Influence of aspirin on the clinical outcomes of 103 anti-phospholipid antibodies-positive patients

One hundred and three consecutive asymptomatic anti-phospholipid (aPL) antibody-positive carriers, taking aspirin (n=75) or not (n=28), were studied retrospectively to determine whether aspirin could provide primary prevention of anti-phospholipid syndrome (APS) symptoms. All patients positive for anti-cardiolipin antibodies (aCL; >25 UGPL or UMPL) and/or lupus anti-coagulant were followed for a mean of 64+/-24.7 months.Among aPL-positive patients, 37 had systemic lupus erythematosus (SLE), 20 had prolonged activated partial thromboplastin times, 19 had other connective tissue diseases, 16 had autoimmune thrombocytopenia (AIT), 11 had diverse diseases. Nineteen patients experienced thrombotic event(s) during follow-up. Clinical features, biological parameters and hydroxychloroquine use were comparable for the two groups, but thrombotic events differed (log-rank test; P=0.02). Four of the 10 SLE patients not taking aspirin developed thrombosis compared with 3/27 SLE patients taking aspirin (log-rank test; P=0.03). Anti-phospholipid -positive patients with AIT developed fewer thromboses while taking aspirin (log-rank test; P=0.01). In conclusion, aPL-positive SLE and AIT patients should take aspirin to prevent APS manifestations. Prospective therapeutic trials are needed to confirm aspirin's prophylactic role in such patients.     

Foetal loss, liver necrosis and acute lupus erythematosus in a patient with antiphospholipid antibody syndrome.

The antiphospholipid antibody syndrome (APS) is characterized by arterial or venous thromboses and recurrent foetal loss. It occurs as primary disease, but also in the context of systemic lupus erythematosus (SLE). Whereas primary APS induces a thrombotic microangiopathy without significant inflammatory reaction, secondary APS in SLE is usually associated with vasculitis. Here we report a patient with APS who presented with acute diarrhoea and then developed a HELLP-like syndrome characterized by a spontaneous abortion, multifocal hepatic necroses and thrombocytopenia. Thereafter an acute flare of SLE with arthralgias, pleuritis, skin rash and glomerulitis occurred. Clinical amelioration was only achieved by combining curettage, anticoagulation and immunosuppression, a treatment taking into account the pathogenesis of HELLP-like disease, APS and SLE. To our knowledge this is the first reported case of APS associated with combined acute manifestations of these three syndromes triggered by a presumable intestinal infection.     

Budd-Chiari syndrome and severe thrombocytopenia in a patient with Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome

Systemic Lupus Erythematosus (SLE) is a rheumatic autoimmune disease characterized by multisystemic involvement with a variable prognosis. The association with Antiphospholipid Syndrome (APS) occurs in about 36% of the patients, raising additional problems with treatment and monitoring of these patients. The authors report a clinical case of a girl with SLE and APS who represented Budd-Chiari Syndrome and severe thrombocytopenia. The patient had severe thrombotic event and simultaneously a high hemorrhagic risk due to thrombocytopenia. Long-term resolution of the thrombocytopenia was achieved with mycophenolate mofetil. Long-term anticoagulation for thrombosis prophylaxis is required.     

Prophylactic antithrombotic therapy for patients with systemic lupus erythematosus with or without antiphospholipid antibodies: do the benefits outweigh the risks? A decision analysis

BACKGROUND: A high incidence of both arterial and venous thromboembolic events has been reported in patients with systemic lupus erythematosus (SLE), but the risks and benefits of primary prophylactic antithrombotic therapy have not been assessed. We measured the clinical benefit of 3 antithrombotic regimens in patients with SLE without antiphospholipid antibodies, with anticardiolipin antibodies, or with lupus anticoagulant. METHODS: A Markov decision analysis was used to evaluate prophylactic aspirin therapy, prophylactic oral anticoagulant therapy, and observation. Input data were obtained by literature review. Clinical practice was simulated in a hypothetical cohort of patients with SLE who had not experienced any previous episode of arterial or venous thromboembolic events. For each strategy, we measured numbers of thromboembolic events prevented and major bleeding episodes induced, and quality-adjusted survival years. RESULTS: Prophylactic aspirin therapy was the preferred strategy in all settings, the number of prevented thrombotic events exceeding that of induced bleeding episodes. In the baseline analysis (40-year-old patients with SLE), the gain in quality-adjusted survival years achieved by prophylactic aspirin compared with observation ranged from 3 months in patients without antiphospholipid antibodies to 11 months in patients with anticardiolipin antibodies or lupus anticoagulant. Prophylactic oral anticoagulant therapy provided better results than prophylactic aspirin only in patients with lupus anticoagulant and an estimated bleeding risk of 1% per year or less. CONCLUSIONS: Prophylactic aspirin should be given to all patients with SLE to prevent both arterial and venous thrombotic manifestations, especially in patients with antiphospholipid antibodies. In selected patients with lupus anticoagulant and a low bleeding risk, prophylactic oral anticoagulant therapy may provide a higher utility.     

Successful Delivery in a Pregnant Woman with Lupus Anticoagulant Positive Systemic Lupus Erythematosus Treated with Double Filtration Plasmapheresis

Abstract: The case was a 29 year old female who has suffered from systemic lupus erythematosus (SLE) since 15 years of age. The activity of SLE was low, and she took prednisolone orally. Her first pregnancy failed after 14 weeks. In the second pregnancy, she had thrombocytopenia, prolonged activated partial thromboplastin time (APTT), positive lupus anticoagulant (LAC) and thus was diagnosed with antiphospholipid antibody syndrome (APS). Combination therapy with steroids and aspirin was started, and she underwent treatment of double filtration plasmapheresis (DFPP) in the early stage of pregnancy. Her platelet count increased, and the value of APTT has normalized with DFPP treatment. She delivered successfully on the 32nd week of pregnancy. We think that DFPP is an effective and safe treatment in patients with an LAC positive pregnancy.     

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.     

Antiphospholipid (Hughes) syndrome in systemic lupus erythematosus

APS is found in 20% to 35% of patients with SLE. PAPS and secondary APS have similar features and aPL specificities. The clinical course of the secondary syndrome is independent of the activity and severity of lupus, but the presence of APS worsens the prognosis of patients with lupus. Some features of SLE may result from thrombosis in patients with APS; thus, these patients require anticoagulation rather than corticosteroids. Novel preliminary classification criteria for APS were formulated during a postconference workshop held in Sapporo, Japan, following the Eight International Symposium on Antiphospholipid Antibodies. Treatment of APS remains empirical because of limited controlled prospective data. There is strong evidence that patients with aPL-associated thrombosis are subject to recurrences and require prophylactic therapy. APS is a treatable cause of recurrent fetal loss in women with SLE. The treatment of choice is anticoagulation with heparin, either standard unfractionated heparin or LMWH. One of the main reasons for the improving outcomes in APS pregnancies is closer obstetric surveillance.     

Longitudinal study of antinuclear and anticardiolipin antibodies in pregnant women with systemic lupus erythematosus and antiphospholipid syndrome

The objective of this study was to perform a longitudinal follow-up of antinuclear antibodies (ANAs) and anticardiolipin antibodies titers (aCL) throughout pregnancy in a group of patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients during their therapy for the prevention of fetal loss and to examine their relationship with pregnancy outcome. Thirty patients and 15 controls were followed in the study. Fifteen patients had SLE (group I) and 15 had APS (group II, of which seven patients had primary APS and eight had APS secondary to SLE). All patients were receiving therapy for the prevention of fetal loss with prednisone and aspirin as part of an ongoing clinical trial in lupus pregnancy. If there was a history of previous thrombosis, heparin was added. Blood samples were taken at the 1st, 2nd, and 3rd trimesters (T) of pregnancy in order to assess the presence of IgG and IgM aCL antibodies (ELISA), anti-dsDNA ( C. luciliae) ANAs (HEp-2 cells), and immunospecific antibodies (antiextractable nuclear antigens). We collected 90 samples from patients and 45 samples from healthy controls. Group I (SLE) ANAs were positive in 100% during the 1st T, 67% in the 2nd T, and 67% in the 3rd T, with various immunofluorescence patterns. In five patients, aCL antibodies were detected without a history of APS (one in 1st T, three in 2nd T, and one in 3rd T). Fetal loss was observed in two patients, in one of whom it was associated with nephritis, high titers of ANAs, and anti-dsDNA. Another patient had pulmonary hemorrhage with anti-dsDNA and aCL. In group II, all but one patient with primary APS were negative to ANAs. In secondary APS, by contrast, 6/8 patients (75%) had positive ANAs at least during the 1st T. All seven patients with primary APS and 6/8 with secondary APS had aCL during pregnancy. In 9/15 (60%) patients from the APS group with a history of previous fetal loss, aCL became negative during pregnancy and they had live births. The disappearance of aCL was associated with improved fetal survival (relative risk, or RR, 0.67). ANAs in the control group were positive in 7% at low titers, and all of them were negative for aCL. Despite treatment, ANAs are prevalent during pregnancy in SLE patients and APS secondary to SLE. During pregnancy in SLE, aCL titers may appear. Decreasing titers and/or disappearance of aCL correlated with improved fetal prognosis in a subset of patients with APS.     

Antiphospholipid antibody-associated chorea

OBJECTIVE: To describe the clinical features, treatment, and outcomes of patients with antiphospholipid antibody (aPL)-associated chorea. METHODS: The study cohort consisted of consecutive patients with chorea evaluated between 1990 and 2005 with documented aPL at time of their neurologic diagnosis. RESULTS: Eighteen patients were identified, 4 with systemic lupus erythematosus (SLE). The 14 non-SLE patients experienced 1.6 vascular thromboses/pregnancy losses per person, while patients with SLE experienced 0.5 events/person. Four non-SLE patients (29%) and no SLE patients met criteria for antiphospholipid antibody syndrome (APS). None of these 4 tested positive for IgM anticardiolipin antibody (aCL). In contrast, 10 (71%) non-APS patients tested positive for IgM aCL. Chorea was most often bilateral, mild to moderate, and occurred once with a median age at onset of 44 and 33 years in non-SLE and SLE patients, respectively. Therapy included immunosuppression in 3 (21%) non-SLE patients and in all SLE patients. Antidopaminergic agents were used in 7 (39%). All patients responded to treatment. Five patients received anticoagulation for thrombosis and 2 died of bleeding complications, both non-SLE patients. CONCLUSION: aPL-associated chorea occurs most often in women and severity is mild to moderate. Clinical expression of chorea does not differ between those with and without SLE. Anticoagulation should be reserved for thrombosis treatment and not simply for chorea in the presence of aPL, as 2 patients died of bleeding. The absence of IgM aCL in patients with APS supports prior evidence that IgG aCL and lupus anticoagulant may be the more clinically relevant antibodies for thrombosis. However, IgM aCL may be important in patients with chorea.     

Hypocomplementemia in systemic lupus erythematosus and primary antiphospholipid syndrome: prevalence and clinical significance in 667 patients

The objective of the study was to analyse the prevalence and clinical significance of hypocomplementemia in a large series of patients diagnosed either with systemic lupus erythematosus (SLE) or with primary antiphospholipid syndrome (APS) and its association with the main clinical, hematological and immunological features of these diseases. Between 1992 and 2003, complement determinations (C3 and C4 levels, CH50 activity) were performed in 597 consecutive patients diagnosed with SLE (530 women and 67 men, mean age 32.6 years) and 70 with primary APS (57 women and 13 men, mean age 38.7) visited in our department. Complement determinations are routinely made at the first visit of patients and yearly during the follow-up. SLE and primary APS were diagnosed according to current classification criteria. Hypocomplementemia was detected in 371 (62%) of SLE patients. Compared with patients with normal complement values, those with hypocomplementemia showed a higher prevalence of female gender (P < 0.001), fever (P = 0.021), nephropathy (P < 0.001), cutaneous vasculitis (P = 0.023), positive anti-dsDNA antibodies (P = 0.012) and cryoglobulinemia (P < 0.001). In addition, patients with hypocomplementemia showed a higher prevalence of APS-related features such as hemolytic anemia (P = 0.001) and antiphospholipid antibodies (P < 0.001). Hypocomplementemia was prospectively related to accumulated hospitalization in SLE patients but not with the accumulated number of lupus flares or with the survival after follow-up of five years. In contrast, 33 (47%) patients with primary APS presented low complement values, which were associated with a higher prevalence of livedo reticularis (P = 0.022), thrombocytopenia (P = 0.004), lupus anticoagulant (P = 0.013), positive IgM-aCL (P = 0.039), positive ANA (P = 0.002) and anti-dsDNA (P = 0.046). The diagnostic value of hypocomplementemia in patients with SLE is based on the association with disease activity, immune-complex mediated manifestations (glomerulonephritis, cryoglobulinemia) and APS-related features (livedo reticularis, hemolytic anemia and aPL). Hypocomplementemia was found in nearly half of patients with primary APS, and was associated with some APS features (livedo reticularis, thrombocytopenia, aPL) but also with SLE-related immunological markers (ANA and anti-dsDNA), identifying a subset of patients with primary APS with a higher risk of evolving to SLE. These results clearly support the routine determination of complement factors in the clinical follow-up of patients with SLE and primary APS.     

An audit of pregnant women with prosthetic heart valves at a tertiary hospital in South Africa: a five-year experience

Background: Cardiac disease in pregnancy is a common problem in under-resourced countries and a significant cause of maternal morbidity and mortality. A large proportion of patients with cardiac disease have prosthetic mechanical heart valve replacements, warranting prophylactic anticoagulation. Aim: To evaluate obstetric outcomes in women with prosthetic heart valves in an under-resourced country. Methods: A retrospective chart review was performed of 61 pregnant patients with prosthetic valve prostheses referred to our tertiary hospital over a five-year period. Results: Sixty-one (6%) of 1 021 pregnant women with A diagnosis of cardiac disease had prosthetic heart valves. Fifty-nine had mechanical valves and were on prophylactic anticoagulation therapy, three had stopped their medication prior to pregnancy and two had bioprosthetic valves. There were forty-one (67%) live births, two (3%) early neonatal deaths, 12 (20%) miscarriages and six (10%) stillbirths. Maternal complications included mitral valve thrombosis (n = 4), atrial fibrillation (n = 8), infective endocarditis (n = 6), caesarean section wound haematomas (n = 7), broad ligament haematoma (n = 1) and warfarin embryopathy (n = 4). Haemorrhagic complications occurred in five patients and all five required blood transfusions. Conclusion: Prophylactic anticoagulation with warfarin in patients with mechanical heart valve prostheses was associated with high rates of maternal and neonatal complications, including significant foetal wastage in the first and early second trimesters of pregnancy. Health professionals providing care for pregnant women with prosthetic heart valves must consistently advise on family planning matters, adherence to anticoagulation regimes and consider the use of prophylactic anticoagulant regimens other than warfarin, particularly during the first trimester of pregnancy.     

Preclinical vascular disease in systemic lupus erythematosus and primary antiphospholipid syndrome

OBJECTIVE: To determine the prevalence of preclinical vascular disease and associated risk factors in patients with systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). METHODS: We consecutively studied 70 SLE patients and 25 primary APS patients without clinical coronary artery disease. The control group included 40 healthy women. Carotid ultrasound was performed and the intima-media wall thickness (IMT) and presence of plaque was investigated in all patients and controls. Traditional vascular risk factors and SLE-disease and treatment related factors were also analysed. RESULTS: SLE patients had a higher prevalence of traditional atherosclerosis risk factors: hypertension (P<0.005) and dyslipidaemia (P<0.05) and higher levels of total cholesterol (P = 0.03), triglycerides (P = 0.004) and apolipoprotein B (P = 0.04). The prevalence of carotid plaque was higher and appeared earlier in SLE patients than in the primary APS patients or controls (P<0.001). The IMT was similar in the three groups. SLE patients with secondary APS had a higher prevalence of carotid plaque than patients with primary APS (37.5% vs 8%, P = 0.03). The presence of plaque in SLE patients was associated with a higher SLICC score (2.40 +/- 1.78 vs 1.02 +/- 1.18, P = 0.002), higher ECLAM score (3.10 +/- 2.32 vs 1.84 +/- 1.59, P = 0.02) and older age (47.3 +/- 8.44 vs 37.38 +/- 11.28, P = 0.003) at the time of carotid ultrasound study. CONCLUSION: Plaque prevalence in patients with primary APS is similar to that of controls and inferior to that of SLE patients with secondary APS. SLE patients have a high prevalence of early carotid atherosclerosis that is associated with cumulative disease damage and disease activity.     

A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome

OBJECTIVE: Antiphospholipid antibodies (aPL) are major risk factors for thrombosis. Other clinical factors exist in antiphospholipid syndrome (APS) patients which may have an additive or preventive effect on thrombosis. We therefore performed a cross-sectional study to analyse additive clinical thrombotic risk factors and possible preventive treatments in APS patients, and to compare the results with those obtained in asymptomatic aPL-positive (no history of vascular thrombosis or pregnancy morbidity) patients. METHODS: We identified 77 APS patients with non-gravid thrombotic events (group A) and 56 asymptomatic aPL-positive patients (group B). The study periods were defined as 6 months prior to the time of first vascular event in group A and 6 months prior to the patient's last visit in group B. Medical records were reviewed to evaluate the incidence of hypertension, diabetes mellitus, hypercholesterolaemia, regular cigarette smoking, oral contraceptive use or hormone replacement therapy, surgical procedures, pregnancy with or without an APS-related event, malignancy and infections. In addition, any history of thrombocytopenia or the use of aspirin, hydroxychloroquine, corticosteroids or immunosuppressives during the study periods was recorded. Bivariate statistical analysis and logistic regression tests were performed to compare groups. RESULTS: In group A, 75% (n=58) of patients and in group B 48% (n=27) of patients had at least one of the additional risk factors during the study periods. In the bivariate analysis, pregnancy (P=0.005) and surgical procedures (P=0.04) were significantly more frequent in group A, while aspirin (P<0.001), hydroxychloroquine (P<0.001) and corticosteroids (P=0.002) were used significantly more frequently in group B. In logistic regression, the probability of an event was decreased by taking aspirin and/or hydroxychloroquine. In women only, the probability of an event was increased with thrombocytopenia and pregnancy or surgical procedures. The incidences of hypertension and smoking and the presence of more than one risk factor were significantly associated with arterial thrombosis but not venous thrombosis. CONCLUSION: While traditional risk factors were similar between groups, pregnancy and surgical procedures increased the risk of thrombosis. Hypertension and smoking were associated with arterial events. Possessing a combination of risk factors may increase the occurrence of arterial thrombosis but not venous thrombosis. Use of aspirin and/or hydroxychloroquine may be protective against thrombosis in asymptomatic aPL-positive individuals.     

The antiphospholipid syndrome as a disorder initiated by inflammation: implications for the therapy of pregnant patients

Arterial thrombosis, venous thrombosis and morbidity during pregnancy, or a combination of these events, are clinical outcomes associated with antiphospholipid antibodies produced by patients with antiphospholipid syndrome (APS). Our understanding of the etiology and pathogenesis of the syndrome is limited, but it has generally been considered a thrombophilic disease and treatment has focused on anticoagulation. Agents such as aspirin and heparin, administered alone or in combination, are empirical treatments that are used in the management of obstetric patients with APS. Clinical features, such as heart valve abnormalities, thrombocytopenia and livedo reticularis, suggest multiple pathogenic mechanisms and provide other therapeutic targets. Findings from research in animal models of APS challenge the dogma that this syndrome is a noninflammatory, thrombotic disease and provide evidence that activation of complement is crucial for complications in pregnancy. These studies, in addition to evidence of inflammatory-mediated tissue damage in placentae of patients with APS, suggest that therapy should also be directed towards preventing inflammation. This Review describes the potential mechanisms of tissue injury by antiphospholipid antibodies, the management of pregnant patients with APS and how heparin therapy might inhibit the pathogenic mediators of disease.     

Risk-based secondary prevention of obstetric antiphospholipid syndrome

Treatment of pregnant women with antiphospholipid syndrome (APS) should be set apart from that from thrombotic APS patients. Patients with a history of pregnancy morbidity but no vascular thrombosis are usually treated with a prophylactic dose of heparin plus low-dose aspirin; whereas, those with previous vascular thrombosis alone or associated with previous pregnancy morbidity, are commonly treated with a therapeutic dose of heparin generally combined with low-dose aspirin. However, in about 20% of pregnant APS women these regimens fail. In this context, we conducted a case-control study on a large multicentre cohort of conventionally treated pregnancies to verify whether specific laboratory profiles and/or clinical characteristics are predictive of unsuccessful pregnancy outcome during conventional treatments. Multivariate analysis showed that pregnancy failure during conventional therapies was independently associated with a history of both thrombosis and pregnancy morbidity, the presence of systemic lupus erythematosus (SLE) or other systemic autoimmune diseases and triple antiphospholipid antibody positivity. With the aim to discover the most effective and safe treatments in high-risk pregnant APS women a large-scale multicentre study focusing on the effect of treatments on pregnancy outcome in women with APS and further risk factors for pregnancy failure has been designed.     

Progression of antiphospholipid antibody syndrome to catastrophic antiphospholipid antibody syndrome acutely with cessation of antithrombotic therapy

Catastrophic antiphospholipid antibody syndrome (CAPS) is a serious condition that is often unrecognised with a high mortality. Cessation of anticoagulation in antiphospholipid antibody syndrome (APS) can have devastating consequences with progression to CAPS. Making a diagnosis of APS can however be challenging because of the evolving diagnostic criteria and difficulty in confirming thromboses. Management of these patients can also be complex, especially in those with coexistent thrombocytopenia. New potential treatments are emerging targeted on the immunomodulation of APS rather than just prevention of thrombosis. This article aims to highlight these diagnostic and management difficulties by reporting and discussing three cases of APS with progression to CAPS following cessation of anticoagulation, one with fatal consequences, with confirmation of CAPS on autopsy, and two with successful treatment and outcomes.     

Anti-beta2-glycoprotein I antibodies in pediatric systemic lupus erythematosus and antiphospholipid syndrome

OBJECTIVE: To determine whether serum beta2-glycoprotein I antibody (anti-beta2GPI) detection improves identification of pediatric subjects at risk for antiphospholipid syndrome (APS). METHODS: Serum antiphospholipid antibodies (aPL) were identified by anticardiolipin enzyme-linked immunosorbent assay (ELISA), lupus anticoagulant assays, and syphilis screening in children with primary APS, systemic lupus erythematosus (SLE), or SLE plus APS. Anti-beta2GPI level and isotype were determined by beta2GPI ELISA and correlated with clinical manifestations and other aPL assays. RESULTS: One hundred-ten subjects under 22 years of age and of mixed ethnicity were evaluated. Fifty-seven had SLE (including 14 with APS), 25 had primary APS, 16 had SLE-like APS, 6 were healthy children with aPL detected incidentally, 4 had other rheumatic diseases and 2 had other conditions. Anti-beta2GPI were detected in 48% of SLE subjects and did not improve aPL detection over standard tests. Anti-beta2GPI were associated with stroke (P = 0.014), but not with other APS manifestations, and were rarely detected in primary APS. Among subjects with APS manifesting as chronic thrombocytopenia, anti-beta(2)GPI distinguished subjects with SLE from those with primary APS. CONCLUSIONS: With the exception of stroke, anti-beta2GPI detection does not improve identification of pediatric APS over that of traditional aPL assays. Anti-beta2GPI are rare in pediatric primary APS, but may predict evolution of chronic thrombocytopenia to SLE.     

Efficacy of prophylactic warfarin for prevention of thalidomide-related deep venous thrombosis

BACKGROUND: Deep venous thrombosis (DVT) is a common complication of thalidomide treatment. There is little information to guide clinicians in selecting effective preventive treatments and physician practice varies. We sought to determine whether prophylactic anticoagulation with warfarin prevents DVT related to thalidomide treatment. METHODS: We reviewed the records of 131 patients receiving thalidomide for a variety of indications. Fifty-five patients were prescribed warfarin with the intent of preventing DVT. Thirty-seven patients received warfarin at a dose of 1-2 mg per day (low dose) and 18 received a dose intended to raise the INR to 2-3 (high dose). RESULTS: Twenty-one of the 131 patients developed venous thrombosis during thalidomide treatment. Eighteen of the 76 patients (23.7%) who were not prescribed prophylactic anticoagulation developed DVT compared to 3 of the 55 patients (5.5%) who were prescribed any dose of prophylactic warfarin (P = 0.010). Only 1 of the 37 patients who received low-dose warfarin developed DVT (P = 0.011). Bleeding complications occurred in 4 patients, all of whom were receiving high-dose warfarin. CONCLUSION: Prophylactic anticoagulation with warfarin reduces the risk of thrombosis during thalidomide treatment. Low-dose warfarin may be as effective as higher dose treatment and may result in fewer bleeding complications.     

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.     

Treatment of pregnant patients with antiphospholipid syndrome

Antiphospholipid Syndrome (APS) has been widely recognized as a risk factor for the recurrence of both thrombosis and pregnancy losses; however the optimal treatment of patients is debatable. The aim of this paper was to establish a consensus among experts on the treatment of APS in pregnancy. A questionnaire that described possible different clinical situations was sent to the International Advisory Board of the 10th International Congress on Antiphospholipid Antibodies. Sixteen experts from different medical branches and different geographic areas sent their replies. The consensus was that treatment for APS pregnant patients should be low molecular weight heparin (LMWH) and low dose aspirin (LDA). The dosage, and frequency of LMWH depends on different situations, including the body weight and past history. Patients with previous thromboses usually receive two injections per day. Warfarin can also be used from 14 to 34 weeks, for patients with previous stroke or severe arterial thromboses. The use of intravenous immunoglobulin (IVIG) seems to be restricted to patients with pregnancy losses despite conventional treatment. The experts usually advised barrier methods of contraception, intrauterine device (if the patient is not taking corticosteroids) or progestins. Oral contraception with oestrogens was usually avoided.