ISSN:1424-8832    

DOI:10.1159/000217096

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Laboratories are currently challenged with the problem of ruling out APA in a patient plasmas. In order to optimize the identification of these antibodies, it is necessary to institute a well-planned approach. Both coagulation assays for the identification of LA and solid phase ELISA assays for the identification of ACA are indicated. In the case of LA, it is often necessary to screen the patient plasma with more than one test system. If two screening tests are negative, no further evaluation for the presence of LA is indicated. However, it is imperative to also perform ACA testing. The literature describing LA and ACA testing is growing exponentially. Several new integrated test systems which seek to simplify the approach to the diagnosis of LA have been introduced. These systems employ one test performed under two different conditions (low and high PL concentration). This approach may prove to be the most cost-efficient way of establishing the diagnosis of LA.

ISSN:1424-8832    

DOI:10.1159/000217097

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Antiphospholipid antibodies (APA) comprise a family of immunoglobulins characterized by their pattern of reactivity in a number of laboratory tests. Included in this family are lupus anticoagulant (LA) anticardiolipin antibodies (ACA) and antibodies causing biologic false positive serologic tests for syphilis (BFP-STS). LA and ACA occur in a variety of conditions, including other autoimmunes disorders, infectious diseases, neoplasic disorders, in association with certain drugs and in otherwise healthy individuals. Clinical interest in LA and ACA is increasing. Antiphospholipid antibody syndrome is characterized by a triad of clinical features wich include fetal loss, thromboembolic disease and thrombocytopenia. Other clinical manifestations related with APA are livedo reticularis, cutaneous necrosis, hemolytic anemia, heart valve disease, chorea, migraina and obstetric problems as fetal growth retardation, pre-eclampsia, post-partum serositis or neonatal thrombosis or catastrophic antiphospholipid syndrome. Therapy is mainly directed against the widespread and diverse manifestations associated with the obstruction of small and large vessels. Long-term treatment with oral anticoagulation therapy is advised, even if the venous or arterial occlusion ocurred many years previously. In patients with primary antiphospholipid syndrome there is no evidence that the prophylactic administration of steroids or immunosuppression will prevent thromboembolic events. Although the administration of more energetic immunosuppression with cyclophosphamide in pulse form is effective in reducing elevated antibody levels, there is usually a rapid rebound to pretreatment levels shortly after discontinuation of the therapy. A history of recurrent fetal loss requires mandatory treatment during pregnancy. Although the actual prospective risk of pregnancy loss in women with antiphospholipid syndrome and prior pregnancy loss is unknown, it may exceed 60%. Because of this many investigators have treated women with antiphospholipid syndrome with either antiplatelet agents, immunosuppressive agents, or anticoagulants in an attempt to improve pregnancy outcome. Unfortunately, there is no unequivocal proof that any of these therapies are fully efficacious. Despite varying treatment protocols, the live birth rate with treatment was 70%, similar to that reported in the recent randomized clinical trial. Thrombocytopenia and autoimmune hemolytic anemia in patients with APA are treated similary as patients without APA. Treatment of asymptomatic patients isn’t indicated, because only approximately 10-15% of patients with APA developed complication

ISSN:1424-8832    

DOI:10.1159/000217098

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The objective of this study was to determine the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) in a large series of patients admitted to a departament of Internal Medicine. At the end of entry phase, 1014 patients were tested (488 males-526 females, mean age: 66,7 years, range 18-97). Seventy-two (7.1 %) patients were found APA positive at least once: 44 males and 28 females, mean age 69 years, range 23 to 94. Twenty fulfilled the criteria of Primary Antiphospholipid Antibody Syndrome: 10 patients were referred for deep vein thrombosis, 3 had history of deep vein thrombosis, 1 had both arterial thrombosis and a history of venous thrombosis; 2 had thrombocytopenia; 3 had stroke, 1 had a history of s troke. One patient had SLE according to ARA classification. The most frequent associated disease was cancer: 14 patients, 9 had evolutive malignant disease, 5 were in clinical remission of neoplasia. Other clinical conditions included chronic and/or acute alcoholic intoxication (n=8), severe atherosclerosis (n=4), leg ulcer (n=4). Insufficient data are available about the evolution, but 7 patients died in the year following diagnosis. Eight patients had fluctuations in APA detection: 2 initially APA positive became negative, 5 initially negative became positive and 1 patient was alternatively positive, negative and positive without steroid treatment. Thus, as expected, APA occur in a variety of clinical disorders. The association with cancer or alcoholic intoxication deserves further investigations.

ISSN:1424-8832    

DOI:10.1159/000217099

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000217100

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Presence of β2 Glycoprotein I (β2GPI), in addition to phos-pholipids, is an absolute requirement for binding APA. This binding is frequently observed with β2GPI coated alone, however many APA react only with β2GPI complexed to phospholipids, but not with phospholipids alone. We demonstrate that a subgroup of rabbit polyclonal antibodies to human β2GPI binds to this protein only when it is coated on a solid surface, but not if it is in solution. In addition, β2GPI present in goat serum is strongly fixed by the coated phospholipids and the complexes formed bind as well APA as the rabbit antibodies to β2GPI. The diluent used for testing APA, has a strong incidence on APA’s reactivity as it can be a source of β2GPI. Antibody binding to β2GPI, Proth-rombin, Protein S, and Annexin V, coated in the presence or in the absence of phospholipids, was tested in 55 patients with the antiphospholipid syndrome. The strongest binding of antibodies was observed in 39 plasma to a mixture of phospholipids and purified human β2GPI, however 17 samples also presented a significant reactivity to β2GPI alone. Nine plasmas contained antibodies to Prothrombin, 4 to Protein S, 3 to Annexin V, and 1 to Protein C. We conclude that most of the APA are directed to a complex of β2GPI and phospholipids although in some patients antibodies to β2GPI alone or to other phosphoslipid binding protei

ISSN:1424-8832    

DOI:10.1159/000217101

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Three types of Experimental Animal Models have been used to investigate APA. 1) Passive transfer of APA to nocive mice. Branch et al injected pregnant Balb/c mice with purified IgG APA from patients with recurrent fetal loss. 2) Active immunization with APA. Backimer et al immunized Balb/c mice with a human monoclonal APA carrying the pathogenic idiotypes. 3) Immunization with β2 glycoprotein I (β2 GPI) (APA cofactor).Using affinity chromatography, we separated two distinct populations of antibodies. One was specific for β2GPI without binding to PL. Another population had a dual specificity for PL and β2

ISSN:1424-8832    

DOI:10.1159/000217102

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000217103

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000217095

出版商:S. Karger AG    

年代:1994

数据来源: Karger