Antiphospholipid Antibodies in a General Obstetric Population: Clinical Impact on Pregnancy Outcome and Relationship with the M2 Haplotype in the Annexin A5 (ANXA5) Gene

2018 ◽  
Vol 39 (02) ◽  
pp. 203-207
Author(s):  
Michela Villani ◽  
Donatella Colaizzo ◽  
Pasquale Martinelli ◽  
Filomena Cappucci ◽  
Lucia Fischetti ◽  
...  
Keyword(s):  
Risk Factors ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Clinical Impact ◽  
Obstetric Complications ◽  
Obstetric Outcomes ◽  
P Value ◽  
Annexin A5 ◽  
Glycoprotein I ◽  
Obstetric Population

AbstractAntiphospholipid (aPL) antibodies are recognised risk factors for adverse obstetric outcomes. Recently, carriers of the M2 haplotype in the Annexin A5 gene have been shown to have a higher susceptibility to develop aPL antibodies. In a general obstetric population, we prospectively evaluated the possible relationship between: (1) aPL antibodies and M2 haplotype; and (2) aPL antibodies and/or M2 haplotype and obstetric outcomes. From a cohort of 3,097 consecutive pregnant women, 1,286 samples were analysed for the presence of both anti-cardiolipin and anti-human β2-glycoprotein I antibodies; samples with available DNA (n = 606) were also investigated for the M2 haplotype. Overall, 41/1,286 (3.2%) women showed the presence of aPL antibodies. Among them, 2 (4.8%) experienced a pregnancy loss and 38 (92.7%) gave birth to live-born babies (p-value = non-significant vs. those without aPL antibodies). M2 haplotype was identified in 140 (23.1%) out of 606 women with DNA available: 3/140 (2.1%) M2 carriers and 17/466 (3.6%) non-carriers tested positive for aPL antibodies, respectively (p-value = non-significant). In total, 15/150 (10%) M2 and/or aPL antibody carriers, and 38/445 (8.5%) non-aPL antibody and/or M2 carriers suffered from obstetric complications, respectively (p-value = non-significant). No relationship between aPL antibodies and M2 haplotype was found. Furthermore, neither aPL antibodies nor the M2 haplotype is associated with obstetric complications.

Prevalence of antiphospholipid antibodies and risk of subsequent adverse obstetric outcomes in women with prior pregnancy loss

2015 ◽  
Vol 107 ◽  
pp. 59-63 ◽  
Author(s):  
Zachary S. Bowman ◽  
Vera Wünsche ◽  
T. Flint Porter ◽  
Robert M. Silver ◽  
D. Ware Branch
Keyword(s):  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Obstetric Outcomes

Correlation between antiphospholipid antibodies that recognize domain I of β2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1490-1494 ◽  
Author(s):  
Bas de Laat ◽  
Xiao-Xuan Wu ◽  
Menno van Lummel ◽  
Ronald H. W. M. Derksen ◽  
Philip G. de Groot ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Anticoagulant Activity ◽  
Annexin A5 ◽  
Anionic Phospholipids ◽  
Glycoprotein I ◽  
Group A ◽  
Group B ◽  
Domain I ◽  
American Authors

Abstract The paradoxical correlation between thrombosis and the lupus anticoagulant (LAC) effect is an enigmatic feature of the antiphospholipid (aPL) syndrome. The Dutch authors previously reported that thrombosis-related anti–β2-glycoprotein I (β2GPI) antibodies recognize domain I and cause LAC. The American authors reported that aPLs disrupt an anticoagulant annexin A5 (AnxA5) crystal shield. We investigated whether antidomain I antibodies correlate with disruption of AnxA5-anticoagulant activity. We studied a well-characterized group of 33 patients including subgroups with β2GPI-dependent LAC that recognize domain I (n = 11), with β2GPI-independent LAC (n = 12), and lacking LAC (n = 10). The effects on AnxA5-anticoagulant activity were determined with an AnxA5 resistance assay that measures coagulation times with and without AnxA5. Patients with β2GPI-dependent LAC (group A, all with thrombosis) had significantly lower AnxA5-anticoagulant ratios than those with β2GPI-independent LAC (group B, thrombosis n = 4; 157.8% versus 235.6%, P < .001) and those without LAC (group C, thrombosis n = 2; 157.8% versus 232.5%, P < .001). There was no difference in the ratios between groups B and C (P = .92). Plasmas with β2GPI-dependent LAC that recognize domain I displayed significantly increased AnxA5 resistance, suggesting that specifically anti-β2GPI antibodies compete with AnxA5 for anionic phospholipids. These results are consistent with a model in which aPL antibodies may promote thrombosis by interfering with the anticoagulant activity of AnxA5.

Paternal and maternal carriage of the annexin A5 M2 haplotype are equal risk factors for recurrent pregnancy loss: a pilot study

2012 ◽  
Vol 98 (2) ◽  
pp. 383-388 ◽  
Author(s):  
Nina Rogenhofer ◽  
Laura Engels ◽  
Nadja Bogdanova ◽  
Frank Tüttelmann ◽  
Arseni Markoff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pilot Study ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Annexin A5

P-058: Antiphospholipid antibodies and M2 haplotype in annexin A5 gene: possible relationship and clinical impact on feto-maternal outcome

2017 ◽  
Vol 151 ◽  
pp. S128
Author(s):  
M. Villani ◽  
E. Chinni ◽  
G.L. Tiscia ◽  
F. Cappucci ◽  
L. Fischetti ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Clinical Impact ◽  
Maternal Outcome ◽  
Annexin A5

scholarly journals Anti-Phosphatidylserine/Prothrombin Antibodies in Healthy Women with Unexplained Recurrent Pregnancy Loss

2021 ◽  
Vol 10 (10) ◽  
pp. 2094
Author(s):  
Daniel E. Pleguezuelo ◽  
Oscar Cabrera-Marante ◽  
Magdalena Abad ◽  
Edgard Alfonso Rodriguez-Frias ◽  
Laura Naranjo ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Odds Ratio ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Fetal Death ◽  
Fetal Loss ◽  
Healthy Women ◽  
Glycoprotein I ◽  
Early Miscarriage ◽  
Beta 2

Recurrent pregnancy loss (RPL) affects up to 6% of couples. Although chromosomal aberrations of the embryos are considered the leading cause, 50% of cases remain unexplained. Antiphospholipid Syndrome is a known cause in a few cases. Antiphospholipid antibodies (aPL) anticardiolipin, anti-Beta-2-Glycoprotein-I and Lupus Anticoagulant (criteria aPL) are recommended studies in RPL workup. We tested healthy women with unexplained RPL for criteria aPL and anti-Phosphatidylserine/Prothrombin antibodies (aPS/PT). Patients were classified into three groups according to the number and pregnancy week of RPL: Extra-Criteria (EC), with 2 miscarriages, Early Miscarriage (EM), with ≥3 before pregnancy at week 10 and Fetal Loss (FL), with ≥1 fetal death from pregnancy at week 10. Circulating criteria aPL were absent in 98.1% of EM, 90.9% of FL and 96.6% of EC groups. In contrast, aPS/PT were positive in 15.4% of EM, 15.1% of FL, 16.6% of EC patients and 2.9% in controls. aPS/PT posed a risk for RPL, with an odds ratio of 5.96 (95% confidence interval (CI): 1.85–19.13. p = 0.002) for EM, 7.28 (95% CI: 2.07–25.56. p = 0.002) for FL and 6.56. (95% CI: 1.77–24.29. p = 0.004) for EC. A successful live birth was achieved in all pregnant patients positive for aPS/PT who received treatment with heparin, aspirin and/or hydroxychloroquine.

scholarly journals Autoimmunity to the Lung Protective Phospholipid-Binding Protein Annexin A2 Predicts Mortality Among Hospitalized COVID-19 Patients

2021 ◽  
Author(s):  
Marisol Zuniga ◽  
Claudia Gomes ◽  
Steven E. Carsons ◽  
Michael T. Bender ◽  
Paolo Cotzia ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Binding Protein ◽  
Clinical Findings ◽  
Annexin A2 ◽  
P Value ◽  
Annexin A5 ◽  
Potential Mechanism ◽  
Membrane Stabilization ◽  
Phospholipid Binding ◽  
Antibody Levels

ABSTRACTBackgroundAnnexin A2 is a phospholipid-binding protein involved in fibrinolysis, cell membrane stabilization and repair, and ensuring the integrity of the pulmonary microvasculature. Given the autoantibodies observed in COVID-19 and that Annexin A2 is a known target of antiphospholipid antibodies, we studied autoimmunity directed against Annexin A2 among hospitalized COVID-19 patients.MethodsWe used ELISA to identify the levels of IgG autoantibodies recognizing Annexin A2 and A5 among 86 hospitalized cases of COVID-19. Using logistic regression, we analyzed the association between anti-Annexin A2 and A5 antibody levels with mortality after adjusting for age, sex, race and key comorbidities.ResultsWe found higher average levels of anti-Annexin A2 antibodies among hospitalized COVID-19 patients that died when compared with non-critical hospitalized COVID-19 patients (p-value = 0.006) and critically ill COVID-19 patients (p-value = 0.04). No significant differences in anti-Annexin A5 antibody levels were identified. Regression analysis showed that anti-Annexin A2 antibody levels as measured in relative units strongly predicted mortality with an odds ratio of 9.3 (95% CI: 1.9 to 44.6, p=0.005). In contrast, anti-Annexin A5 antibody levels were not associated with higher mortality (95% CI: 0.5 to 15.2, p=0.22).ConclusionsWe determined that anti-Annexin A2 antibodies were elevated among hospitalized COVID-19 patients and these levels predicted mortality. It is known that inhibition of Annexin A2 induces systemic thrombosis, cell death, and non-cardiogenic pulmonary edema. Autoimmunity to Annexin A2 is a potential mechanism that may explain the key clinical findings of severe COVID-19.

Relationship of Anti β2-giycoprotein I and Anti Prothrombin Antibodies to Thrombosis and Pregnancy Loss in Patients with Antiphospholipid Antibodies

1997 ◽  
Vol 78 (03) ◽  
pp. 1008-1014 ◽  
Author(s):  
Ricardo R Forastiero ◽  
Marta E Martinuzzo ◽  
Graciela S Cerrato ◽  
Lucía C Kordich ◽  
Luis O Carreras
Keyword(s):  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Univariate Analysis ◽  
Clinical Importance ◽  
Anticardiolipin Antibodies ◽  
Glycoprotein I ◽  
History Of ◽  
Risk For Thrombosis ◽  
Relationship Of

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.

scholarly journals Study of pregnancy outcome of threatened abortion and its correlation with risk factors in a tertiary care hospital of Mumbai, India

2018 ◽  
Vol 7 (11) ◽  
pp. 4598
Author(s):  
Dipali S. Sivasane ◽  
Rekha G. Daver
Keyword(s):  
Risk Factors ◽  
Maternal Age ◽  
Pregnancy Loss ◽  
Demographic Data ◽  
Tertiary Care ◽  
P Value ◽  
Care Hospital ◽  
Number Of Patients ◽  
Significant Difference ◽  
Threatened Abortion

Background: Early pregnancy loss is very common and, in most cases, it can be considered as nature’s method to select for a genetically normal offspring. Threatened abortion is a relatively common complication during pregnancy, occurring in approximately 20% of all pregnancies. Maternal age, Outcome of previous pregnancies, health of mother, any infection etc can be decisive factors in the risk of pregnancy loss.Methods: The present study was a cross sectional study where patients admitted with threatened abortion were interviewed using pretested semi-structured questionnaire after the treatment. Outcome of pregnancy was recorded. Their basic socio-demographic data along with possible risk factors were recorded. TORCH Ig M and Ig G were done in all patients.Results: Out of 95 patients admitted with threatened abortion, 42 (44%) patients undergone abortion whereas in 53 (56%) patients, pregnancy was continued. Out of total 60 patients admitted with the complain of only vaginal spotting, in 39 pregnancy continued and in 21 patients pregnancy was aborted. (p-value<0.05). 50.52% were from age group of 21 to 25 years of age. It was also seen that after 35 years of age, significant number of patients aborted. Out of these 11 patients with high BMI, pregnancy was continued only one patient. Out of total 20 patients positive for IgM of toxoplasma infection, pregnancy was aborted in 13 (65%) patients. Out of total 15 patients positive for IgM of cytomegalo virus infection, pregnancy was continued in 11 (73.3%) patients.Conclusions: Patients of threatened abortion with only symptom of spotting per vagina have good chances of continuation of the pregnancy. Increased maternal age above 35, Overweight and bad obstetric history are also associated with pregnancy loss. Though there was no statistically significant difference it was evident that among all TORCH infections, IgM toxoplasma and Rubella are associated more with pregnancy loss.

scholarly journals Risk Factors for the Development of the Disease in Antiphospholipid Antibodies Carriers: A Long-term Follow-up Study

2021 ◽  
Author(s):  
Rosalía Demetrio Pablo ◽  
Pedro Muñoz Cacho ◽  
Marcos López-Hoyos ◽  
Vanesa Calvo-Río ◽  
Leyre Riancho-Zarrabeitia ◽  
...  
Keyword(s):  
Risk Factors ◽  
Antiphospholipid Antibodies ◽  
Prophylactic Treatment ◽  
Primary Prophylaxis ◽  
Obstetric Complications ◽  
Clinical Criteria ◽  
Long Term Follow Up ◽  
Potential Risk Factors ◽  
Independent Risk Factors

AbstractThe natural history of antiphospholipid antibodies (aPL) carriers is not well-established. The objectives of the present study were (a) to study the probability of developing clinical criteria of antiphospholipid syndrome (APS), (b) to identify potential risk factors for developing thrombosis and/or obstetric complications, (c) to study the association between the antibody profile and development of APS, and (d) to determine the efficacy of primary prophylaxis. We retrospectively analyzed 138 subjects with positive aPL who did not fulfill clinical criteria for APS. The mean follow-up time was 138 ± 63.0 months. Thirteen patients (9.4%) developed thrombosis after an average period of 73.0 ± 48.0 months. Independent risk factors for thrombosis were smoking, hypertension, thrombocytopenia, and triple aPL positivity. Low-dose acetyl salicylic acid did not prevent thrombotic events. A total of 28 obstetric complications were detected in 92 pregnancies. During the follow-up, only two women developed obstetric APS. Prophylactic treatment in pregnant women was associated with a better outcome in the prevention of early abortions. The thrombosis rate in patients with positive aPL who do not meet diagnostic criteria for APS is 0.82/100 patients-year. Smoking, hypertension, thrombocytopenia, and the aPL profile are independent risk factors for the development of thrombosis in aPL carriers. Although the incidence of obstetric complications in this population is high (31.6%), only a few of them meet APS criteria. In these women, prophylactic treatment might be effective in preventing early abortions.

Central Nervous System Infections

2016 ◽  
pp. 453-460
Author(s):  
Pritish K. Tosh ◽  
M. Rizwan Sohail
Keyword(s):  
Risk Factors ◽  
Central Nervous System ◽  
Nervous System ◽  
Venous Thromboembolism ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Lupus Anticoagulant ◽  
Anticardiolipin Antibodies ◽  
Central Nervous System Infections ◽  
Glycoprotein I

Thrombophilia refers to the tendency for thromboembolism (ie, having risk factors for thromboembolism), which may be inherited or acquired. The presence of increasing numbers of risk factors further increases the risk of venous thromboembolism (VTE). Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, and anti–β‎2-glycoprotein I antibodies) and hyperhomocysteinemia are risk factors not only for VTE but also for arterial thrombosis.

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