Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin.

OBJECTIVE: To study the obstetric course of women with a history of recurrent miscarriage associated with antiphospholipid antibodies, lupus anticoagulant and anticardiolipin antibodies, treated with low dose aspirin and low dose heparin. DESIGN: Prospective observational study. SETTING: University based tertiary referral clinic. POPULATION: One hundred and fifty pregnant women with a history of recurrent miscarriage associated with persistently positive tests for antiphospholipid antibodies. METHODS: Lupus anticoagulant was detected using the dilute Russell's viper venom time together with a platelet neutralisation procedure. IgG and IgM anticardiolipin antibodies were detected using a standardised enzyme linked immunosorbent assay. An IgG anticardiolipin level > or = 5 per litre units and an IgM anticardiolipin level > or = 3 per litre units was considered positive. Aspirin (75 mg daily) was commenced at the time of a positive pregnancy test and heparin (5000 units subcutaneously 12 hourly, or enoxaparin 20 mg daily) was started when fetal heart activity was demonstrated on ultrasound. Treatment was stopped at the time of miscarriage or at 34 weeks of gestation. RESULTS: One hundred and seven pregnancies (71%) resulted in a live birth. Forty-one pregnancies (27%) miscarried, the majority in the first trimester. One woman had a stillbirth, and one a premature baby who died in the neonatal period. One pregnancy was terminated for a fetal anomaly. Gestational hypertension complicated 17% (18/108) of ongoing pregnancies and antepartum haemorrhage 7% (8/108). Twenty-six babies (24%) were delivered before 37 weeks of gestation. Fifty women (46%) were delivered by caesarean section. The median birthweight of all live born infants was 3069 g (range 531-4300); however 15% (16/108) of the infants were small for gestational age. CONCLUSION: Combination treatment with aspirin and heparin leads to a high live birth rate among women with recurrent miscarriage and antiphospholipid antibodies. However, successful pregnancies are prone to a high risk of complications during all trimesters. Close antenatal surveillance and planned delivery of these pregnancies in a unit with specialist obstetric and neonatal intensive care facilities are indicated.     

Plasmapheresis and pregnancy outcome in patients with antiphospholipid syndrome.

OBJECTIVE: To assess plasmapheresis with low dose prednisone on obstetric and neonatal outcomes among unsuccessfully treated pregnant women with documented antiphospholipid syndrome (APS). METHODS: Eighteen pregnant women received prednisone (10 mg/day) and plasmapheresis at 7.08+/-0.6 weeks of gestation, for 3 sessions per week, until lupus anticoagulant activity suppressed and IgG anticardiolipin lowered. Serial pulsatility indexes (PI) of umbilical and uterine arteries were performed. RESULTS: The live birth rate was 100%; mild pre-eclampsia 5.5%; preterm deliveries 22.22%; intrauterine growth restriction 11.11%; thrombocytopenia 5.5%; oligohydramnios and fetal distress 16.6%. There were no perinatal deaths, thrombotic events or lupus flare. Uterine artery PI was reduced and umbilical artery PI was >95th percentile. CONCLUSION: Plasmapheresis and low dose prednisone were associated with a low rate of obstetric and neonatal complications. Plasmapheresis may be used to treat pregnant women with documented APS when first lines (aspirin and/or heparin) fail to prevent pregnancy loss.     

Autoimmunity and pregnancy loss

Clinicians have recognized for several decades that certain autoimmune conditions, such as systemic lupus erythematosus (SLE), are associated with pregnancy loss. During the 1980s, investigations focused attention on fetal wastage in women with antiphospholipid antibodies and the antiphospholipid antibody syndrome (APS) was characterized. Its defining features include fetal wastage in the presence of significant levels of anticardiolipin antibodies. Since that time, interest in other autoimmune diatheses and various specific autoantibodies as possible causes of pregnancy loss has increased. Investigators have attempted to establish an association between recurrent pregnancy loss and the presence of a specific autoantibody or patterns of autoantibodies. Thus far, only modest evidence supports the concept that other autoantibodies are linked to, much less cause, pregnancy loss. In this review, we will define pregnancy loss in its various forms and discuss pregnancy loss in well-characterized autoimmune diseases such as SLE and APS. We will focus on the diagnosis and management of these conditions in women attempting to achieve successful pregnancies. Later we discuss the evidence concerning the less well defined association of antiphospholipid antibodies other than the lupus anticoagulant and anticardiolipin antibodies to recurrent pregnancy loss. We then outline the significance of antinuclear antibodies and antithyroid antibodies pertaining to adverse pregnancy outcome and conclude by summarizing and making some suggestions for further study.     

The significance of antiphospholipid antibodies in pregnant women with chronic hypertension

The objective of this study was to perform antiphospholipid antibody screening in women with chronic hypertension to assess whether the presence of such antibodies is associated with adverse pregnancy outcome. Serum for anticardiolipin antibodies and lupus anticoagulant was obtained in pregnant women with chronic hypertension who had no other indications for such testing. The primary outcomes of interest were the development of superimposed preeclampsia, preterm delivery, and fetal growth restriction. Only 8 (9%) of the 87 women enrolled tested positive (> 95th percentile) for anticardiolipin immunoglobulin G. None tested positive for lupus anticoagulant. The presence of antiphospholipid antibodies was not associated with adverse pregnancy outcome. We were unable to demonstrate that screening for antiphospholipid antibodies is a useful clinical practice in women whose only pregnancy complication was chronic hypertension. The significance of such antibodies in this particular group of patients can only be resolved with a large multicenter study.     

Antiphospholipid Antibodies in Pregnancy

We assessed the relationship between antiphospholipid antibodies and recurrent miscarriage, fetal deaths, and the pregnancy complications--placental abruption, fetal growth retardation and preeclampsia. The subjects were 81 women with a history of 3 or more miscarriages, 62 with a history of fetal death in the index pregnancy, 105 with a poor obstetric history or pregnancy complications and 13 with systemic lupus erythematosus. Antiphospholipid antibodies were found in 41% of women with a history of recurrent miscarriages, 29% with a history of recent intermediate fetal death or stillbirth, 19% with a poor obstetric history and 69% with systemic lupus erythematosus. There is a high incidence of antiphospholipid antibodies in complicated pregnancies. Patients presenting with the above pregnancy disorders should be tested for antiphospholipid antibodies because of the risk conferred on a fetus by their presence and to expand the treatment options.     

Acquired thrombophilias and pregnancy

Acquired thrombophilias are hypercoagulable states secondary to various aetiologies. In particular, during pregnancy the risks are exaggerated due to the underlying physiological changes. The commonest cause of acquired thrombophilia in pregnancy is antiphospholipid syndrome. Antiphospholipid syndrome (APS) is a complex multisystem disorder that has been associated with varied medical and obstetric complications. The pathogenesis of APS has been further elucidated in recent studies. The two most clinically significant antiphospholipid antibodies that are associated with recurrent pregnancy loss and thromboembolism are anticardiolipin antibodies (aCL) and lupus anticoagulant (LA). The laboratory diagnosis is based on the presence of moderate to high positive aCL and/or LA antibodies. It is crucial that APS is not inappropriately diagnosed as this has implications for counselling and management with thromboprophylaxis during pregnancy. Over the last decade there have been significant changes in the laboratory and clinical criteria for the diagnosis of APS. National and international collaborations have made efforts to standardize the laboratory methods. There have been very few randomized placebo-controlled trials of drug therapy and so not all drug treatment strategies have a strong evidence base. With current management strategies, using low-molecular-weight heparin and aspirin, a greater than 70% live birth rate may be achieved in affected pregnancies. A multidisciplinary approach in the management of these women is vital.     

Immunoglobulin A anti-beta2-glycoprotein antibodies in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death

OBJECTIVE: Studies in rheumatologic populations suggest that immunoglobulin A antiphospholipid antibodies are strongly associated with the clinical manifestations of antiphospholipid syndrome. However, the association between immunoglobulin A antiphospholipid antibodies and pregnancy loss is uncertain. We determined whether immunoglobulin A antiphospholipid antibodies, specifically anti-beta(2)-glycoprotein I and anticardiolipin, are associated with the obstetric features of antiphospholipid syndrome. STUDY DESIGN: Sera from 4 groups of women were studied: (1) 133 women who experienced unexplained recurrent spontaneous abortion, (2) 48 women who experienced unexplained fetal death, (3) 145 healthy fertile control subjects, and (4) 67 women with well-characterized antiphospholipid syndrome. Serum immunoglobulin A, immunoglobulin G, and immunoglobulin M anti-beta(2)-glycoprotein I and anticardiolipin antibodies were determined by enzyme-linked immunoassay. RESULTS: Groups of women who experienced unexplained recurrent spontaneous abortion and unexplained fetal death had a higher proportion of women who had positive test results for immunoglobulin A anti-beta(2)-glycoprotein I antibodies than fertile control subjects (P < .01, chi-square test); these subjects also had higher levels of autoantibody (P = .001, Kruskal-Wallis). Women who experienced recurrent spontaneous abortion had a higher proportion of women with positive test results for immunoglobulin A anticardiolipin antibodies compared to fertile control subjects (P < .05, chi-square test); this group also had higher levels of autoantibody (P = .0065, Kruskal-Wallis test). Linear regression analysis showed significant correlation between anti-beta(2)-glycoprotein I immunoglobulin A and anti-beta(2)-glycoprotein I immunoglobulin G (R = .609; P =.0001) and less correlation between anticardiolipin immunoglobulin A and anticardiolipin immunoglobulin G (R = .093; P = .065). CONCLUSION: Immunoglobulin A anti-beta(2)-glycoprotein I antibodies are more common in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death whose initial test results are negative for lupus anticoagulant and immunoglobulin G anticardiolipin antibodies compared to fertile control subjects. Therefore, these antibodies may identify additional women with clinical features of antiphospholipid syndrome who are not identified through traditional testing. It is unclear whether these antibodies are directly pathogenic, a result of the pregnancy losses, or markers for an underlying, yet uncharacterized autoimmune disorder.     

The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population

Circulating antibodies to negatively-charged phospholipids have been implicated in the genesis of adverse pregnancy outcomes. However, it has yet to be established that these antibodies are causative or that they are invariably associated with untoward perinatal outcomes. To address this issue, the prevalence of lupus anticoagulant and anticardiolipin antibodies was recorded in a low-risk obstetric population, and the outcome of untreated pregnancies were evaluated. Two of 737 patients (0.27%) had lupus anticoagulant documented by a prolonged activated partial thromboplastin time that did not correct this mixing studies. In comparison, greatly elevated concentrations of immunoglobulin M-anticardiolipin antibodies or immunoglobulin G-anticardiolipin antibodies were identified in 16/737 (2.2%) patients by means of an enzyme-linked immunosorbent assay. Spontaneous abortions occurred in both lupus anticoagulant-positive patients, suggesting that the activated partial thromboplastin time used was a relatively insensitive but specific marker for antiphospholipid antibody-associated adverse pregnancy outcomes. In contrast, although 12 of 16 anticardiolipin antibodies-positive pregnancies were complicated by perinatal loss, preterm delivery, or fetal growth retardation, four patients had uncomplicated pregnancies. Moreover, the distribution of anticardiolipin antibodies concentrations in these four patients was not clustered among the lowest anticardiolipin antibodies values, and anticardiolipin antibodies concentrations correlated weakly with adverse outcomes. These findings suggest that antiphospholipid antibodies are related to adverse pregnancy outcomes in a complex fashion and that therapy is not always required for acceptable outcomes in patients without other risk factors.     

The prevalence of autoantibodies during third-trimester pregnancy complicated by hypertension or idiopathic fetal growth retardation.

Lupus anticoagulant, anticardiolipin, antinuclear, anti-deoxyribonucleic acid, antithyroglobulin, and antithyroid microsomal antibodies were assayed during third-trimester pregnancy (100 normal, 100 with complications). In spite of a normal activated partial thromboplastin time in all instances, lupus anticoagulant was further investigated by three additional procedures: tissue thromboplastin inhibition time, platelet neutralization procedure, and cephalin neutralization test. The prevalence of autoantibodies in pregnancies with hypertension reaches 16% (four with lupus anticoagulant, two with anticardiolipin, and two with antithyroid microsomal antibodies), which is significantly greater than that for idiopathic fetal growth retardation (2%) (one with lupus anticoagulant antibodies) and normal pregnancies (3%) (two with antithyroglobulin and one with autithyroid microsomal antibodies) (p less than 0.01). Autoantibodies were equally distributed between patients with gestational hypertension and those with preeclampsia. When compared with the 42 patients with hypertension and no autoantibodies, the eight patients with autoantibody had a more frequent history of fetal growth retardation (p less than 0.05), but there was no difference in the severity of hypertension, the frequency of obstetric complications, or the outcome of pregnancy. They did not require any specific treatment.     

Antiphospholipid Antibody Syndrome in Pregnancy

Objective: to provide an overview of the clinical significance of antiphospholipid antibodies (APLA) in pregnancy, dealing mainly with the diagnosis and management of patients with this disorder.Data Sources: sources were identified from a MEDLINE search of English language articles published from 1985 to 1995 (Keywords: lupus anticoagulant, anticardiolipin antibodies, antiphospholipid antibodies, and antiphospholipid antibody syndrome). Additional sources were identified from references cited in relevant research articles.Methods of Study Selection: thirty-six articles where selected, including publications that recorded the prevalence of commonly described antiphospholipid antibodies, clinical significance, laboratory testing, and management of pregnant women with this disorder. Almost all articles were based on case series, meta-analysis, and prospective trial. Management protocol was based on the findings and recommendations of prospective trials and clinical reviews.Results: lupus anticoagulant (LA) and anticardiolipin (ACL) antibodies belong to a heterogeneous group of antibodies directed against protein epitopes that form complexes with negatively charged phospholipids. The selected studies were reviewed critically and their conclusions were evaluated; the available literature indicates that these antiphospholipid antibodies are frequently found at low levels in otherwise healthy people. At higher levels, the presence of these antibodies is closely associated with the occurrence of arterial and venous thromboembolism, thrombocytopaenia, fetal loss, and a variety of other conditions in patients with and without systemic lupus erythematosus (SLE). This combination of significant antiphospholipid antibody levels with certain clinical sequelae defines the presence of antiphospholipid antibody syndrome (APLAS).Conclusions: screening for antiphospholipid antibodies in the prenatal population seems unwarranted. If investigations of women at risk for APLAS are positive, close maternal and fetal surveillance are required. Prophylactic treatment might be used in this select group of patients, although optimal therapy has yet to be defined. Even though knowledge of APLAS pathophysiology is limited, it is currently the guide to treatment options. All prenatal patients with APLAS should receive low dose acetylsalicylic acid (ASA) and either heparin or steroids. Heparin is suggested if there is a history of thrombosis or placental infarction, while steroids should be considered if APLAS is secondary to SLE, or if there is previous evidence of inflammation and complement activation. Defining optimal therapy will require a large multicentre prospective trial. A detailed management protocol is proposed.     

The association of antiphospholipid antibodies with pregnancies complicated by fetal growth restriction

The association of antiphospholipid antibodies with fetal growth restriction is often cited, but the published evidence for this is based on few patients and comes primarily from patient histories, not study groups. In this prospective study, we evaluated a subgroup of our population with fetuses whose estimated weights at ultrasound were at or below the tenth percentile for gestational age. Plasma and serum testing was performed to determine the presence of antiphospholipid antibodies, specifically lupus anticoagulant and anticardiolipin antibodies, respectively. From March 1990 through March 1991, 55 women were followed for suspected fetal growth restriction. Intensive monitoring of the fetal condition and modification of the mother's activity were recommended, resulting in 100% compliance. Despite this, 37 newborns were confirmed by birth weight to be at or below the tenth percentile, and all were below the 45th percentile. Fifteen of 55 women (27%) were positive for anticardiolipin antibodies, as were nine of 37 (24%) with correctly diagnosed fetal growth restriction. Five of 15 women whose newborns had ponderal indexes below the tenth percentile tested positive for anticardiolipin antibodies. None of the women had a positive lupus anticoagulant test. The prevalence of anticardiolipin antibodies in this study group was significantly higher than in our general population. We conclude that there is a statistically significant association between the presence of circulating maternal anticardiolipin antibodies and fetal growth restriction.     

Treatment outcome in women suffering from recurrent miscarriages and antiphospholipid syndrome

OBJECTIVE: To evaluate the outcomes of treatment in patients suffering from recurrent spontaneous abortion and antiphospholipid syndrome. MATERIALS AND METHODS: 148 observed women suffering from recurrent abortion with presence of lupus anticoagulant antibodies (LA) and/or high moderate concentration of anticardiolipin antibodies (ACA) have been divided randomly into followed three treated groups: I--56 patients treated by low-dose of acetylsalicylic acid (LDA, 75 mg daily); II--39 patients treated by low molecular weight heparin (applied in dose of 20 g daily); III--53 patients treated by LDA and low molecular weight heparin simultaneously. RESULTS: It has been affirmed that coincidental application of low-dose of acetylsalicylic acid and low molecular weight heparin statistically more often increase the percentage of successful pregnancy in comparison with application of low molecular weight heparin or acetylsalicylic acid alone. In the group where only low-dose of acetylsalicylic acid was applied the success of pregnancy equaled 89.3%, in the group where only low molecular weight heparin was applied the successful pregnancy equaled 81.1% and in the group with acetylsalicylic acid and low molecular weight heparin being applied together the successful pregnancy equaled 92.5%. In has simultaneously been affirmed that the percentage of pregnancy loss is statistically higher in the women suffering from isolated occurrence of lupus anticoagulant antibodies (21.2%) in comparison with the women suffering from occurrence of anticardiolipin antibodies (6.7%) and anticardiolipin antibodies with lupus anticoagulant antibodies simultaneously. CONCLUSION: 1. Simultaneous application of low-doses of acetylsalicylic acid and low molecular weight heparin seems to be the best solution in patients suffering from recurrent spontaneous abortion and antiphospholipid syndrome. 2. The occurrence of anticardiolipin antibodies in the serum of blood in patients suffering from antiphospholipid syndrome is a better foretelling factor for the future pregnancy outcome than the occurrence of lupus anticoagulant antibodies.     

Lupus and pregnancy

Systemic lupus erythematosus (SLE) disproportionately affects women in their reproductive age years. Pregnancy in this systemic autoimmune disease has long been associated with poor obstetric outcomes. However, the frequency of pregnancy loss in lupus has dropped to a level commensurate with that of the general US population. The outcomes of lupus pregnancies are better if conception is delayed until the disease has been inactive for at least 6 months, and the medication regimen has been adjusted in advance. Pregnancy in lupus is prone to complications, including flares of disease activity during pregnancy or in the postpartum period, preeclampsia, miscarriage, stillbirth, intrauterine growth retardation, and preterm birth. Active lupus nephritis poses the greatest risk. The recognition of a lupus flare during pregnancy may be difficult because the signs and symptoms may mimic those of normal pregnancy. Monitoring should include baseline and monthly laboratory tests, serial ultrasonography, fetal surveillance tests, and fetal m-mode echocardiography for mothers with SS-A (Ro) or SS-B (La) antibodies. In the absence of any signs or symptoms of active SLE, affected patients require no specific treatment during pregnancy. If hydroxychloroquine was in use before conception, it should be maintained throughout pregnancy. If a woman with SLE has antiphospholipid antibodies, prophylactic treatment with aspirin and/or low-molecular weight heparin is indicated to prevent fetal loss. Lupus flares during pregnancy are generally treated with hydroxychloroquine, low-dose prednisone, pulse intravenous methylprednisolone, and azathioprine. High-dose prednisone and cyclophosphamide are reserved for severe lupus complications but are associated with significant pregnancy-related complications and poor obstetrical outcomes.     

Antiphospholipid antibodies and recurrent pregnancy loss: correlation between the activated partial thromboplastin time and antibodies against phosphatidylserine and cardiolipin

Concordance was determined among the presence of the lupus anticoagulant measured by prolongation of the activated partial thromboplastin time and IgG and IgM antibodies against phosphatidylserine and cardiolipin in 47 patients selected for study because of histories of recurrent spontaneous pregnancy loss and a positive test for at least one antiphospholipid antibody. Forty-five of 47 patients (96%) had a prolonged activated partial thromboplastin time, ranging from 46 to 150 seconds. Elevated levels of IgG antiphosphatidylserine antibodies and IgM antiphosphatidylserine antibodies were present in 41 (87%) and in 19 (40%) of samples, respectively. Antibodies against cardiolipin were less commonly observed; IgG anticardiolipin antibodies in only 32 (68%) of 47 samples and IgM anticardiolipin antibodies in 15 (36%) of 42 samples. Neither the level of IgG antiphosphatidylserine antibodies nor the level of IgG anticardiolipin antibodies correlated well with the degree of prolongation of coagulation in the activated partial thromboplastin time (R = 0.312, p = 0.032 for IgG antiphosphatidylserine antibodies versus activated partial thromboplastin time; R = 0.251, p = 0.088 for IgG anticardiolipin antibodies versus activated partial thromboplastin time). Concordance with the activated partial thromboplastin time, however, was observed in 41 (87%) samples for IgG antiphosphatidylserine antibodies and in only 32 (68%) samples for IgG anticardiolipin antibodies. Our conclusion is that the antiphosphatidylserine assay correlates best, although not totally, with the presence of lupus anticoagulant and that the antiphosphatidylserine assay is more sensitive than testing for anticardiolipin.     

Antiphospohlipid syndrome in obstetrics

Antiphospholipid syndrome is characterised by a variety of clinical and immunological manifestations. The clinical hallmarks of this syndrome are thrombosis and poor obstetric outcomes, including miscarriages, fetal loss and severe pre-eclampsia. The main antiphospholipid antibodies include lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I. The combination of aspirin and heparin is considered the standard of care for women with antiphospholipid syndrome and embryo-fetal losses; however, aspirin in monotherapy may have a place in women with recurrent early miscarriage. A good benefit-risk ratio of low-molecular-weight heparin in pregnancy thrombosis treatment has been reported. Warfarin must be avoided if possible throughout the first trimester of pregnancy. Adequate pregnancy management of women with antiphospholipid syndrome should include co-ordinated medical-obstetrical care, a close follow-up protocol and a good neonatal unit. Close blood pressure control and early detection of proteinuria, together with Doppler studies of the utero-placental circulation should be included in the management protocol.     

Pregnancy Loss with Phospholipid Antibodies: Improved Outcome with Aspirin Containing Treatment

Summary: The obstetric outcome in 37 patients with antiphospholipid antibodies (APAs) is described. The APAs were measured by the lupus anticoagulant assay and/or more recently anticardiolipin antibodies. There were 15 patients with SLE who without therapy had 51/58 pregnancy failures, either abortion or fetal death in utero, a failure rate of 88%. Likewise, 22 patients without definite SLE lost 69/87 pregnancies, a failure rate of 79%. After treatment the pregnancy wastage rate was 55% and 25% in the 2 groups respectively. When treatment regimens used were examined in detail the improvement with therapy was most clearly evident in the group who received low dose aspirin (75–150mg) in association with immunosup-pression. This improvement was most apparent in the patients without definite SLE.     

Pregnancy and Systemic Lupus Erythematosus

As SLE onset is often in young adulthood, pregnancy is common and is usually successful. Pregnancy, though, is considered high-risk due to a combination of maternal (lupus flare, diabetes, pre-eclampsia) and fetal (miscarriage, intrauterine fetal demise, preterm birth, intrauterine growth restriction, congenital heart block) risks.Pregnancy should be planned for a time of good control of SLE (on allowable medications). The antimalarial hydroxychloroquine should be continued. The only permitted immunosuppressive drugs are azathioprine and tacrolimus.Of the antiphospholipid antibodies, only the lupus anticoagulant has been associated with adverse pregnancy outcomes in the largest prospective multicenter study, Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus (PROMISSE). Management of antiphospholipid syndrome in pregnancy is low molecular weight heparin and aspirin, although only 75% of pregnancies are successful.     

Maternal and fetal complications associating lupus anticoagulant and its management; three case reports

Both lupus anticoagulant and anticardiolipin antibody are groups of antiphospholipid antibodies associated with high frequency of thrombosis, fetal loss and thrombocytopenia. The hall marks of their identification is the prolongation of phospholipid-dependant coagulation tests. Much is written in literature about the successful management of lupus anticoagulant during pregnancy, via corticosteroid and acetyl salicylic acid (Aspirin) therapy; however, up to now only little has been mentioned about maternal and fetal complications associating lupus anticoagulant and its management. Here we present three cases with significant complications among patients with lupus anticoagulant managed in Sint Augustinus Hospital over the last 3 years. These complications were secondary to antiphospholipid syndrome or to therapy. Maternal complications included gastritis, atrophy of quadriceps muscle, resistant premature contractions and pre-eclampsia. One of our patients developed small lymphocytic lymphoma 1 year after her last labour. Fetal complications included: prematurity, suprarenal insufficiency (temporary) and delayed neuromuscular development found at the 2 year follow-up. As far as we know, some of these complications have never been mentioned in literature.     

Pregnancy outcome is not affected by antiphospholipid antibody status in women referred for in vitro fertilization

OBJECTIVE: To determine the prevalence of antiphospholipid (aPL) and anti-beta 2 glycoprotein I (anti-beta2-GPI) antibodies in women referred for IVF and to prospectively evaluate the effect of these antibodies on IVF outcome. DESIGN: Prospective observational study. SETTING: A university hospital and IVF unit. PATIENT(s): Three hundred eighty consecutive women referred for IVF. INTERVENTION(s): Blood samples taken before commencement of IVF cycles were tested for the presence of aPL (lupus anticoagulant [LA], anticardiolipin [aCL], and antiphosphatidyl serine antibodies [aPS]) and anti-beta2-GPI antibodies. MAIN OUTCOME MEASURE(s): Antibody prevalence, pregnancy rates, and live birth rates. RESULT(s): Of the total 380 women, 89 tested persistently positive for aPL (23.4%). None of 176 women tested for IgG aPS antibodies had a positive titer. Only 3.3% (11 of 329) tested positive for anti-beta2-GPI antibodies. Pregnancy rate, live birth rate, gestational age at delivery, and birth weight were not affected by aPL status. CONCLUSION(s): Although women referred for IVF have a high prevalence of aPL, these antibodies do not affect the outcome of treatment. Screening women undergoing IVF for aPL is not justified.     

Obstetric performance in patients with the lupus anticoagulant and/or anticardiolipin antibodies.

Antiphospholipid antibodies, notably the lupus anticoagulant and anticardiolipin antibodies, are associated with recurrent fetal wastage, pregnancy complications, and thromboses. Aggressive medical treatment using aspirin and steroids has been recommended. Fifty-one patients with antiphospholipid antibodies, only four with underlying connective tissue disorders, were followed through 53 pregnancies. Aggressive therapy was used in 33 pregnancies, 90.9% of which resulted in successful obstetric outcomes, a highly statistically significant difference compared with previous pregnancies in the same patients. Most pregnancies among nine patients receiving single-agent therapy (aspirin or steroids alone) and eight patients not treated also had successful outcomes. A 48.6% complication rate was found in association with therapy, particularly gestational diabetes mellitus. There was no statistical correlation between dose or duration of therapy and development of treatment-related complications. Although a subgroup of patients with antiphospholipid antibodies will benefit from aggressive therapy, the high complication rate warrants close observation.