Catastrophic antiphospholipid syndrome during pregnancy and puerperium: maternal and fetal characteristics of 15 cases

BACKGROUND: The catastrophic variant of the antiphospholipid syndrome (APS) is a life-threatening form of presentation of this syndrome that can be triggered by several factors. AIM: To describe the characteristics of patients who developed catastrophic APS triggered during pregnancy and puerperium. METHODS: A review of the first 255 cases collected in the website-based "CAPS Registry" was undertaken. Three new and unpublished cases of catastrophic APS developed during pregnancy and puerperium were added. RESULTS: Fifteen cases were identified. The mean (range) age was 27 (17-38) years. Most patients had a previous unsuccessful obstetric history. In 7 of 14 (50%) cases with available medical history, the catastrophic APS appeared during pregnancy, in 6 (43%) during the puerperium and in 1 (7%) after curettage for a fetal death. The main clinical and serological characteristics were similar to those patients with catastrophic APS triggered by other factors, except for a history of a higher prevalence of previous abortions (p<0.01). Several specific features were found, including the HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome in 8 (53%) patients, placental infarctions in 4 (27%) patients, and pelvic vein thrombosis and myometrium thrombotic microangiopathy in 1 (7%) patient each. Mortality rate was high for the mothers (46%), and for the babies (54%). CONCLUSIONS: It is important to consider the possibility of the development of catastrophic APS in those patients with signs of HELLP syndrome and multiorgan failure during pregnancy or puerperium, especially in those patients with previous history of abortions and/or thrombosis.     

Thrombotic microangiopathy with liver, gut, and bone infarction (catastrophic antiphospholipid syndrome) associated with HELLP syndrome

Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome is a thrombotic microangiopathy complicating pregnancy and shares many clinical and biological features with thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Thrombotic microangiopathy is also a pathological feature of catastrophic antiphospholipid syndrome (CAPS). An association between refractory HELLP syndrome and antiphospholipid syndrome (APS) has been reported in a few cases. We describe a 19-year-old woman with APS and multiorgan failure conforming to a diagnosis of CAPS who developed refractory HELLP syndrome.     

Recurrent thrombosis prevention with intravenous immunoglobulin and hydroxychloroquine during pregnancy in a patient with history of catastrophic antiphospholipid syndrome and pregnancy loss

We report a case of a 36-year old patient with prior history of thrombosis in a setting of antiphospholipid antibody syndrome (APS) as well as pregnancy-associated catastrophic antiphospholipid syndrome (CAPS), resulting in multi-organ infarction and pregnancy loss. The episode of CAPS occurred while she was receiving antepartum low-dose aspirin and therapeutic-dose enoxaparin. This patient presented again at 6 weeks gestation and ultrasounds were consistent with fetal growth restriction, concerning for placental insufficiency and thrombosis. This time, hydroxychloroquine and monthly intravenous immunoglobulin (IVIG) infusions were added to her prophylaxis regimen, resulting in a successful delivery. Platelet count and antiphospholipid antibody titers were routinely monitored throughout pregnancy as markers of disease activity for APS. Current thromboprophylaxis guidelines do not address therapeutic options to prevent further pregnancy morbidity in women who develop recurrent episodes of thrombosis or CAPS despite receiving adequate anti-thrombotic treatment. Use of hydroxychloroquine and IVIG has been associated with good outcomes in this subset of patients.     

The HELLP syndrome in the antiphospholipid syndrome: retrospective study of 16 cases in 15 women

OBJECTIVE: To study the characteristics of the haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome in the antiphospholipid syndrome (APS) and its influence on the subsequent pregnancies. METHODS: This was a retrospective analysis of 16 episodes of HELLP complicating APS in 15 women. RESULTS: HELLP was complete in 10 cases and partial in six. It occurred during the second trimester in seven cases (the earliest at 18 weeks' gestation), the third trimester in seven cases, and the day following delivery in two cases. Pre-eclampsia was present in six cases and eclampsia in five. Outcome of pregnancies was: live birth (n = 8), stillbirth (n = 2) and fetal death (n = 6). APS was primary in nine women and secondary to systemic lupus erythematosus (SLE) in six. HELLP revealed primary APS in six cases. Seven women were not treated. Low dose aspirin was empirically prescribed in one woman whose APS had been undiagnosed despite a history of two fetal deaths. In the other women, therapy consisted of aspirin (n = 8), low molecular weight heparin with a dose varying between 3000 and 12 000 U daily (n = 5), and high dose immunoglobulin every 4 weeks (n = 2), hydroxychloroquine (n = 4), and prednisone (n = 6). Six women had seven subsequent pregnancies, 3-6 years after the complicated pregnancy. HELLP recurred at 33 weeks' gestation in one woman with SLE treated with prednisone, hydroxychloroquine, aspirin, and enoxaparin, and pregnancy ended in live birth. One woman became pregnant after in vitro fertilisation and embryo transfer, but pregnancy ended in fetal death despite prednisone, hydroxychloroquine, and enoxaparin. Four women had five uneventful pregnancies with 100 mg daily aspirin and heparin. CONCLUSIONS: APS may be revealed by HELLP. In APS, HELLP is associated with pre-eclampsia/eclampsia in most cases and seems to occur earlier than in the general population. Heparin plus aspirin may prevent obstetric complications in the subsequent pregnancies.     

Pregnancy outcome in patients with antiphospholipid syndrome after cerebral ischaemic events: an observational study

Among the most prominent features associated with antiphospholipid syndrome (APS) are cerebral ischaemic events (CVE). Pregnancy with APS increases the risk of thrombosis, including CVE. This study was undertaken to assess the risk of obstetric complications and recurrence of CVE during pregnancy in women with APS and previous CVE. We prospectively observed 23 pregnancies in 20 women (median age 31 years) with primary (n?=?8) or secondary APS (n?=?12). Eight patients had transient ischaemic attacks (TIA) and 12 had stroke before pregnancy. All patients received aspirin 100?mg daily in combination with low molecular weight heparin (LMWH) during their pregnancies. The live birth rate was 91.3% (n?=?21). Obstetrical complications consisted mainly of preeclampsia (n?=?8, 34.8%) and preterm delivery (n?=?9, 42.9%). The risk for preeclampsia increased in patients who were positive for multiple antiphospholipid antibodies (aPL) (odds ratio (OR) 3.06 (95% confidence interval (CI) 1.01-9.32)) per positive aPL test (i.e anticardiolipin antibody, anti-?2-glycoprotein I antibody, lupus anticoagulant) (p 0.049). Three patients experienced recurrent CVE in the context of pregnancy (one during pregnancy, two in the postpartum period). We found an increased, but not significant, risk of a new episode of cerebral ischaemia in patients with pregnancies complicated by preeclampsia (two out of the eight preeclampsia (p 0.15). Despite treatment, there is a significant risk for pregnancy complications in APS patients with previous CVE. Especially in the context of preeclampsia, anticoagulation should be given rigorously to prevent recurrence of CVE.     

Lupus and the antiphospholipid syndrome in pregnancy and obstetrics: clinical characteristics, diagnosis, pathogenesis, and treatment

The antiphospholipid syndrome (APS) in pregnancy is associated with repeated miscarriages and fetal loss. Other complications of pregnancy such as preeclampsia and placental insufficiency are also frequently reported during pregnancy in APS. The pathogenesis of pregnancy failures in APS is related to both the thrombophilic effect of antiphospholipid antibodies and also to different mechanisms including a direct effect of antibodies on trophoblast differentiation and invasion. Although optimal pharmacologic treatment is essential to achieve a successful outcome in APS pregnancy, the standard APS pharmacologic treatment alone may not be sufficient. A good obstetric outcome is the result of careful obstetric monitoring, proper delivery timing, and skillful neonatal care. A multidisciplinary team (obstetricians, rheumatologists, and neonatologists) and the progress in neonatal intensive care are as important as drugs in achieving a good obstetric outcome and to reduce the possible consequences of premature delivery.     

Diagnosis of antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent vascular thrombosis and pregnancy losses. Laboratory diagnosis of APS relies on the demonstration of a positive anticardiolipin antibody test by an in-house or commercially available enzyme-linked immunosorbent assay, or on the presence of lupus anticoagulant by a coagulation-based test. Persistence of the positive results must be demonstrated, and other causes and underlying factors considered. Although it is universally recognized that the routine screening tests (anticardiolipin antibody or lupus anticoagulant) might miss some cases of APS, careful differential diagnosis and repeat testing are mandatory before the diagnosis of 'seronegative APS' can be made. Correct identification of patients with APS is important because prophylactic anticoagulant therapy can prevent thrombosis from recurring and treatment of affected women during pregnancy can improve fetal and maternal outcome.     

Antiphospholipid-Syndrom 2007

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent vascular thrombosis and loss of pregnancy in association with the presence of antiphospholipid antibodies (APA) detectable as lupus anticoagulants, anticardiolipin antibodies or anti-β2 glycoprotein I antibodies. The pathophysiological importance of APA in APS is accepted, however, the mechanisms leading to thrombosis are likely to be multifactorial and are so far unclear. Without a prior thrombosis, the risk of developing a new thrombosis in healthy patients with APA is slightly increased (<1% per year). However, the risk of a recurrent thrombosis increases considerably (>10% per year) in patients with a history of thrombosis without anticoagulation. The careful and correct identification of patients with APS is important because prophylactic anticoagulation can reduce the risk of recurrent thrombotic events, and during pregnancy can improve fetal and maternal outcome.     

Management of Obstetric Antiphospholipid Syndrome

Recurrent early miscarriages (excluding chromosomal anomalies), late fetal loss, and maternal thrombosis are characteristic of obstetric antiphospholipid syndrome (APS). Obstetric complications such as preeclampsia, fetal growth restriction, premature delivery, and fetal death also occur in higher frequency in APS patients than in the general population. A high-risk obstetric center is needed for proper evaluation of and intervention with pregnant women with APS. Association with lupus carries additional risk of thrombosis when antiphospholipid antibodies (aPLs) are present. Gestational results with live births are improved to about 80% when antithrombotic therapy is used, but failure in 20% to 30% of the cases despite correct treatment with low-dose aspirin with or without heparin reveals new pathways for pregnancy loss in APS and unmet needs. At the moment, there is no recommendation to investigate patients with infertility for the presence of aPLs.     

The relation between antiphospholipid syndrome-related pregnancy morbidity and non-gravid vascular thrombosis: A review of the literature and management strategies

The antiphospholipid syndrome (APS) is associated with pregnancy morbidity and vascular thrombosis in the presence of circulating antiphospholipid (aPL) antibodies. Clinical manifestations of aPL antibodies represent a spectrum (asymptomatic, pregnancy events, vascular events, or both pregnancy and vascular events), and APS should not be considered a single disease with a predictable outcome. Patients with aPL antibodies are at increased risk of vascular thrombotic events during pregnancy, the postpartum period, and even during long-term follow-up after an APS-related pregnancy event. Therefore, the purpose of this paper is to review the relation between APS-related pregnancy morbidity and vascular thrombosis, and to address the importance of prophylactic therapy during and after APS pregnancies to prevent maternal thrombotic complications. During pregnancy, low-dose aspirin (LDA) should be considered for all patients with aPL antibodies and heparin should be added to LDA in patients fulfilling the Sapporo criteria for definite APS. During delivery, especially with caesarian section, periods without anticoagulation should be kept to an absolute minimum. Some data suggest that LDA might be effective against future non-gravid vascular thrombosis in patients with APS and a history of only pregnancy morbidity.     

Thrombotic events during long-term follow-up of obstetric antiphospholipid syndrome patients

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and/or venous thromboses and/or pregnancy-associated morbidity. Some patients develop only obstetric complications (obstetric APS), but data on the frequency of thrombotic events during the follow-up of these patients are scarce. This study was undertaken to evaluate the rate of thrombotic events after obstetric APS diagnosis according to the 2006 revised criteria. In total, 32 obstetric APS patients were retrospectively studied, with mean follow-up of 50?±?37 months. After delivery, aspirin was prescribed to all patients as primary thrombosis prevention. The thrombosis rate was 3.3/100 patient-years and was 4.6, 4.5 and 10/100 patient-years when we considered at least two antiphospholipid antibody positivities (among lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein-I), antinuclear antibody positivity or systemic lupus erythematosus-associated APS patients, respectively. The thrombosis rate was high after obstetric APS diagnosis, even for patients taking aspirin. Larger, prospective studies are needed to confirm this high frequency and determine the associated risk factors.     

Thrombophilias and vascular placental pathology. A survey of the literature

PURPOSE: Hereditary thrombophilia as antiphospholipid syndrome (APS) may represent a new risk factor for placental vascular diseases. CURRENT KNOWLEDGE AND KEY POINTS: General screening for biological abnormalities related to thrombophilia is poorly associated with placental vascular diseases and therefore, may be unwarranted. Women with an history of thrombotic diseases may be at risk for late fetal loss or preeclampsia. Adverse obstetric outcomes are particularly high despite anticoagulation regimens in patients with APS. A high frequency for biological abnormalities related to thrombophilia was detected in pregnancies complicated by late fetal loss in comparison with controls. However, no beneficial strategy prevention was clearly reported and therefore, a selective testing was actually debated for these patients. FUTURE PROSPECTS AND PROJECTS: Searching for acceptable treatment alternatives in patients with APS in order to reduce the high rate for pregnancy complications which may be persistent despite anticoagulation regimens. To determine by controlled studies the role for a prophylactic low molecular weight heparin regimens in patients with haemostatic abnormalities and previous pregnancy complications.     

Implementation of multidisciplinary care reduces maternal mortality in women with sickle cell disease living in low‐resource setting

Sickle cell disease (SCD) is associated with adverse pregnancy outcome. In women with SCD living in low‐resource settings, pregnancy is associated with significantly increased maternal and perinatal mortality rates. We tested the hypothesis that implementing a multidisciplinary obstetric and hematology care team in a low‐resource setting would significantly reduce maternal and perinatal mortality rates. We conducted a before‐and‐after study, at the Korle‐Bu Teaching Hospital in Accra, Ghana, to evaluate the effect of a multidisciplinary obstetric‐hematology care team for women with SCD in a combined SCD‐Obstetric Clinic. The pre‐intervention period was assessed through a retrospective chart review to identify every death and the post‐intervention period was assessed prospectively. Interventions consisted of joint obstetrician and hematologist outpatient and acute inpatient reviews, close maternal and fetal surveillance, and simple protocols for management of acute chest syndrome and acute pain episodes. Primary outcomes included maternal and perinatal mortality rates before and after the study period. A total of 158 and 90 pregnant women with SCD were evaluated in the pre‐ and post‐ intervention periods, respectively. The maternal mortality rate decreased from 10 791 per 100 000 live births at pre‐intervention to 1176 per 100 000 at post‐intervention, representing a risk reduction of 89.1% (P = 0.007). Perinatal mortality decreased from 60.8 per 1000 total births at pre‐intervention to 23.0 per 1000 at post‐intervention, representing a risk reduction of 62.2% (P = 0.20). A multidisciplinary obstetric and hematology team approach can dramatically reduce maternal and perinatal mortality in a low‐resource setting.     

Thrombophilia and its Treatment in Pregnancy

Pulmonary embolism is the most common cause of maternal death during pregnancy and the puerperium in the industrialized world. The risk of venous thromboembolism (VTE) in pregnancy is 0.05%–1.8%, 6 times greater than in the non-pregnant state. The risk is increased in women over 35 years and those with obesity, previous VTE, operative delivery, or underlying thrombophilia. Women presenting with recurrent miscarriages, preeclampsia, intrauterine growth restriction, abruptio placentae, or stillbirth (all associated with microvascular thrombosis in placental blood vessels) have high incidence (65%) of thrombophilia. About 70% of the women who present with VTE during pregnancy are carriers of hereditary or acquired thrombophilia. Treatment of women with VTE during pregnancy, and especially those with thrombophilia, requires individualized dosing and duration of antithrombotic therapy and the formulation of thromboprophylactic strategies for future pregnancies. Warfarin is contraindicated during the first trimester due to fetotoxicity; unfractionated heparin (UFH) is associated with practical disadvantages and the risk of heparin-induced thrombocytopenia (HIT) and osteoporosis with long-term use. Low molecular weight heparins (LMWHs) are convenient to use, do not cross the placenta, carry a lower risk of HIT and osteoporosis, and are safe and effective. LMWHs are replacing UFH as the anticoagulant of choice during pregnancy and improve pregnancy outcome in women with a history of obstetric complications and confirmed thrombophilia.     

Antiphospholipid antibody syndrome

Opinion statement Antiphospholipid antibody syndrome (APS) is a recently defined autoimmune disorder characterized by recurrent vascular thromboses or recurrent pregnancy morbidity; these features are linked to the presence in blood of autoantibodies against negatively charged phospholipids or phospholipid-binding proteins. Thrombosis can occur in any tissue, in veins, arteries, or the microvasculature. Pregnancy morbidity in APS includes miscarriages or premature birth. Criteria that define the major clinical and laboratory features of APS were published in 1999. In patients with antiphospholipid antibodies and prior thrombosis or pregnancy morbidity, there is a high risk of recurrence that persists as long as antiphospholipid antibodies occur in blood. This risk for recurrence of thrombosis or pregnancy morbidity is greatly reduced by preventive anticoagulant therapy. Patients presenting with thrombosis in APS are initially managed in much the same way as are patients with vascular thrombosis owing to other causes. However, in patients with APS, high-intensity anticoagulation is usually needed to prevent recurrences of thrombosis. Thrombosis in APS is often multifactorial, as with non-APS thrombosis. Therefore, in all patients with APS, other reversible risk factors for thrombosis should be sought. The pregnancy outcome of women with APS who have had prior miscarriages is greatly improved by treatment during pregnancy with a combination of heparin and low-dose aspirin.     

Syndrome des antiphospholides « séronégatif », syndrome catastrophique,nouveaux anticoagulants : enseignements d’une observation de prise en charge difficile

Introduction

The diagnosis of the antiphospholipid syndrome (APS) is based on clinical and biological criteria including the persistent presence of antiphospholipid antibodies and thrombotic events or pregnancy morbidity. Heparins relayed by vitamin K antagonists (VKA) are the gold standard treatment for thrombosis.

Case report

We report a 17-year-old man who presented with an initially seronegative antiphospholipid syndrome, in whom the diagnosis was late, only obtained after anticoagulation withdrawing, when a catastrophic antiphospholipid syndrome (CAPS) with cutaneous lesions and disseminated intravascular coagulation syndrome occurred. For personal convenience, this patient was initially treated with fondaparinux followed by a new oral anticoagulant (rivaroxaban) before to return to the conventional VKA treatment.

Conclusion

The “seronegative” APS is a controversial concept reflecting the heterogeneity of antigenic targets for aPL. This diagnosis may be considered after a rigorous work-up, with the help of haemostasis laboratories testing new emerging aPL assays. In APS, the new anticoagulants represent an attractive option needing nevertheless prospective studies to evaluate their safety and efficacy. Lupus anticoagulant detection in patients treated by new oral anticoagulants is not easy by usually recommended coagulation tests.     

Control del embarazo en pacientes con lupus eritematoso sistémico/síndrome antifosfolípido. parte 2: seguimiento del embarazo

ObjectiveIn order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology set up a working group for the preparation of three consensus documents.MethodsEach of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology.ResultsThis second document contains the recommendations regarding the management of pregnancy in women with SLE and APS, including complications such as lupus activity, congenital heart block, thrombotic and obstetric manifestations of APS and placental vascular disease.ConclusionsThese multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.     

Transitory bone marrow oedema of the hip in pregnant patient with antiphospholipid syndrome: A case report

BackgroundTransient bone marrow oedema (BMO) of the hip presents with pain, is diagnosed by magnetic resonance imaging (MRI), and usually resolves within 6 months. Risk factors include pregnancy. Avascular necrosis of bone and an association with BMO are among the less common presentations of antiphospholipid syndrome (APS).Aim of the workTo present a young Croatian female APS patient who developed transient BMO during pregnancy which spontaneously resolved postpartum.Case reportAfter developing left leg deep vein thrombosis and positive lupus anticoagulant at 22 years old, the patient was diagnosed with primary APS. Antinuclear antibody was borderline, but classification criteria for SLE were not fulfilled. She had an early missed abortion during her first pregnancy while receiving low-weight molecular heparin (LWMH) (enoxaparin 40 mg), and her second pregnancy was to term with LWMH, aspirin, and hydroxychloroquine 200 mg daily. During the third trimester of this pregnancy, she developed excruciating bilateral hip pain to the point she could barely walk. Based on an MRI scan, the patient was diagnosed with bilateral BMO of the femoral head. The condition improved and resolved within four months with conservative treatment postpartum, as confirmed by followup MRI.ConclusionConsidering that pregnancy and APS are risk factors for BMO, both played a role in the development of BMO and the severity of presentation. This case report presents a differential diagnosis of hip pain in pregnant patients, especially with APS. Although APS is commonly associated with AVN, it may also be associated with transient BMO.     

Antiphospholipid syndrome 2007. Current aspects of laboratory diagnostics and their therapeutic consequences

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent vascular thrombosis and loss of pregnancy in association with the presence of antiphospholipid antibodies (APA) detectable as lupus anticoagulants, anticardiolipin antibodies or anti-beta2 glycoprotein I antibodies. The pathophysiological importance of APA in APS is accepted, however, the mechanisms leading to thrombosis are likely to be multifactorial and are so far unclear. Without a prior thrombosis, the risk of developing a new thrombosis in healthy patients with APA is slightly increased (<1% per year). However, the risk of a recurrent thrombosis increases considerably (>10% per year) in patients with a history of thrombosis without anticoagulation. The careful and correct identification of patients with APS is important because prophylactic anticoagulation can reduce the risk of recurrent thrombotic events, and during pregnancy can improve fetal and maternal outcome.