Annals Express: Antiphospholipid and Antioangiogenic Activity in Women with Recurrent Miscarriage and Antiphospholipid Syndrome (original) (raw)
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Role of antiphospholipid antibodies in recurrent pregnancy loss
International journal of clinical obstetrics and gynaecology, 2020
Antiphospholipid syndrome is associated with a hallmark of Obstetric complications including recurrent miscarriage, early delivery, oligohydramnios, prematurity, intrauterine growth restriction, fetal distress, fetal or neonatal thrombosis, pre-eclampsia/eclampsia, HELLP syndrome, arterial or venous thrombosis and placental insufficiency. Antiphospholipid antibodies promote activation of endothelial cells, monocytes and platelets, causing an overproduction of tissue factor and thromboxane A2. These factors lead to a hypercoagable state leading to various obstetric complications. The aim of this study was to evaluate the prevalence of anti-phospholipid antibodies in patients with RPL and to evaluate the relation of antibody positivity with other parameters.
Role of Antiphospholipid Antibodies in Unexplained Recurrent Abortion and Intrauterine Fetal Death
2013
Background: Women with antiphospholipid antibodies (aPL) have a significant risk of reproductive failure and adverse pregnancy outcomes, the recurrent miscarriages, intrauterine fetal deaths, and intrauterine fetal growth restriction is significant among these patients. Women with a history of recurrent abortion and unexplained fetal death or a history of recurrent thrombotic episodes should be screened for the presence of antiphospholipid antibodies. We studied the incidence of anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) factor in recurrent unexplained miscarriages and intrauterine fetal deaths. Subjects and Methods: We performed a cohort study among women who attended the department of Obstetrics and Gynecology, Assiut University hospitals, Assiut, Egypt, between October 2007 and October 2011 after being referred due to recurrent miscarriage (≥ 2 consecutive pregnancy losses). All women underwent a standardized investigation sequence. Women with other reasons for...
Archives of pathology & laboratory medicine, 2005
Anti-phospholipid antibodies (aPL) are a heterogeneous group of autoantibodies, the presence of which is associated with thrombotic events and miscarriage. To establish whether antibodies directed against phospholipid-binding plasma proteins such as beta(2)-glycoprotein I (beta(2)GPI), prothrombin (PT), and annexin V (Anx V) constitute a risk factor for thromboembolism in patients with systemic lupus erythematosus (SLE) and for miscarriage in women with recurrent pregnancy loss (RPL), independently of the presence of the classic anticardiolipin (aCL) antibodies, and whether their determination together with that of aCL would help to increase the diagnostic sensitivity of aPL tests. The prevalence of various antibodies directed toward phospholipids (CL and other anionic phospholipids [APL]) and phospholipid-binding proteins (beta(2)GPI, PT, and Anx V) was determined by immunoenzymatic methods in 311 serum samples. Twenty-five patients with aCL-positive primary anti-phospholipid syndr...
Antiphospholipid antibodies and the investigation of recurrent miscarriage
Current Obstetrics & Gynaecology, 1999
Recurrent miscarriage (three or more consecutive miscarriages) affects 1% of the female population and this causes severe psychological morbidity in both the sufferer and their partner. For many years the aetiology of recurrent miscarriage in the majority of cases has remained unclear. Treatment regimens to improve pregnancy outcome were based on poorly-designed studies, often without control cohorts, which have subsequently been shown to be of no proven benefit. Over the past 15 years accumulating evidence has implicated the presence of antiphospholipid antibodies (APAbs) in the aetiology of recurrent miscarriage. APAbs can be found in 15% of the recurrent miscarriage population, and are associated with first and second-trimester miscarriages as well as other obstetric complications. Aspirin and subcutaneous heparin administration are of clinically-proven benefit in lowering the miscarriage rate in women with this condition. Maternal side effects of aspirin and heparin are rare but include thrombocytopenia and osteoporosis. No direct teratogenic effects of aspirin and heparin have been demonstrated but pregnancies complicated by APAbs need to be monitored closely for evidence of pre-eclampsia and intrauterine growth restriction.
Obstetrics & Gynecology, 2003
To examine whether there are characteristic histological features in placentas from ongoing pregnancies of patients with a history of recurrent miscarriage, with and without primary antiphospholipid antibody syndrome, in relation to clinical pregnancy outcome. METHODS: Patients attending a recurrent miscarriage clinic were investigated and treated according to an established protocol. One hundred twenty-one consecutive patients achieving a potentially viable pregnancy (at least 24 completed weeks' gestation), including 60 primary antiphospholipid antibody syndrome-positive cases and 61 primary antiphospholipid antibody syndrome-negative cases were included. After delivery, placental pathologic examination was carried out by a pathologist unaware of the clinical details. Histological sections were examined by two pathologists independently. Pregnancy outcome and placental findings were reviewed in relation to the maternal antiphospholipid antibody status. RESULTS: Pregnancy outcome was similar in primary antiphospholipid antibody syndrome-positive and primary antiphospholipid antibody syndrome-negative groups regarding gestation at delivery and antepartum obstetric complications. Several histological placental abnormalities were identified in both groups, but most pregnancies were clinically uncomplicated, with no significant placental abnormalities. In cases with pregnancy complications, the placental pathology was primarily that of uteroplacental vasculopathy, such as placental infarction and preeclampsia, but there were no specific placental lesions or patterns of abnormalities characteristic of primary antiphospholipid antibody syndrome-positive patients. A small subgroup of primary antiphospholipid antibody syndromepositive patients may be at increased risk of development of maternal floor infarction or massive perivillus fibrin deposition. CONCLUSION: There are no specific histopathologic placental abnormalities characteristic of treated patients with antiphospholipid antibody syndrome and poor reproductive history, but complications of uteroplacental disease are more common.
Antiphospholipid antibodies among women experiencing fetal loss
PubMed, 2013
The presence of antiphospholipid antibodies (aPLs) is closely associated with thrombotic events and pregnancy complications such as recurrent pregnancy loss, preeclampsia and placental insufficiency. We investigated the presence of aPLs and its frequency among female patients with a history of fetal loss in a Malaysia population. Serum samples were collected from 108 patients who had (1) one or more unexplained deaths of morphologically normal fetuses at or beyond the 22nd week of gestation, or (2) one or more premature births of morphologically normal neonates at or before the 24th week of gestation due to eclampsia or preeclampsia, or recognized features of placental insufficiency, or (3) three or more unexplained, consecutive, spontaneous miscarriages before the 20th week of gestation. Serum was tested for aPLs subtypes: anticardiolipin (aCL), anti-beta-2- glycoprotein I (aβ2GPI), anti-beta-2-glycoprotein I dependent cardiolipin (aβ2GPI dependent CL), anti-phosphatidylcholine (aPC), anti-phosphatidylethanolamine (aPE), anti-phosphatidylinositol (aPI), anti-phosphatidylserine (aPS) and anti-sphingomyeline (aSph) by using the enzyme-linked immunosorbent assay (ELISA) method. The mean age of patients was 30±5. Four patients (3.7%) were found positive for at least one aPLs subtype. Four aPLs subtypes were detected. The most common subtypes was aβ2GPI dependent CL (3.7%), followed by aCL (2.7%), aβ2GPI (0.9%), and aPE(0.9%). In conclusion, frequency of aPLs among women with fetal loss (3.7%) in Malaysia was low with subtype aβ2GPI dependent CL being the most prevalent aPLs.
Updating on the Pathogenic Mechanisms 5 of the Antiphospholipid Antibodies-Associated Pregnancy Loss
Clinical Reviews in Allergy & Immunology, 2008
Anti-phospholipid antibodies (aPL) are risk factor for recurrent pregnancy loss and obstetrical complications. The mechanisms of aPL-mediated pregnancy failure are still a matter of research. Although aPL are associated with thrombosis, thrombotic events cannot explain all the miscarriages. There is evidence for a direct in vitro aPL effect on the trophoblast as shown by their binding; reduction of proliferation, human chorionic gonadotrophin release, in vitro invasiveness, adhesion molecule expression; and increased apoptosis. Such a direct reactivity is supported by the expression of beta2 glycoprotein (β2GP) I on trophoblast cell membranes. aPL/anti-β2GPI antibodies also bind to human decidual/endometrial cells in vitro and induce a pro-inflammatory phenotype. APL-mediated inflammatory processes at the placental level are apparently responsible for fetal loss at least in animal models. Both complement activation and pro-inflammatory cytokine/chemokine secretion have been shown to play a role. More recently, complement-induced tissue factor expression on infiltrating neutrophils was described as an additional pathogenic mechanisms mediated by aPL. As a whole, these findings do suggest that aPL may induce a defective placentation by acting at different levels without involving necessarily thrombotic events.
Obstetric and vascular antiphospholipid syndrome: same antibodies but different diseases?
Recurrent thrombosis and miscarriages are the main clinical manifestations of antiphospholipid syndrome (APS). Although most patients display both clinical signs, some patients can have isolated vascular or obstetric variants. Emerging data raise the question of whether obstetric and vascular APS are the same or different diseases. An important difference between the two conditions is that a thrombophilic state is a common feature in vascular APS, whereas clot occlusions of the decidual spiral arteries are seldom observed in obstetric APS, and infarctions are found in only one-third of APS placentae. Conversely, inflammation, which is undetectable in vascular APS, is frequently observed in the placentae of patients with obstetric APS and has been documented in the placentae of pregnant mice with fetal loss mediated by antiphospholipid antibodies. Attempts to identify different antibodies or epitopes responsible for the two clinical manifestations of APS have so far been unsuccessful. Possible mechanisms exist that might explain the development of the two clinical presentations, including the tissue distribution and expression level of the main target antigen of antiphospholipid antibodies, β2 glycoprotein I (β2GPI). The identification of the factors that promote the onset of either obstetric or vascular APS has important diagnostic and therapeutic implications.
The association of antiphospholipid antibodies with intrauterine fetal death: A case–control study
Thrombosis Research, 2012
Introduction: Over the past few decades it has been recognized that antiphospholipid antibodies are associated with pregnancy loss. Other placenta-mediated pregnancy complications have also been associated with the presence of antiphospholipid antibodies. Most studies have measured antiphospholipid antibodies near the time of the event investigated. Objectives: To investigate the association of antiphospholipid antibodies and a history of intrauterine fetal death (IUFD) in a case-control design. Materials and methods: A case-control study of 105 women with a history of IUFD after 22 gestational weeks and 262 controls with live births. The prevalence of lupus anticoagulant, anticardiolipin-and anti-β2glycoprotein 1 antibodies were measured 3-18 years after the event of IUFD. Results: Total 9.5% of women with a history of IUFD and 5.0% of controls had at least one positive test for antiphospholipid antibodies (OR 2.0; 95% confidence interval (CI) 0.9-4.8). Women with a history of IUFD were significantly more often positive for lupus anticoagulant compared to controls (OR 4.3; 95% CI 1.0-18.4). The association of lupus anticoagulant with a history of IUFD was confined to women positive for other antiphospholipid antibodies in addition to lupus anticoagulant. Being positive for anti-β2-glycoprotein 1 or anticardiolipin antibodies alone was not significantly associated with a history of IUFD. Conclusions: Women with a history of IUFD after 22 gestational weeks were more often lupus anticoagulant positive. The association was confined to women with multiple positivity for antiphospholipid antibodies, although firm conclusions on the importance of multiple positivity cannot be made from this study.
Down-regulation of maternal antiphospholipid antibodies during early pregnancy and pregnancy outcome
American Journal of Obstetrics and Gynecology, 1994
OBJECTIVE: We investigated the hypothesis that maternal autoimmune responses to phospholipid antigens measured before and during pregnancy are not related to successful pregnancy outcome. STUDY DESIGN: One hundred twenty-three women with recurrent spontaneous abortions were serially tested for antiphospholipid antibodies during their pregnancies. RESULTS: In 72 women with recurrent spontaneous abortions and without anti phospholipid antibodies before the pregnancy, the incidence of antiphospholipid antibody production at the time of pregnancy termination was significantly higher in those who miscarried the index pregnancy than those who were delivered of a live-born infant. In 51 anti phospholipid antibody-positive women with recurrent spontaneous abortions there were dramatic increases in titers of anticardiolipin antibody and antiphosphatidylserine antibody in those who miscarried the index pregnancy (p < 0.005). In women who were delivered of a live-born infant, the titers remained stable or decreased during pregnancy. CONCLUSIONS: Down-regulation of anti phospholipid antibody production during early pregnancy is associated with favorable pregnancy outcome. (AM J OSSlEl GYNECOL 1994; 171 :239-46.) Antiphospholipid antibodies are associated with a history of recurrent spontaneous abortion and thrombosis in women without autoimmune diseases. I -3 Testing for, quantitating, and associating antiphospholipid antibodies with a specific disorder of reproduction is a rapidly developing field. The predictive value of antiphospholipid antibodies for a subsequent pregnancy loss or thrombotic episode ranges from 48% to 76%. 1.3.4 When antiphospholipid antibodies are present during pregnancy, there are complications of thrombosis, preeclampsia, fetal distress, preterm delivery, or intrauterine growth retardation. 5 • 6 However, the optimal treatment for autoimmune-associated reproductive loss is not yet defined.