifestations as possible, probable, or definite according to the data available from clinical studies and animal models. By these criteria, none of the neurological disorders or events such as epilepsy, psychiatric disease, dementia, transverse myelitis, multiple sclerosis-like disease, chorea, migraine, Guillian-Barrè syndrome, and sensory-neural hearing loss, can be definitely associated with aPL or APS.

Antibodies, Antiphospholipid↗
PubMed2003

Treatment of pregnant patients with antiphospholipid syndrome.

Antiphospholipid Syndrome (APS) has been widely recognized as a risk factor for the recurrence of both thrombosis and pregnancy losses; however the optimal treatment of patients is debatable. The aim of this paper was to establish a consensus among experts on the treatment of APS in pregnancy. A questionnaire that described possible different clinical situations was sent to the International Advisory Board of the 10th International Congress on Antiphospholipid Antibodies. Sixteen experts from different medical branches and different geographic areas sent their replies. The consensus was that treatment for APS pregnant patients should be low molecular weight heparin (LMWH) and low dose aspirin (LDA). The dosage, and frequency of LMWH depends on different situations, including the body weight and past history. Patients with previous thromboses usually receive two injections per day. Warfarin can also be used from 14 to 34 weeks, for patients with previous stroke or severe arterial thromboses. The use of intravenous immunoglobulin (IVIG) seems to be restricted to patients with pregnancy losses despite conventional treatment. The experts usually advised barrier methods of contraception, intrauterine device (if the patient is not taking corticosteroids) or progestins. Oral contraception with oestrogens was usually avoided.

Adult↗
PubMed2003

Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines.

The term 'catastrophic' antiphospholipid syndrome (APS) is used to define an accelerated form of APS resulting in multiorgan failure. Although catastrophic APS patients represent less than 1% of all patients with APS, they are usually in a life-threatening medical situation that requires high clinical awareness. The careful and open discussion of several proposals by all participants in the presymposium workshop on APS consensus, held in Taormina on occasion of the 10th International Congress on aPL and chaired by Munther A Khamashta and Yehuda Shoenfeld (29 September 2002), has allowed the acceptation of a preliminary set of classification criteria. On the other hand, the optimal management of catastrophic APS must have three clear aims: to treat any precipitating factors (prompt use of antibiotics if infection is suspected, amputation for any necrotic organ, high awareness in patients with APS who undergo an operation or an invasive procedure), to prevent and to treat the ongoing thrombotic events and to suppress the excessive cytokine 'storm'. Anticoagulation (usually intravenous heparin followed by oral anticoagulants), corticosteroids, plasma exchange, intravenous gammaglobulins and, if associated with lupus flare, cyclophosphamide, are the most commonly used treatments for catastrophic APS patients.

Antiphospholipid Syndrome↗
PubMed2003

Systemic antiphospholipid syndrome.

The antiphospholipid syndrome (APS) was reported in the early 1980s as a triad of manifestations. Since than it became one of the most systemic conditions. Almost any organ and tissue may be involved in the disease, including the brain, the heart, the placenta, the endocrine system, the blood, the kidneys and many more. In the article it is suggested to add to the syndrome the word systemic in analogy to its sister condition, systemic lupus erythematosus.

Antiphospholipid Syndrome↗
PubMed2003

TNFalpha DNA vaccination prevents clinical manifestations of experimental antiphospholipid syndrome.

Naked DNA encoding TNFalpha was introduced to BALB/c mice with experimental antiphospholipid syndrome (APS) induced by beta2GPI. Administration of naked DNA encoding TNFalpha resulted in the generation of immunological memory to its gene product, associated with elevated circulating anti-TNFalpha antibodies. Enriched IgG fraction of the mouse anti-TNFalpha was biologically active since it prevented endothelial cell activation by TNFalpha e.g., inhibition of monocyte adhesion to activated endothelial cells (HUVEC). Mice immunized with beta2GPI, vaccinated with TNFalpha DNA at an early stage of disease development, showed decreased titres of circulating anti-beta2GPI antibodies as compared to the group of mice vaccinated with a control naked DNA. The reduction of antiphospholipid antibody production was followed by amelioration of the foetal loss, increased platelet count to normal values as well as normalization of the prolonged aPTT. APS mice which were introduced to the TNFalpha DNA vector at a later stage of the disease development, showed less improvement in their clinical manifestations. The current study suggests a way in which a DNA vaccine can be employed for induction of a protective immunity in experimental APS.

Animals↗
PubMed2003

Oxidized low-density lipoprotein as a risk factor of thrombosis in antiphospholipid syndrome.

Beta2-Glycoprotein I (beta2-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome (APS). We recently reported that oxidized LDL(oxLDL) is subsequently targeted by beta2-GPI and anti-beta2-GPI auto-Abs and that-carboxyl variants of 7-ketocholesteryl esters, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and 7-ketocholesteryl-12-carboxy (keto) octadodecanoate (oxLig-2), are ligands for beta2-GPI (J Lipid Re 2001; 42: 697; J Lipid Res 2002; 43: 1486). These beta2-GPI ligands provide an electrostatic interaction between oxLDL and beta2-GPI followed by forming stable complexes (such as Schiff base adducts). The omega-carboxyl function in these ligand is responsible for beta2-GPI binding to oxLDL and the oxLDL-beta2-GPI complexes are anti-beta2-GPI auto-Ab-dependently taken up by macrophages (i.e., by phagocytosis). Our recent observations are consistent with the evidence that beta2-GPI co-localizes with lymphocytes and mononuclear cells in human athero-plaques. Thus, autoimmune thrombogenesis (atherogenesis) is linked to interaction of anti-beta2-GPI Abs with the beta2-GPI-oxLDL complexes. We propose an alternative idea, that an immune response against the beta2-GPI-oxLDL complexes may be involved in mechanisms in the development of atherosclerosis, which has been explained by the theory of 'the response to injury'.

Antigen-Antibody Complex↗
PubMed2003

The effects of antiphospholipid antibodies obtained from women with SLE/APS and associated pregnancy loss on rat embryos and placental explants in culture.

Recurrent fetal loss occurs in approximately 1% of women. Autoimmune causes have been suggested as a factor in some of these cases. High rates of intrauterine fetal growth retardation and increased incidence of prematurity is associated with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). We found in previous studies that sera from SLE/APS patients when used as a culture medium for rat embryos were found to reduce embryonic growth and development, induce a high rate of embryonic anomalies and death and damage the yolk sac morphologically and functionally. In order to investigate the direct effect of IgG purified from women with SLE/APS on the growth and viability of embryos, we cultured 11.5-day-old rat embryos in their yolk sacs in the presence of IgG purified from SLE/APS patients with recurrent pregnancy loss (RPL). The IgG affected directly the embryo and yolk sac, reducing their growth. The purified IgG positive for anticardiolipin/anti-DNA antibodies reduced yolk sac and embryonic growth more than sera negative for these antibodies but positive for antiphosphatydilserine and for antilaminin. Monoclonal antiphosphatydilserine reduced yolk sac growth but the embryos remained intact. Following the observed damage to the yolk sac we cultured human placental explants at 5.5-8 weeks of pregnancy in sera from SLE/APS patients for 96 hours and found that these sera reduced placental trophoblastic cell growth, reduced their proliferation rate and increased their rate of apoptosis. Successful treatment of the women resulted in a correction of the damage induced in the cultured rat embryos and in the cultured placental explants.

Abortion, Habitual↗
PubMed2003

Neuronal-binding antibodies from patients with antiphospholipid syndrome induce cognitive deficits following intrathecal passive transfer.

Antiphospholipid antibodies (aPL) have been suggested to play a role in causing cognitive and behavioral impairments. In the present study we investigated the pathogenic potential of aPL by intracerebro-ventricular (ICV) administration of immunoglobulins (IgG) from patients with antiphospholipid syndrome (APS). IgG, purified from the sera of four APS patients, was tested for binding to normal mouse brain by immunohistological staining. These IgG (7.5 microg) were injected ICV unilaterally to male C3H mice. Mice injected with IgG purified from pooled sera derived from healthy subjects served as controls. The mice were examined neurologically for motor function and coordination, and cognitively in a Morris water maze. The cognitive tests were performed with the experimenter blinded to the treatment. The performance of the mice in four separate experiments was compared by analysis of variance with repeated measures. IgG from one APS patient was found to bind best to neuronal structures in the hippocampus and cerebral cortex. Mice (n = 43) injected with this IgG performed worse in the water maze compared to the controls (n = 45) with significant effects of the aPL IgG on the overall performance of the mice (treatment, P < 0.03), on learning throughout the experiment (treatment x day, P < 0.02) and on short term memory (treatment x day xtrial, P < 0.002). IgG injected from two of the three other patients also bound specifically to mouse brain neurons and produced an impairment in performance of the water maze. These results support the hypothesis that aPL that gain access to the central nervous system may play a direct role in the pathogenesis of neurological manifestations of APS.

Adult↗
PubMed2003

CNS dysfunction in the antiphospholipid syndrome.

Though many neurological deficits have been described in the antiphospholipid syndrome (APS), only stroke is well established and accepted as a diagnostic criterion in this disease. We review clinical data obtained from a large series of cases regarding stroke, dementia, epilepsy, chorea, migraine, white matter disease and behavioral changes in APS or linked to laboratory criteria such as antiphospholipid antibodies (aPL). The contribution of animal models to our understanding of these manifestations of APS is stressed, especially regarding the cognitive and behavioral aspects for which we have established model systems in the mouse. These models utilize immunization of mice with beta2-glycoprotein I, a central autoantigen in APS, which induces persistent high levels of aPL. These mice develop hyperactive behavior after a period of four to five months as well as deficits in learning and memory and are potentially valuable as a system in which to study the pathogenesis and treatment of cognitive and behavioral aspects of APS. Another model we have developed, in which IgG from APS patients induce depolarization of brain synaptoneurosomes, may serve as a model for the pathogenesis of epilepsy in APS.

Animals↗
PubMed2003

Anti-cardiolipin and anti-beta2-glycoprotein I (beta2GP-I) antibody assays as screening for anti-phospholipid syndrome.

BACKGROUND: Antiphospholipid antibodies are a family of autoantibodies that exhibit a broad range of target specificities and affinities, all recognizing various combinations of phospholipids, phospholipid binding proteins or both. OBJECTIVE: To evaluate the frequency of anticardiolipin (aCL) or anti-beta-2 glycoprotein I (anti-beta2GPI) antibodies in a cohort of patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome and other rheumatic and infectious conditions. METHODS: Sera were drawn from 226 patients with PAPS (n= 66), SAPS (n= 60), rheumatoid arthritis (RA) (n= 30), scleroderma (SSc) (n= 30) or syphilis (n= 30). IgG, IgM, IgA aCL and anti-beta2GPI antibodies were determined for all patients. We employed Varelisa diagnostic kits (Pharmacia Diagnostics GmbH & Co.KG, Germany). RESULTS: In APS patients: aCL and anti-betaGP1 antibodies were detected in 81.8% and 70% in PAPS and SAPS patients, respectively. In PAPS, aCL were detected in 71.2%, and anti-beta2GP1 in 50% of patients. In SAPS, aCL were detected in 63.3%, and anti-beta2GP1 in 53.3% of patients. In syphilis, aCL and anti-beta2GP1 antibodies were detected in 46.7% of patients in low levels: aCL in 36.7% and anti-beta2GP1 in 20% of patients. aCL antibodies were detected in 10%, 13.3%, and 0% of RA patients, SSc patients, and healthy persons, respectively. Anti-beta2GP1 antibodies were not detected in RA patients, SSc patients, and healthy persons. CONCLUSIONS: aCL and anti-beta2GP1 antibodies are more frequently found in sera of APS patients, and can be found in low levels in syphilis. Anti-beta2GP1 assay found to be more specific than aCL in antiphospholipid antibodies determination.

Antiphospholipid Syndrome↗
PubMed2002

Successful pregnancy outcome in a patient with Gaucher's disease and antiphospholipid syndrome.

Gaucher's disease is characterized by increased incidence of several autoantibodies, but autoimmune phenomena are rare in Gaucher patients. We report the first occurrence of Gaucher's disease and antiphospholipid syndrome in the same patient. A 27-year-old woman with hepatosplenomegaly and thrombocytopenia who was diagnosed as having Gaucher's disease with the genotype 1226G/1226G developed Coombs'-positive hemolytic anemia, recurrent abortions, and a high titer of IgG and IgM anticardiolipin antibodies constituting the diagnosis of antiphospholipid syndrome. A successful pregnancy outcome was achieved by combined therapy with aspirin, low-molecular-weight heparin, prednisone, and enzyme replacement therapy with imiglucerase. The possible pathogenicity of antiphospholipid antibodies found in the sera of many asymptomatic Gaucher patients should be further clarified.

Adult↗
PubMed2002

Immunization of naive BALB/c mice with human beta2-glycoprotein I breaks tolerance to the murine molecule.

OBJECTIVE: Immunization of naive mice with beta2-glycoprotein I (beta2GPI) leads to the generation of pathogenic anticardiolipin antibodies associated with clinical manifestations of the antiphospholipid syndrome (APS). The aim of this study was to determine whether immunization of naive mice with human beta2GPI, which shares homology with mouse beta2GPI molecules, breaks tolerance to murine beta2GPI and leads to the generation of anti-mouse beta2GPI. METHODS: Twenty-four female BALB/c mice were immunized in the footpads with 10 microg of human beta2GPI. Twelve age- and sex-matched BALB/c mice were immunized in the same manner with Freund's complete adjuvant and served as controls. The reactivity of whole sera, polyclonal IgG, and affinity-purified anti-beta2GPI IgG antibodies against human, bovine, and mouse beta2GPI was evaluated by enzyme-linked immunosorbent assay. RESULTS: High titers of anti-human beta2GPI IgG antibodies were detected 1 month after immunization. Progressively increasing titers against murine and bovine beta2GPI were recorded 1-4 months after injection. CONCLUSION: Immunization of mice with human beta2GPI resulted in the generation of antibodies reacting with human, bovine, and murine beta2GPI. The loss of tolerance to mouse beta2GPI is attributable to the high interspecies homology of beta2GPI. These results may point to molecular mimicry as a possible cause of APS.

Animals↗