scholarly journals Recurrent Fetal Loss and Antiphospholipid Antibodies: Clinical and Therapeutic Aspects

1997 ◽  
Vol 5 (2) ◽  
pp. 183-191 ◽  
Author(s):  
O. Blétry ◽  
A.-M. Piette
Keyword(s):  
High Risk ◽  
Antiphospholipid Antibodies ◽  
Protein C ◽  
Fetal Loss ◽  
Annexin V ◽  
Murine Models ◽  
Recurrent Fetal Loss ◽  
The Third ◽  
Risk Patients ◽  
Syncytia Formation

Recurrent fetal losses indicate screening for antiphospholipid antibodies, especially after the third consecutive fetal loss, or when they occur after 12 weeks gestation or when the mother presents with thrombosis or other ailments of antiphospholipid syndrome. Fetal loss may be caused by thromboses of placental vasculature. There is no agreement concerning the mechanism of thromboses: protein C pathway and/or annexin V are the best candidates. When fetal loss occurs early during gestation, murine models suggest that antiphospholipid antibodies can also act on trophoblasts by inhibiting syncytia formation. Among the high risk patients with more than two fetal losses, an association of aspirin and heparin given early during gestation is successful in 70–80% of cases.

scholarly journals O-133. Skin biopsy in women with recurrent fetal loss: a method of diagnosing the presence of antiphospholipid antibodies?

1999 ◽  
Vol 14 (Suppl_3) ◽  
pp. 73-74
Author(s):  
G. Properzi ◽  
S. Francavilla ◽  
Cesare S. Di ◽  
N. Concordia ◽  
S. Colangeli ◽  
...  
Keyword(s):  
Skin Biopsy ◽  
Antiphospholipid Antibodies ◽  
Fetal Loss ◽  
Recurrent Fetal Loss

Anticardiolipin Antibodies Block the Inhibition by β2-Glycoprotein I of the Factor Xa Generating Activity of Platelets

1993 ◽  
Vol 70 (02) ◽  
pp. 342-345 ◽  
Author(s):  
Wei Shi ◽  
Beng H Chong ◽  
Philip J Hogg ◽  
Colin N Chesterman
Keyword(s):  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Fetal Loss ◽  
Factor Xa ◽  
Anticardiolipin Antibodies ◽  
Recurrent Fetal Loss ◽  
Glycoprotein I ◽  
Activated Platelets ◽  
Inhibit Factor

SummaryAntiphospholipid antibodies, defined either by lupus anticoagulant (LA) activity or positive anticardiolipin immunoabsorbent assay (ACA) are associated with a predisposition to thromboses, recurrent fetal loss or thrombocytopenia. The mechanisms for these predispositions remain undefined. We have enriched immunoglobulin fractions from two patient plasmas to obtain antibodies with LA activity but no ACA, or conversely, with ACA positivity but no LA, in order to investigate in vitro characteristics which might explain a thrombotic propensity. β2-glycoprotein I (β2-GPI), the plasma cofactor required for ACA binding to negatively charged phospholipid, has previously been shown to inhibit prothrombinase generation in the presence of activated platelets (8). We now report that β2-GPI, at physiological concentrations, inhibits the generation of factor Xa in the presence of activated gel-filtered platelets. Further, ACA interferes with this inhibition, resulting in protracted, unopposed factor Xa generation. This interference with β2-GPI, a natural anticoagulant component of plasma, is potentially prothrombotic. LA immunoglobulins behave differently and inhibit factor Xa generation in a manner similar to β2-GPI. These findings provide the basis for a previously unsuspected mechanism for thrombosis in patients with aPL.

Identification of Patients At High Risk for Recurrent Venous Thromboembolism by Whole Blood Gene Expression Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2305-2305
Author(s):  
Thomas L. Ortel ◽  
Michele Beckman ◽  
W Craig Hooper ◽  
Deborah A Lewis ◽  
Jen-Tsan A. Chi ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Whole Blood ◽  
Antiphospholipid Antibodies ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Low Risk ◽  
Risk Patients ◽  
Patient Groups ◽  
Recurrent Vte

Abstract Abstract 2305 Background. Recurrent venous thromboembolism (VTE) occurs in ∼30% of patients with spontaneous VTE after completion of a standard course of anticoagulant therapy. D-dimer levels and selected clinical parameters have been used to identify patients at low risk for recurrent VTE, who may safely discontinue antithrombotic therapy. We have used gene expression profiles to distinguish patients with a single VTE from patients with recurrent VTE. The purpose of this study was to extend this initial report and identify unique gene expression patterns from whole blood that correlate with different risk profiles for VTE recurrence. Methods. Patients with ≥1 prior VTE, with the first event occurring at age 18 years or older and >3 months from the most recent event were recruited for this study. Patients were allocated into 4 groups: (1) ‘low-risk’ patients had sustained ≥1 provoked VTE; (2) ‘moderate-risk’ patients had sustained 1 unprovoked VTE (with or without provoked VTE); (3) ‘high-risk’ patients had sustained ≥2 unprovoked VTE and had no evidence for antiphospholipid antibodies; and (4) antiphospholipid syndrome (APS) patients met established consensus criteria for APS. A similar number of individuals with no prior history of VTE were enrolled as a control population. Citrated plasma, serum and PAXgene RNA tubes were collected, processed and stored at −80°C until shipped to the CDC for analysis. Antiphospholipid testing was performed on all participants to confirm correct group distribution. Total RNA was isolated from whole blood drawn into PAXgene tubes. Following sample labeling and normalization, cRNA samples were hybridized to Illumina HT-12 Beadchips to assay whole genome gene expression with over 47,000 probes against human transcripts. Two hundred and twenty six unique samples passed initial quality control measures. Quality assessment of raw data was done using GenomeStudio. The raw data files were converted to a text file using the IlluminaExpression FileCreator in GenePattern and then log transformed, normalized and median-centered using Cluster. Both unsupervised (hierarchical clustering using Cluster) and supervised analyses (SAM) were used to identify genes that were differentially expressed between the groups. GATHER was used to help understand the biological processes and gene ontology of the gene lists generated by Cluster and SAM. Results. A total of 226 participants were enrolled into the study. Characteristics of the patient groups are summarized in the Table. Demographically, the groups were similar except that patients in the high-risk group tended to be older and were more likely male. The number of events per patient, and the proportion on anticoagulant therapy, increased with the risk group. Antiphospholipid antibodies were detected in several patients in each of the 3 non-APS VTE patient groups, but in most cases this was a single test positive; antiphospholipid antibodies were present in the majority of patients with APS, typically with more than one test positive (37 of 45 with complete testing, 82%). Preliminary analysis of the gene expression profiles using an unsupervised clustering by gene on the high-risk and low-risk groups identified multiple genes that distinguished the two groups, including 18 immune response genes identified by GATHER. These two patient groups were also distinguished by SAM analysis, and multiple genes in the MAPK signaling pathway that separated the two groups were identified by the KEGG pathways in GATHER. Additional analyses are being performed on all of the groups. Conclusions. Whole blood gene expression profiling can be used to develop profiles that distinguish patients with VTE who differ based on their risk of recurrent events. Individual genes identified in these profiles may provide biological insights into the molecular basis for recurrent VTE. Disclosures: Heit: Daiichi Sankyo: Honoraria; Ortho-McNeil Janssen: Honoraria; Covidien: Honoraria. Manco-Johnson:Octapharma AG: Consultancy; Bayer: Research Funding.

scholarly journals Association between the Prevalence of Antibodies to β2-Glycoprotein I, Prothrombin, Protein C, Protein S, and Annexin V in Patients with Systemic Lupus Erythematosus and Thrombotic and Thrombocytopenic Complications

2001 ◽  
Vol 47 (6) ◽  
pp. 1008-1015 ◽  
Author(s):  
Junzo Nojima ◽  
Hirohiko Kuratsune ◽  
Etsuji Suehisa ◽  
Yoshiaki Futsukaichi ◽  
Hachiro Yamanishi ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Lupus Erythematosus ◽  
Arterial Thrombosis ◽  
Plasma Proteins ◽  
Protein C ◽  
Significant Risk ◽  
Fetal Loss ◽  
Annexin V ◽  
Protein S ◽  
C Protein

Abstract Background: Anti-phospholipid (aPL) antibodies (Abs) frequently found in the plasma of patients with systemic lupus erythematosus (SLE) have been associated with thrombotic complications. Our aim was to clarify the roles in thrombosis of aPL Abs that react with complexes of phospholipids and plasma proteins such as β2-glycoprotein I (β2-GPI), prothrombin, protein C, protein S, and annexin V. Methods: We determined the prevalence of aPL Abs to various phospholipid-binding plasma proteins in SLE patients with arterial thrombosis (30 cases), venous thrombosis (19 cases), thrombocytopenia (14 cases), fetal loss (14 cases), and patients without complications (91 cases). The aPL Abs were measured by an ELISA system in which human plasma proteins (β2-GPI, prothrombin, protein C, protein S, and annexin V) were immobilized on γ-irradiated or plain polystyrene plates. Results: All types of aPL Abs were frequently observed in the patients with SLE when γ-irradiated polystyrene plates were used (51 of 168 cases positive for anti-β2-GPI, 94 of 168 cases positive for anti-prothrombin, 36 of 168 cases positive for anti-protein C, 47 of 168 cases positive for anti-protein S, and 50 of 168 cases positive for anti-annexin V), whereas no Abs to these plasma proteins were detected when plain polystyrene plates were used. Multivariate analysis confirmed that both anti-β2-GPI and anti-prothrombin Abs were significant risk factors for arterial thrombosis [odds ratios (ORs), 8.8 and 14.5, respectively; 95% confidence intervals (CIs), 3.2–25 and 1.8–116, respectively] but not for venous thrombosis. The presence of anti-protein S Abs was a significant risk factor for venous thrombosis (OR, 30.4; CI, 3.3–281) but not for arterial thrombosis. The only significant risk factor for fetal loss was the presence of anti-annexin V Abs (OR, 5.9; CI, 1.4–14.8). Conclusions: Patients with SLE frequently have some aPL Abs to β2-GPI, prothrombin, protein C, protein S, and annexin V. Thrombotic complications in SLE may depend on the antigenic specificities of these Abs, alone or in combination.

Lupus Anticoagulants/Antiphospholipid-Protein Antibodies: The Great Imposters

Lupus ◽  
1996 ◽  
Vol 5 (5) ◽  
pp. 431-435 ◽  
Author(s):  
DA Triplett
Keyword(s):  
Solid Phase ◽  
Fetal Loss ◽  
Annexin V ◽  
Protein S ◽  
Anticardiolipin Antibodies ◽  
Thromboembolic Events ◽  
Lupus Anticoagulants ◽  
Recurrent Fetal Loss ◽  
Clinical Complications ◽  
Venous Thromboembolic Events

Antiphospholipid-protein antibodies (APA) represent a family of immunoglobulins which recognize protein-phospholipid complexes. A variety of proteins have been implicated including: prothrombin, annexin V, β2-Glycoprotein I, and protein S. APA are detected utilizing either coagulation-based tests to identify lupus anticoagulants (LA) or solid phase ELISA assays to identify anticardiolipin antibodies (ACA). APA may be seen in a variety of different clinical settings including convalescence from infections, resulting from exposure to certain drugs, or in association with autoimmune diseases. Autoimmune APA have been linked to a variety of thromboembolic complications involving both arterial and venous sites. In addition, recurrent fetal loss has been linked to a APA. The underlying pathophysiology of the thromboembolic events remains controversial. Given the diversity of anatomic sites, more than one thromboembolic mechanism(s) is likely. Abnormalities of the protein C system most likely account for the venous thromboembolic events. Because of the spectrum of clinical complications, virtually any clinician may encounter patients with the APA syndrome (thrombosis, thrombocytopenia, recurrent fetal loss coupled with positive LA or ACA testing).

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