Absence Of Antiphospholipid Syndrome Research Articles

Thyroid Peroxidase Antibodies and Prospective Live Birth Rate: A Cohort Study of Women with Recurrent Pregnancy Loss.

Background: Thyroid autoimmunity has been associated with pregnancy loss. Suggested mechanisms include thyroid function aberrations or an underlying breach of immunotolerance. We hypothesized that thyroid autoimmunity is a marker of the latter in women with recurrent pregnancy loss. This study investigated thyroid peroxidase antibody (TPOAb) status as a predictor of live birth in women with unexplained recurrent pregnancy loss. Methods: Cohort study of 825 consecutive women with recurrent pregnancy loss followed at the tertiary referral center for Recurrent Pregnancy Loss, Copenhagen University Hospital (Rigshospitalet), from 2011 to 2017. Recurrent pregnancy loss was defined as ≥3 consecutive losses, and as unexplained by absence of antiphospholipid syndrome, parental chromosome abnormality, or uterus malformation. Upon first visit, all women were screened for thyrotropin (TSH) and TPOAbs (TPOAb positivity: ≥60 kIU/L). Adjusted logistic regression analyses included as covariates the following: maternal age, TSH, previous number of losses, body mass index, smoking, pregnancy achieved by assisted reproductive technology, and thyroxine replacement (T4) treatment. Results: We included 825 women with a total of 3246 previous losses, of whom 139 (16.8%) were TPOAb positive. TPOAb positivity was not associated with the previous number of losses (p = 0.41). Women with unexplained recurrent pregnancy loss had a live birth rate in the first pregnancy after referral of 62.8% (285 of 454). TPOAb positivity was found in 78 of 454 (17.2%) women and was associated with a reduced live birth rate (51.3% vs. 65.2%, p = 0.02, adjusted odds ratio [aOR] 0.2 [0.1-0.6] p = 0.001). Treatment with T4 increased live birth rate significantly (aOR 3.7 [1.4-9.8], p = 0.007), and TPOAb-positive women receiving T4 had a live birth rate similar to that of TPOAb-negative women not receiving T4 (p = 0.70). Only 30% of TPOAb-positive women and 39% of women treated with T4 during pregnancy had known thyroid disease at referral. Conclusion: In a large cohort of women with unexplained recurrent pregnancy loss, TPOAb positivity was predictive of a reduced live birth rate. However, T4 treatment improved odds of live birth. The study supports screening for TPOAbs as a risk factor in women with unexplained recurrent pregnancy loss. The beneficial effect of T4 treatment in this high-risk group needs confirmation by randomized controlled trials. Close collaboration between fertility experts and endocrinologists is paramount.

Hormonal contraception in women with autoimmune diseases

Hormonal contraception represents the contraceptive method of choice for the majority of women aged between 15 and 44 from developing countries. The majority of autoimmune diseases especially rheumatologically ones as systemic lupus erythematosus (SLE) rheumatoid arthritis polymyositis or dermatomyositis scleroderma or Sjogren syndrome mainly affects the female population. Early counseling of these patients on the existing contraceptive methods is particularly important for several reasons: women with autoimmune diseases have the same infertility rate compared to healthy women; the treatments used for the basic disease can present adverse fetal effects; if pregnancy coincides with the disease remission the odds for a healthy pregnancy and devoid of adverse events increases. Women with autoimmune diseases have the same need to choose a safe and efficient contraceptive method just like general population. Physicians should fully understand the advantages and disadvantages of each contraceptive method the effect of various contraceptive methods in disease activity health risks and the possibility of interaction with other competing drugs as well as the couples preferences. Combined oral contraception is efficient convenient and reversible. These have indication in most of autoimmune pathologies including SLE outside of flares in the absence of antiphospholipid syndrome or other thrombotic risk factors. In this review we tried to summarize the instructions for using hormonal contraception by women at reproductive age affected by one of the main autoimmune diseases conditions with an important component in young female population.

Systemic lupus erythematosus and thrombosis.

Systemic Lupus Erythematosus (SLE) is an acquired, multiorgan, autoimmune disease. Clinical presentation is extremely variable and heterogeneous. It has been shown that SLE itself is an independent risk factor for developing both arterial and venous thrombotic events since SLE patients have an Odds Ratio (OR) for thrombosis that varies depending on the clinical and laboratory characteristics of each study cohort. The risk of developing a thrombotic event is higher in this setting than in the general population and may further increase when associated with other risk factors, or in the presence of inherited or acquired pro-thrombotic abnormalities, or trigger events. In particular, a striking increase in the number of thrombotic events was observed when SLE was associated with antiphospholipid antibodies (aPL). The presence of aPLs has been described in about 50% of SLE patients, while about 20% of antiphospholipid syndrome (APS) patients have SLE. While APS patients (with or without an autoimmune disease) have been widely studied in the last years, fewer studies are available for SLE patients and thrombosis in the absence of APS. Although the available literature undoubtedly shows that SLE patients have a greater prevalence of thrombotic events as compared to healthy subjects, it is difficult to obtain a definite result from these studies because in some cases the study cohort was too small, in others it is due to the varied characteristics of the study population, or because of the different (and very copious) laboratory assays and methods that were used. When an SLE patient develops a thrombotic event, it is of great clinical relevance since it is potentially life-threatening. Moreover, it worsens the quality of life and is a clinical challenge for the clinician.

Chorea associated with high titers of antiphospholipid antibodies in the absence of antiphospholipid antibody syndrome.

BackgroundChorea associated with high titers of antiphospholipid antibodies in the absence of antiphospholipid antibody syndrome has been seldom reported.Case reportAn 89-year-old female developed persistent right side chorea associated with high titers of anticardiolipin antibody (antiphospholipid antibosies immunoglobulin (Ig)M, 45 MPL and 112 IgM aCL (MPL) after 3 months) but normal lupus anticoagulants. Her magnetic resonance imaging (MRI) showed no abnormality, but positron emission tomography (PET) demonstrated increased bilateral striatal metabolic activity, more on the left side. Her MRI showed no cause for chorea. The PET scan demonstrated a marked increase in the metabolic activity of the left basal ganglia.DiscussionHer chorea remained unchanged over a 9-month follow-up period. The literature on chorea associated with high titers of antiphospholipid antibodies in the absence of antiphospholipid syndrome is reviewed.

Non-thromboembolic risk in systemic lupus erythematosus associated with antiphospholipid syndrome.

We investigated the impact of secondary antiphospholipid syndrome (APS) and antiphospholipid antibody (aPL) positivity on the non-thromboembolic clinical manifestations of systemic lupus erythematosus (SLE). In total, 224 patients with SLE were studied, of whom 105 were aPL-positive; 52 fulfilled the criteria for APS. SLE- and APS-related clinical and laboratory features were assesed: SLE patients with aPL or APS were compared with those without these features. Not only thromboembolic events, but also Coombs-positive haemolytic anaemia, thrombocytopenia and endocarditis occurred significantly more frequently in the aPL-positive than in the aPL-negative patients. In the APS + SLE subgroup, several non-thromboembolic symptoms occurred more often than in the absence of APS: pleuritis, interstitial lung disease, myocarditis, nephritis and organic brain syndrome. The mean number of major organ manifestations (1.2 vs. 0.5) and the overall number of organ manifestations (8.1 vs. 6.9) were higher in the APS + SLE patients than in those without APS (p < 0.05). The APS + SLE subgroup more frequently required intensive immunosuppressive treatment than did the APS-negative patients (p < 0.05). SLE patients with aPL positivity or secondary APS also have a higher risk to develop non-thromboembolic disease manifestations in addition to the aPL-related symptoms, and are predisposed to more severe SLE manifestations.

The involvement of CD36 in monocyte activation by antiphospholipid antibodies

CD36, known as a scavenger receptor, is a transmembrane glycoprotein expressed on monocytes, platelets and endothelial cells, recognizes multiple ligands, including phosphatidylserine, and regulates atherogenesis and thrombosis. The objective of this study is to investigate the possible involvement of CD36 in the pathophysiology of thrombosis in patients with antiphospholipid syndrome (APS). First, rs3765187, a missense mutation linked to CD36 deficiency, was investigated by TaqMan polymerase chain reaction (PCR) genotyping method in 819 Japanese, including 132 patients with APS, 265 with systemic lupus erythematosus (SLE) in the absence of APS, and 422 healthy subjects. Then, the involvement of CD36 in antiphospholipid antibody (aPL)-induced tissue factor (TF) expression was examined using CD36-null mice or anti-CD36. Purified IgG from patients with APS and a monoclonal phosphatidylserine-dependent antiprothrombin antibody were used in these experiments. TF expression was tested by real-time PCR and flow cytometry. Minor allele carrier of rs3765187 was less frequent in patients with APS (3.8% p=0.032), but not in patients with SLE in the absence of APS (7.9% p=0.32), compared with healthy subjects (10.2%). The aPL-induced TF expression was significantly suppressed on peritoneal macrophages from CD36-null mice compared to wild type and significantly inhibited by anti-CD36 on human monocytes. The gene mutation linked to CD36 deficiency was less frequent in patients with APS. The deficient or suppressed CD36 function significantly reduced aPL-induced TF expression in vitro. Taken together, in a susceptible background CD36 scavenger receptor function may be involved in the thrombotic pathophysiology in patients with APS.

Aspirin and Aspirin Combined with Low-Molecular-Weight Heparin in Women with Unexplained Recurrent Miscarriage: a Randomized Controlled Multicenter Trial (ALIFE Study).

Abstract 488▪▪This icon denotes an abstract that is clinically relevant. BackgroundUnexplained recurrent miscarriage (RM) is extremely stressful for women and effective treatment is eagerly awaited. Aspirin and (low-molecular-weight) heparin are being used increasingly, even though evidence to support its use is not availabel. The aim of the ALIFE study was to investigate whether aspirin alone or combined with low-molecular-weight heparin, compared to placebo, improved the live birth rate in women with unexplained RM. MethodsWe conducted a multicenter, randomized, controlled trial in 8 centers in The Netherlands. Women aged between 18 and 42 years were eligible if they were diagnosed with unexplained RM and attempted to conceive or were less than 6 weeks pregnant. RM was defined as at least 2 miscarriages with an upper gestational age of 20 weeks (calculated from the first day of the last menstrual period). Unexplained RM was diagnosed in case of normal parental karyotype, the absence of uterine pathology on pelvic ultrasound, absence of antiphospholipid syndrome (lupus anticoagulant and anticardiolipin IgG and IgM), and a normal fasting level of homocysteine (< 16 μmol/L). Exclusion criteria were previous venous or arterial thromboembolism, indication for anticoagulant treatment during pregnancy or endocrine disorders.After written informed consent was obtained, randomization was performed centrally with stratification for age (< or ≥36 years), number of previous miscarriages (2 or ≥3), and center.Oral medication was started at the day of inclusion. Aspirin was given as calcium carbasalate 100 mg (Ascal®, Vemedia BV, Diemen, The Netherlands), equivalent to 80 mg of acetylsalicylic acid. Aspirin and placebo study medication was packed in sachets of identical appearance. Patients, doctors, and trial nurses were blinded for these treatment allocations. Women allocated to receive open-label nadroparin 2850 IU s.c. received oral aspirin and started nadroparin injections when a viable intrauterine pregnancy was confirmed by ultrasound from 6 weeks of gestational age. Aspirin or placebo was given until 36 weeks of gestational age or stopped at time of miscarriage, ectopic pregnancy or premature delivery. LMWH was given throughout gestation and stopped 12 hours before delivery.The primary outcome measure was live birth rate. Secondary outcomes included miscarriage rate, uterine and umbilical blood flow profile and prevalence of obstetric complications. Differences in live birth rates will be expressed as relative risks and 95% confidence intervals with the placebo group as reference. Data were analyzed according to the intention-to-treat principle. Preliminary resultsBetween February 2004 and January 2008, 364 women were included in the trial. On July 1st 2009, 25 were not pregnant 2 years after inclusion, 16 were not pregnant, 8 were pregnant, 26 women had decided to withdraw from the study, and 3 had been included erroneously. The results presented in this abstract are based on a pre-scheduled interim analysis of 281 women who had reached an endpoint (live birth or miscarriage) on July 1st 2009.AspirinAspirin and nadroparinPlacebon=95n=91n=95Live birth, n (%)64 (67.4)65 (71.4)67 (70.5)Relative risk (95%CI)0.96 (0.79-1.16)1.01 (0.84-1.22)1 (reference)The live birth rate did not differ between women assigned to aspirin, aspirin combined with nadroparin, and placebo. The Data Safety Monitoring Board advised the Steering Committee of the ALIFE study that further continuation of the study was futile. At the time of submission of this abstract, the database is being finalized, with closure scheduled on October 1st 2009. We will present definite data, including those of the a priori defined subgroup of women with hereditary thrombophilia, at the ASH meeting in December 2009. ConclusionsAspirin, and aspirin combined with nadroparin did not improve the live birth rate in women with unexplained RM (Current Controlled Trial number, ISRCTN58496168).Funding: ZonMW, the Dutch Organization for Health Research and Development (945-27-003). Vemedia BV supplied study medication (calcium carbasalate and placebo). GlaxoSmithKline BV offered a grant. Funding sources were not involved in study protocol preparation, trial management or data analysis. Disclosures:Off Label Use: Calcium carbasalate (equivalent to acetyl salicylic acid) and nadroparin to prevent recurrent miscarriage.. Buller:GSK: Consultancy, Honoraria, Research Funding. Middeldorp:GSK: Consultancy, Honoraria, Research Funding.

Chorea associated with antiphospholipid antibodies in a patient with Kabuki syndrome

Kabuki syndrome, OMIM 147920 (KS) is a disorder characterized by multi-system abnormalities. These include physical, neurological, endocrine, and autoimmune abnormalities. Multiple autoimmune abnormalities are described in KS such as immune thrombocytopenic purpura (ITP), vitiligo, thyroiditis, hemolytic anemia, and hypogammaglobulinemia. In this report, we describe a patient with KS with sudden onset chorea associated with the presence of anti-phospholipid antibodies (aPLs) in the serum. Chorea in the presence of aPLs has been well described in the literature both in the presence and absence of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). This report of APL in a patient with KS adds to the list of autoimmune disorders seen in patients with KS and also strengthens the hypothesis that patients with this syndrome have an increased incidence of immune dysregulation.