Anti-β2-glycoprotein I antibodies are associated with pregnancy loss in women with the lupus anticoagulant

2006 ◽  
Vol 95 (05) ◽  
pp. 796-801 ◽  
Author(s):  
Thomas Sailer ◽  
Claudia Zoghlami ◽  
Christine Kurz ◽  
Helmut Rumpold ◽  
Peter Quehenberger ◽  
...  
Keyword(s):  
Lupus Anticoagulant ◽  
Pregnancy Loss ◽  
Fetal Loss ◽  
First Trimester ◽  
Normal Pregnancy ◽  
Cross Sectional Study ◽  
Anticardiolipin Antibodies ◽  
Cross Sectional ◽  
Glycoprotein I ◽  
Increased Risk

SummaryThe presence of lupus anticoagulant (LA) predisposes to fetal loss and to venous and arterial thrombosis; however, a subgroup of women is unaffected by pregnancy loss. Currently, no predictive markers are available for the identification of women positive for LA at increased risk for pregnancy loss. It was the aim of our study to investigate whether increased anti-β2-GPI-antibodies predict pregnancy loss in women positive for LA. We performed a cross-sectional study in a cohort of 39 women with persistent LA, who had in total 111 pregnancies. Fifteen women had exclusively normal pregnancies (30 pregnancies) and 24 women had pregnancy losses (81 pregnancies). Anti-β2-GPI-antibodies were determined using a semiquantitative enzyme linked immunoassay (QUANTA Lite™ β2 GPI IgG and IgM; Inova Diagnostics). Increased levels of anti-β2-GPI antibodies were significantly associated with pregnancy loss [odds ratio (OR) 9.6, 95% confidence interval (CI) 1.6 – 56.4].This risk was even higher in the subgroup of women (n=16) with more than two miscarriages or fetal loss after the first trimester [OR 13.1, 95% CI 1.4 – 126.3]. There was no significant association between anticardiolipin antibodies and pregnancy loss [OR 3.5, 95% CI 0.7 – 17.6].The coexistence of anti-β2-GPI and anticardiolipin antibodies was also predictive for pregnancy loss [OR 6.1, 95%CI 1.3 – 29.7]. Interestingly, the prevalence of thrombosis was similar between women with normal pregnancy (87%) and those with pregnancy loss (75%). We conclude that increased levels of anti-β2-GPI antibodies are predictive for pregnancy loss among women positive for LA, and that prophylactic treatment should be considered in these women even without a history of previous pregnancy loss.

scholarly journals Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study [see comments]

Blood ◽  
1992 ◽  
Vol 80 (4) ◽  
pp. 975-980
Author(s):  
JS Ginsberg ◽  
P Brill-Edwards ◽  
M Johnston ◽  
JA Denburg ◽  
M Andrew ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Pregnancy Loss ◽  
Anticardiolipin Antibody ◽  
Cross Sectional Study ◽  
Anticardiolipin Antibodies ◽  
Sectional Study ◽  
Cross Sectional ◽  
Previous Pregnancy

To determine whether an association exists between the presence of antiphospholipid antibodies and pregnancy loss, a cross-sectional study was performed. Consecutive women who were referred to three outpatient rheumatology clinics and who had systemic lupus erythematosus (SLE) and a history of one or more pregnancies were evaluated. Patients were interviewed to determine outcomes of all previous pregnancies. Blood was taken on two separate occasions at least 3 months apart to test for the presence of the lupus anticoagulant and anticardiolipin antibodies; on both occasions, five tests of the lupus anticoagulant, with well- defined normal ranges, and an enzyme-linked immunosorbent assay to measure IgG anticardiolipin antibodies were performed. Patients were considered to be positive for the lupus anticoagulant if one or more tests was abnormal on both occasions and positive for anticardiolipin antibodies if the test was abnormal on both occasions. Forty-two women were studied. Statistically significant associations were shown between lupus anticoagulant positivity and previous pregnancy loss (odds ratio [OR], 4.8; 95% confidence intervals [CI], 1.0 to 23.6; P = .05) and between anticardiolipin antibody positivity and previous pregnancy loss (OR, 20.0; 95% CI, 1.3 to 97.0; P = .01). All seven women with multiple episodes of pregnancy loss were lupus anticoagulant positive and four of these were also anticardiolipin antibody positive. If patients who are transiently positive for lupus anticoagulant and/or anticardiolipin antibodies are considered to be test positive, the associations with pregnancy loss are no longer statistically significant. Within the group of lupus anticoagulant-positive patients, we observed stronger associations between the presence of six or more positive tests and pregnancy loss than between the presence of two to five positive tests and pregnancy loss. No single test for the lupus anticoagulant provides a statistically significant association with pregnancy loss. The results of our study show that by performing multiple lupus anticoagulant tests and by repeating testing for lupus anticoagulant and anticardiolipin antibodies on more than one occasion, significant associations between the presence of antiphospholipid antibodies and previous pregnancy loss can be shown in patients with SLE.

scholarly journals Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study [see comments]

Blood ◽  
1992 ◽  
Vol 80 (4) ◽  
pp. 975-980 ◽  
Author(s):  
JS Ginsberg ◽  
P Brill-Edwards ◽  
M Johnston ◽  
JA Denburg ◽  
M Andrew ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Pregnancy Loss ◽  
Anticardiolipin Antibody ◽  
Cross Sectional Study ◽  
Anticardiolipin Antibodies ◽  
Sectional Study ◽  
Cross Sectional ◽  
Previous Pregnancy

Abstract To determine whether an association exists between the presence of antiphospholipid antibodies and pregnancy loss, a cross-sectional study was performed. Consecutive women who were referred to three outpatient rheumatology clinics and who had systemic lupus erythematosus (SLE) and a history of one or more pregnancies were evaluated. Patients were interviewed to determine outcomes of all previous pregnancies. Blood was taken on two separate occasions at least 3 months apart to test for the presence of the lupus anticoagulant and anticardiolipin antibodies; on both occasions, five tests of the lupus anticoagulant, with well- defined normal ranges, and an enzyme-linked immunosorbent assay to measure IgG anticardiolipin antibodies were performed. Patients were considered to be positive for the lupus anticoagulant if one or more tests was abnormal on both occasions and positive for anticardiolipin antibodies if the test was abnormal on both occasions. Forty-two women were studied. Statistically significant associations were shown between lupus anticoagulant positivity and previous pregnancy loss (odds ratio [OR], 4.8; 95% confidence intervals [CI], 1.0 to 23.6; P = .05) and between anticardiolipin antibody positivity and previous pregnancy loss (OR, 20.0; 95% CI, 1.3 to 97.0; P = .01). All seven women with multiple episodes of pregnancy loss were lupus anticoagulant positive and four of these were also anticardiolipin antibody positive. If patients who are transiently positive for lupus anticoagulant and/or anticardiolipin antibodies are considered to be test positive, the associations with pregnancy loss are no longer statistically significant. Within the group of lupus anticoagulant-positive patients, we observed stronger associations between the presence of six or more positive tests and pregnancy loss than between the presence of two to five positive tests and pregnancy loss. No single test for the lupus anticoagulant provides a statistically significant association with pregnancy loss. The results of our study show that by performing multiple lupus anticoagulant tests and by repeating testing for lupus anticoagulant and anticardiolipin antibodies on more than one occasion, significant associations between the presence of antiphospholipid antibodies and previous pregnancy loss can be shown in patients with SLE.

IgA Anticardiolipin Antibodies – Relation with other Antiphospholipid Antibodies and Clinical Significance

1998 ◽  
Vol 79 (02) ◽  
pp. 282-285 ◽  
Author(s):  
Josep Ordi-Ros ◽  
Francesc Monegal-Ferran ◽  
Nuria Martinez ◽  
Fina Cortes-Hernandez ◽  
Miquel Vilardell-Tarres ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Fetal Loss ◽  
Cross Sectional Study ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Serum Samples ◽  
Cross Sectional ◽  
Vein Thrombosis

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.

scholarly journals Detection of antitrophoblast antibodies in the sera of patients with anticardiolipin antibodies and fetal loss

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2730-2741 ◽  
Author(s):  
KR McCrae ◽  
AM DeMichele ◽  
P Pandhi ◽  
MJ Balsai ◽  
P Samuels ◽  
...  
Keyword(s):  
Fetal Loss ◽  
Thromboxane A2 ◽  
First Trimester ◽  
Anticardiolipin Antibodies ◽  
Trophoblast Cells ◽  
Fetal Demise ◽  
Blood Fluidity ◽  
Increased Risk ◽  
History Of ◽  
Placental Blood

Abstract Women with anticardiolipin antibodies (ACLA) are at increased risk for fetal loss. One potential explanation for this outcome is that sera from these individuals contain antibodies reactive with trophoblast cells, which are involved in the establishment of the uteroplacental vasculature and maintenance of placental blood fluidity. To examine this hypothesis, we compared the incidence of trophoblast-reactive antibodies in 27 patients with ACLA and a history of fetal loss with that in 29 normal pregnant women. Sera from 20 patients, but only one control, contained trophoblast-reactive antibodies (P < .001). These antibodies were not directed against major histocompatibility class I antigens, and reacted with both term and first-trimester trophoblast cells. In most cases, sera from which ACLA were adsorbed by cardiolipin- containing liposomes maintained reactivity against cells. In addition, patient Ig fractions immunoprecipitated an approximately 62-kD protein from the trophoblast cell surface, stimulated the release of arachidonic acid and thromboxane A2 by trophoblasts, and inhibited the binding of prourokinase to trophoblast urokinase receptors. These observations show that sera from women with ACLA and a history of fetal loss contain antitrophoblast antibodies. These antibodies may be serologically distinct from ACLA, and may contribute to the pathogenesis of fetal demise.

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.

scholarly journals Obstetric and neonatal outcome in women with a history of recurrent miscarriage at tertiary care hospital, Karnataka: a retrospective cross-sectional study

2018 ◽  
Vol 7 (2) ◽  
pp. 648 ◽  
Author(s):  
Chintan Upadhyay ◽  
Nisha Upadhyay
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Miscarriage ◽  
Tertiary Care ◽  
Previous History ◽  
Cross Sectional Study ◽  
Care Hospital ◽  
Sectional Study ◽  
Cross Sectional ◽  
Increased Risk ◽  
History Of

Background: When clinical pregnancy is established, the risk of spontaneous pregnancy loss is ~12-14%, and therefore the incidence of Recurrent Pregnancy Loss (RPL) by chance alone would be in the order of 0.35%. It occurs in 0.5-3% of women. The objective of this study was to evaluate the obstetric outcome in pregnancies with history of one or more abortions.Methods: It is a retrospective cross-sectional study done at Obstetrics and Gynecology Department, Dr. B. R. Ambedkar Medical College and Hospital, Bangalore. Record review of cases was done from January 2005 to December 2009. Inclusion criteria were pregnancies with history of previous abortions.Results: There were 400 cases with previous history of abortions. There were 266 (66.4%) booked cases while 134 (33.5%) were unbooked cases. 272 (68.0%) patients crossed viable period of pregnancy (more than 28 weeks). Around 56 (14.0%) cases had repeat abortions, 276 (69.0%) cases underwent vaginal delivery and 124 (31.0%) underwent cesarean section. Almost 91 (22.8%) of Babies were low birth weight while others were above 2.5 kg. There were 52 (13.0%) preterm babies and 28 (7.0%) Intrauterine demise of fetuses.Conclusions: Patients with previous history of abortions are at increased risk of adverse maternal and perinatal outcome.

scholarly journals Detection of antitrophoblast antibodies in the sera of patients with anticardiolipin antibodies and fetal loss

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2730-2741
Author(s):  
KR McCrae ◽  
AM DeMichele ◽  
P Pandhi ◽  
MJ Balsai ◽  
P Samuels ◽  
...  
Keyword(s):  
Fetal Loss ◽  
Thromboxane A2 ◽  
First Trimester ◽  
Anticardiolipin Antibodies ◽  
Trophoblast Cells ◽  
Fetal Demise ◽  
Blood Fluidity ◽  
Increased Risk ◽  
History Of ◽  
Placental Blood

Women with anticardiolipin antibodies (ACLA) are at increased risk for fetal loss. One potential explanation for this outcome is that sera from these individuals contain antibodies reactive with trophoblast cells, which are involved in the establishment of the uteroplacental vasculature and maintenance of placental blood fluidity. To examine this hypothesis, we compared the incidence of trophoblast-reactive antibodies in 27 patients with ACLA and a history of fetal loss with that in 29 normal pregnant women. Sera from 20 patients, but only one control, contained trophoblast-reactive antibodies (P < .001). These antibodies were not directed against major histocompatibility class I antigens, and reacted with both term and first-trimester trophoblast cells. In most cases, sera from which ACLA were adsorbed by cardiolipin- containing liposomes maintained reactivity against cells. In addition, patient Ig fractions immunoprecipitated an approximately 62-kD protein from the trophoblast cell surface, stimulated the release of arachidonic acid and thromboxane A2 by trophoblasts, and inhibited the binding of prourokinase to trophoblast urokinase receptors. These observations show that sera from women with ACLA and a history of fetal loss contain antitrophoblast antibodies. These antibodies may be serologically distinct from ACLA, and may contribute to the pathogenesis of fetal demise.

scholarly journals Causes of mid trimester pregnancy loss in a tertiary care hospital

2020 ◽  
Vol 3 (2) ◽  
pp. 64-69
Author(s):  
Bushra Zardad ◽  
Anisa Fawad ◽  
Ayesha Ismail ◽  
Shazia Mehreen ◽  
Sadia Bibi
Keyword(s):  
Pregnancy Loss ◽  
Tertiary Care ◽  
Relevant Information ◽  
Management Plan ◽  
Cross Sectional Study ◽  
Care Hospital ◽  
Second Trimester ◽  
Cross Sectional ◽  
Trimester Pregnancy ◽  
Increased Risk

Introduction: Mid trimester of pregnancy is relatively a safe time of pregnancy with minimal and no complications. Mid trimester pregnancy loss constitutes 1 to 5 % of total miscarriages. The purpose of this study is to evaluate the causes of second trimester miscarriages so as to improve the outcome in future pregnancies. Materials & Methods: This was a prospective cross-sectional study. Demographic features, relevant information and risk factors were recorded in a predesigned proforma. Detailed history was followed by thorough clinical examination and appropriate investigations were advised. Results: Total number of miscarriages admitted in the unit over the period of two years were 336 and among them 30 patients presented with second trimester miscarriages (8.9%). The mean age of the patients was 31.4 years. In 19 patients (63.4%) there were identifiable causes for the miscarriage. 7 patients (23.33%) had fibroids in the uterus, 5 patients (16.67%) had bacterial vaginosis, 4 patients (13.33%) had cervical incompetence and in 3 patients (10%) there were congenital abnormalities in the uterus. Conclusion: Patients with second trimester pregnancy loss are at significantly increased risk (10 times more likely) for recurrent second trimester loss. In 50 to 70% of patients no cause can be identified. After single loss there is 80% chance of successful pregnancy outcome in future. Even after two and three mid trimester losses still there is 60% chance of alive pregnancy next time, so thorough evaluation and management plan is needed to prevent this mishap in future pregnancies.

Protein Z in normal pregnancy

2005 ◽  
Vol 93 (04) ◽  
pp. 706-709 ◽  
Author(s):  
Ruth Stiller ◽  
Malgorzata Roos ◽  
Roland Zimmermann ◽  
Katharina Quack Loetscher
Keyword(s):  
First Trimester ◽  
Normal Pregnancy ◽  
Progressive Increase ◽  
Cross Sectional Study ◽  
Factor X ◽  
Clotting Factors ◽  
Protein Z ◽  
Cross Sectional ◽  
Fibrinolytic Proteins ◽  
Adverse Pregnancy

SummaryChanges in the coagulation and fibrinolytic systems during pregnancy lead to a higher risk of thromboembolism. These changes include the increase of many clotting factors, as well as a significant fall in activity of fibrinolytic proteins, such as protein C. Protein Z is a vitamin-K-dependent plasma glycoprotein and inhibits the activation of factor X by serving as a cofactor to a plasma proteinase inhibitor. Protein Z deficiency has recently been reported in women with unexplained early fetal losses, and antibodies to protein Z can contribute to adverse pregnancy outcomes. The aim of this study was to determine the range of protein Z in normal pregnancies at different gestational weeks in a cross-sectional and a longitudinal setting. In the longitudinal study we found a 20% increase (p=0.006) of protein Z from first trimester to delivery and a 30% decrease (p<0.0001) 6 to 12 weeks after delivery. In the cross-sectional study these findings were reproducible. In summary, our data show a progressive increase in protein Z levels with gestational age in normal pregnancies and a return to normal levels around 6 to 12 weeks postpartum. The normal increase of protein Z during pregnancy may balance the increase of clotting factors to protect pregnant women from thrombosis.

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