Clinical features of non-criteria obstetric antiphospholipid syndrome: a retrospective cohort study on antibody-based risk classification and pregnancy outcomes.

Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study

This guidance updates and replaces the previous guideline on the investigation and management of antiphospholipid syndrome (APS) published in 2000 (Greaves et al, 2000), though where there have not been changes we refer back to them when appropriate. The guidance is updated with reference to relevant publications since 2000. Publications known to the writing group were supplemented with additional papers identified by searching PubMed for publications in the last 11 years using the key words: lupus anticoagulant, anticardiolipin, antiphospholipid, b2–glycoprotein I, antiprothrombin and limits (clinical trial, randomized control trial, meta-analysis, humans, core clinical journals, English language). The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the Royal College of Obstetricians and Gynaecologists (RCOG), and the British Committee for Standards in Haematology (BCSH) Committee and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found at http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMEN DATION/43_GRADE.html. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of patients with antiphospholipid syndrome though individual patient circumstances may dictate an alternative approach.

Bloody mess

Association of thrombophilias in women with unexplained recurrent pregnancy loss (RPL)

The association between maternal thrombophilia and intrauterine growth restriction

Background: Bad obstetric history (BOH) implies previous unfavorable fetal outcome in terms of two or more consecutive spontaneous abortions, early neonatal deaths, stillbirths, intrauterine fetal deaths, intrauterine growth retardation and congenital anomalies. The immune factors associated with pregnancy loss are classified as autoimmune and alloimmune factors. The autoimmune factors include the synthesis of autoantibodies (anti-phospholipid antibodies, anti-nuclear antibodies, anti-thyroid antibodies). The main types of antiphospholipid antibodies are Lupus Anticoagulant (LA) and Anticardiolipin (aCL) antibodies (IgG & IgM).Objective: To measure the level of anticardiolipin antibodies in the sera of women with bad obstetric history.Patients & method: the study was conducted from October 2009 till June 2011 including 117 patients who attended private clinic & laboratory. Patients included in the sudy were those with history of two or more recurrent miscarriages, intrauterine fetal death & stillbirth. Fetal losses due to diabetes or congenital anomalies were excluded.Serum levels of anticardiolipin IgM & IgG antibodies were measured using AESKULISA phospholipid-Screen-GM (Germany) which is a solid phase enzyme immunassay for the separate qualitative & quantitative detection of IgG and /or IgM antibodies in human sera.Results: from the total of 117 patients with BOH fourteen (11.96%) had positive anticardiolipin antibodies in their sera. When comparing between the different groups of patient who were classified according to the type of fetal loss the highest number & percentage of positive anticardiolipin antibody were found in those with three & more recurrent miscarriages (4 cases, 57.14%). When comparing the IgM & IgG levels in different patients groups, the highest levels were found in those with three & more recurrent miscarriages.Conclusion: Anticardiolipin antibodies can have a positive association in women with bad obstetric history especially those with three & more recurrent miscarrigages. The level of IgM & IgG is highest in this group however these antibodies should be looked for in other patients with BOH

Objective Antiphospholipid syndrome (APS) is a chronic autoimmune disease with a high prevalence in females. Published data have identified pregnant women with APS may suffer from recurrent miscarriage, fetal death. However, the association between antiphospholipid antibody (aPL) and fetal growth restriction (FGR) remains controversial. This study aims to systematically review the literature on population-based studies investigating an association between aPL and FGR. Methods The literature was searched on 1 November, 2021, using Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), following the MOOSE checklist. Study inclusion criteria focused on peer-reviewed published articles that reported an association between aPL and FGR. Quality assessment was performed based on the Newcastle-Ottawa scale. The between-study heterogeneity was assessed by the Q test. Publication bias was assessed by funnel plots. Results Twenty-two studies (with 11745 pregnant women) were included in the final analysis. Pooled odds ratio for association of aPL, anticardiolipin antibodies (ACA), anti-beta2 glycoprotein 1 antibodies (β2GP1), and FGR was 1.26 (95%CI 1.12, 1.40), 2.25 (95%CI 1.55, 2.94), and 1.31 (95% CI 1.12, 1.49), respectively. Lupus anticoagulant (LA) did not increase the chance of FGR (OR 0.82, 95%CI 0.54, 1.10). Conclusions Our meta-analysis showed that aPL increased the risk of FGR. The risk of FGR varies with the aPL types. ACA and β2GP1 are strongly associated with FGR. There are currently insufficient data to support a significant relationship between LA and FGR.

Anticardiolipin antibodies (aCL) were found to recognize beta 2glycoprotein I (beta 2GPI) structure altered by its interaction with an oxygen modified solid phase surface by gamma-ray radiation. Lupus anticoagulant (LA) has been reported to comprise anti prothrombin antibodies, anti factor X antibodies and anti beta 2GPI antibodies. The present study focuses on the possible association between antibodies against the altered beta 2GPI structure (anti beta 2GPI antibodies) and LA in patients with recurrent pregnancy loss. Moreover, the clinical significance of both subgroups of so-called antiphospholipid antibodies were investigated to cast light on the controversy of whether aCL and LA are risk factors for pregnancy losses. One hundred and ninety five women with a history of two or more unexplained consecutive miscarriages and 100 control pregnant women were tested. Lupus anticoagulant was detected by the dilute phospholipid activated partial thromboplastin time. Anti beta 2GPI antibodies were measured by the ELISA method using commercially oxygenated microtiter plates. Twenty two (11.3%) and 19 (9.7%) of the 195 recurrent aborters were, respectively, positive for LA and anti beta 2GPI antibodies. Seven (3.6%) of the aborters had both of them. None of the control pregnant women had LA. Three of the control pregnant women had anti beta 2GPI antibodies. Nine (40.9%) of 22 aborters with positive-LA had a history of miscarriages in the second trimester as compared to 8 (4.6%) of 173 aborters with negative-LA. (P = 0.000007, Odds ratio = 14.3). None of the 12 aborters with anti beta 2GPI antibodies but no LA had a history of second trimester-fetal loss. These results support the hypothesis that aCL and LA define two distinct but partly related populations and that aCL include two subtypes of antibodies, with and without LA activity. LA and anti beta 2GPI antibodies appear to be associated with pregnancy loss, with LA being linked not only to abortions in the first trimester but also to miscarriages in the second trimester.

The Association Between Antiphospholipid Antibodies and Adverse Pregnancy Outcomes: A Metaanalysis.

Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome

Antiphospholipid syndrome is a chronic autoimmune disease with a high prevalence in females. Published data have identified that antiphospholipid antibodies (APLA) of antiphospholipid syndrome are risk factors for poor pregnancy outcomes, such as recurrent spontaneous abortion, intrauterine growth restriction and preeclampsia. However, the association between APLA and late fetal loss is not fully understood and remains controversial. The aim of this study is to identify and analyze the recent publications to better understand the association between APLA and late fetal loss. The literature was searched on 31 January 2019 using Ovid, Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) to evaluate the association between APLA and late fetal loss, with articles published before January 2019, according to the PRISMA statement. Without imposing regional restrictions, referenced articles were selected. Quality assessment was conducted independently by two reviewers, based on the Newcastle-Ottawa scale. For the meta-analysis, we used odds ratios (random effects model). The between-study heterogeneity was assessed by Q test. Publication bias was assessed by funnel plots. Nineteen studies (with 10265 cases) were included in the final analysis. The odds ratio (OR) for the late fetal loss with lupus anticoagulant was 5.02 (95% confidence interval [CI] 2.14-7.89). Seven included studies reported that lupus anticoagulant had a statistically significant association with late fetal loss. The results did not show a statistically significant association between anticardiolipin antibodies and late fetal loss. The pooled odds ratio for the association of anticardiolipin antibodies with late fetal loss was 3.47 (95% CI 0.68-6.26). However, we did find the relation between anticardiolipin antibodies and late fetal loss among cohort studies (OR 2.27, 95% CI 1.20-3.44). Anti-beta2 glycoprotein 1 antibodies (β2GP1) showed a significant association with late fetal loss (OR 3.13, 95% CI 0.75-5.50). Lupus anticoagulant is strongly associated with late fetal loss in antiphospholipid syndrome patients. However, the association between anticardiolipin antibodies and late fetal loss is inconsistent. There are currently insufficient data to support a significant relation between β2GP1 and late fetal loss.

Investigation of recurrent miscarriages

Guideline No. 442: Fetal Growth Restriction: Screening, Diagnosis, and Management in Singleton Pregnancies

Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which have been defined by varying laboratory test systems. Lupus anticoagulants (LA) and anticardiolipin antibodies (ACA) are the two most prominent members of this family of antibodies. LA are detected utilizing various phospholipid (PL) dependent tests of coagulation (e.g., activated partial thromboplastin time [APTT], Kaolin Clotting Time [KCT], dilute Russell Viper Venom Time [dRVVT]). Originally, LA were thought to be a laboratory nuisance since the vast majority of individuals with LA did not bleed. Paradoxically, patients with LA were found to have an increased incidence of thromboembolic events and also recurrent spontaneous abortions (RSA). Thus, the laboratory detection of LA has become part of the work up of patients with thromboembolic disorders and RSA. ACA are detected using solid phase assay systems (radioimmunoassay or ELISA). The presence of ACA has the same clinical implications as that of LA. Although originally it was suggested ACA and LA were the same antibody, it is now well accepted that they, in many instances, are different antibodies. Therefore, it is critical for laboratories to evaluate patient samples for both LA and ACA. In approximately 60% of circumstances, both antibodies will be found. In the remaining cases, there will be discordance between the two test systems. The question of whether APA are causative, coincidental, or a consequence of the clinical complications of RSA and thrombosis remains controversial. Recent evidence based on prospective clinical studies and analysis of markers of in vivo coagulation suggests APA are causative.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiphospholipid antibodies (lupus anticoagulans and anticardiolipine antibodies) are frequent cause of recurrent spontaneous abortion in patients with secondary sterility. Our aim was to evaluate the frequency of lupus anticoagulans antibodies in patients with recurrent abortions and to analyze their coagulation status relative to health (control) patients. We got the statistical significances (p < 0.05) in number of lupus anticoagulans positive women between the groups. Activated partial tromboplastin time and protrombin time are statistical significant (p < 0.05) higher in analyzed patients with recurrent abortion, which is in agreement of existing lupus anticoagulans activity. Detecting by the time, antiphospholipid antibodies and giving the anticoagulant therapy to the patients, the risk for abortion will be decreased.