Primary Antiphospholipid Syndrome

Pregnancy morbidity is one of the clinical manifestations used for classification criteria of antiphospholipid syndrome (APS). During the 14th International Congress on Antiphospholipid Antibodies (aPL), a Task Force with internationally-known experts was created to carry out a critical appraisal of the literature available regarding the association of aPL with obstetric manifestations present in actual classification criteria (recurrent early miscarriage, fetal death, preeclampsia and placental insufficiency) and the quality of the evidence that treatment(s) provide benefit in terms of avoiding recurrent adverse obstetric outcomes. The association of infertility with aPL and the effectiveness of the treatment of patients with infertility and positive aPL was also investigated. This report presents current knowledge and limitations of published studies regarding pregnancy morbidity, infertility and aPL, identifying areas that need better investigative efforts and proposing how critical flaws could be avoided in future studies, as suggested by participants of the Task Force. Except for fetal death, there are limitations in the quality of the data supporting the association of aPL with obstetric complications included in the current APS classification criteria. Recommended treatments for all pregnancy morbidity associated to APS also lack well-designed studies to confirm its efficacy. APL does not seem to be associated with infertility and treatment does not improve the outcomes in infertile patients with aPL. In another section of the Task Force, Dr. Jane Salmon reviewed complement-mediated inflammation in reproductive failure in APS, considering new therapeutic targets to obstetric APS (Ob APS).

Autoantibodies neutralizing human ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motif), the metalloprotease that physiologically cleaves von Willebrand factor, are a major cause of severe deficiency of the protease and of acquired thrombotic ...

Despite the strong association between antiphospholipid antibodies (aPL) and thrombosis, the pathogenic role of aPL in the development of thrombosis has not been fully elucidated. Proposed pathophysiological mechanisms may be categorized into two types. First, aPL may act in vivo by disrupting the kinetics of the normal procoagulant and anticoagulant reactions occurring on cell membranes. Second, aPL may stimulate certain cells thereby altering the expression and secretion of various molecules. In this article, we review the mechanisms by which aPL may develop thrombotic events. ᮊ

Livedo reticularis (LR) is a skin vasculopathy that has been frequently described in patients with anti-phospholipid syndrome (APS) and reported to be present in association with valvular heart pathology and strokes (i.e. Sneddon's syndrome).

A 48-year-old white woman was using propylthiouracil (PTU) 100 mg daily since April 2000 for hyperthyroidism treatment. In October 2003, she was admitted with fever, abdominal pain, diarrhea, polyarthritis, and progressive weight loss. The liver and spleen were mildly enlarged. Neurologic, musculoskeletal, ophthalmologic, and gynecologic examinations were normal. An abdominal computed tomography scan showed thickness of distal ileum, cecum, and right colon. Several intestinal ulcers were found on colonoscopy ( . Features of a microscopic vasculitis were detected on biopsy of ulcers ( . A perinuclear anti-neutrophilic cytoplasmic antibody (P-ANCA) test was positive with high levels of antimyeloperoxidase antibody. Laboratory and clinical characteristics of antiphospholipid syndrome were also found. She was diagnosed as having PTU-induced vasculitis. In addition to stopping the drug, a pulse therapy with 250 mg of methylprednisolone twice a day for 3 days was introduced. A dramatic improvement occurred. She underwent radioiodine therapy for hyperthyroidism, and azathioprine 2 mg · kg Ϫ1 · day Ϫ1 was prescribed. A follow-up colonoscopy after seven months of therapy revealed complete healing of mucosal ulcers, and she was free of symptoms.

A 31-year-old woman was admitted to the hospital for investigation of left lower limb thrombophlebitis. History, physical examination, and laboratory investigations led to the diagnosis of systemic lupus erythematosus (SLE), complicated by secondary antiphospholipid syndrome (APS). Treatment included steroids, azathioprine, aspirin, and low molecular weight heparin. Sixty-three days later, she was admitted to the hospital again because of high fever, macroscopic hematuria, and dyspnea. Laboratory testing showed anemia and impaired renal function. High-resolution chest computed tomography (CT) revealed bilateral multiple peribronchial infiltrates with hemorrhage. Magnetic resonance imaging (MRI) angiography of the kidneys revealed left renal vein thrombosis combined with ischemia of the left kidney. Cyclophosphamide and methylprednisolone pulse treatment as well as intravenous immunoglobulins were started immediately. Despite intensive immunosuppressive and supportive treatment, she suffered three relapses of alveolar hemorrhage and died on day 40, due to severe intracerebral bleeding. The final diagnosis was catastrophic APS with diffuse alveolar hemorrhage and kidney involvement. The unusual combination of recurrent alveolar hemorrhage and death from intracerebral hemorrhage rather than thrombosis in a CAPS patient is discussed.

PURPOSE: To determine the prevalence of antiphospholipid antibodies and other immunologic abnormalities in patients with occlusive retinal vascular events, exempt from conventional risk factors of retinal thrombosis. • METHODS: Forty patients with retinal vascular occlusion (26 with retinal vein occlusions, eight with arterial occlusions, two with combined venous and arterial occlusions, and four with venous occlusions plus vasculitis), free of main accepted risk factors for retinal thrombosis, were prospectively screened for antiphospholipid antibodies (anticardiolipin-antibodies and lupus anticoagulant) and other immunologic abnormalities. Fourteen patients were younger than 50 years. Prevalence and mean values of antiphospholipid antibodies (aPL) were compared with those in a homogeneous control group of 40 patients. • RESULTS: The prevalence of antiphospholipid antibodies in the study group was 22.5% (nine of 40). Comparison with control group prevalence (5% [two of 40]) showed a statistically significant difference (P ‫؍‬ .04). Six patients in the study group disclosed positivity for IgG-anticardiolipin antibodies, one patient for IgM anticardiolipin antibodies, and two patients for both isotypes IgG and IgM anticardiolipin antibodies. The antibody assay for lupus anticoagulant was negative for all patients. Three patients were diagnosed as having primary antiphospholipid antibody syndrome and are undergoing systemic anticoagulant therapy. Relevant immunologic abnormalities were also found (27.5% with antinuclear antibodies, 35% with elevation of circulating immune complexes, 35% with complement deficiency, 30% with positive rheumatoid factor, and 17.5% with positive C-reactive protein). Thirteen patients (32.5%) had more than four parameters altered. No significant association was found between prevalence or mean values of anticardiolipin antibody and patients younger than 50 years. • CONCLUSIONS: The high prevalence of anticardiolipin antibodies in patients with vaso-occlusive retinopathy exempt from conventional risk factors, and the relevant diagnostic and therapeutic implications, lead us to recommend a systematic search for specific antiphospholipid antibodies in such patients. (Am J Ophthalmol 1999; 128:725-732. © 1999 by Elsevier Science Inc. All rights reserved.)

Purpose. – The association of antiphosphatidylethanolamine antibodies (aPE) as the only antiphospholipid antibody with antiphospholipid syndrome (APS) is discussed. The aPE was described as the sole antibody in many cases suggesting APS. aPE was not included in the Sapporo criteria for the classification of APS.Methods. – We investigated the clinical features of 20 patients with aPE only; 17 patients had symptoms potentially

Purpose The objective of the present study was to evaluate fetal biometry, Doppler values, and perinatal outcomes in pregnant women with antiphospholipid syndrome treated with acetylsalicylic acid and heparin. Study design Twenty-five pregnant women with antiphospholipid syndrome using 100 mg/day acetylsalicylic acid and 5,000 IU heparin every 12 h were evaluated in this prospective observational study. Ultrasonography was performed between 24 and 38 weeks of gestational age to assess estimated fetal weight, placental thickness, amniotic fluid index, fetal biophysical profile and Doppler evaluation of maternal uterine arteries, and fetal middle cerebral and umbilical arteries. Data regarding Apgar score, gender, delivery mode, and birth weight and length were recorded after birth. Results The observed values for ultrasonographic assessment and perinatal outcomes were not very different from the expected values for normal pregnancies. The birth weight was 2863.3 ± 737.7 g (mean ± SD) and length was 46.8 ± 4.2 cm. Only one newborn (4%) had the 1-min Apgar score\7 and all had the 5-min Apgar score[7. Conclusion Gestational and perinatal evaluation of pregnant women with antiphospholipid syndrome using both acetylsalicylic acid and heparin was reassuring.

Objective: Neuropsychiatric symptoms may be the main manifestations and very early symptoms of developing autoimmune diseases. Early detection and treatment could reverse psychotic symptoms and restore cognitive function. Case Report: A 24-year-old woman presented with acute psychotic symptoms. Routine physical examinations revealed only mild fever. Due to positive antiphospholipid antibodies, low protein S with elevated D-dimer and brain hypoperfusion, early-phase antiphospholipid syndrome (APS) was suspected. Early immunomodulation treatment led to complete remission of the psychotic symptoms, preservation of cognitive function and prevention of APS progression. Conclusion: Since early detection and treatment can reverse the progression of autoimmune diseases with central nervous system involvement, these should be highlighted when managing high-risk patients.

The antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by recurrent thrombosis and/or obstetrical morbidity in the presence of persistently positive antiphospholipid antibodies. Recent insights into the pathogenesis of APS have begun to elucidate pathophysiology and led to the identification of potential therapeutic interventions. The objective of this review is to examine the advances in this field and highlight the areas of further investigation. Several mechanisms of thrombosis and pregnancy loss in APS have been proposed. These include activation of endothelial cells, monocytes, and platelets, and/or inhibition of natural anticoagulant and fibrinolytic systems by antiphospholipid antibodies. However, in many cases the underlying molecular mechanisms and their relevance to the human disorder remain uncertain. New therapeutic agents such as statins, hydroxychloroquine, rituximab, complement inhibitors, and interventions aimed at disruption of intracell...

Objective: Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course and prognosis. We sought to develop evidence-based recommendations addressing the major issues in the management of SLE. Methods: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Key questions for the management of SLE were compiled using the Delphi technique. A systematic search of PubMed and Cochrane Library Reports was performed using McMaster/Hedges clinical queries' strategies for questions related to the diagnosis, prognosis, monitoring and treatment of SLE. For neuropsychiatric, pregnancy and antiphospholipid syndrome questions, the search was conducted using an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence, and agreement on the statements was measured across the 19 specialists. Results: Twelve questions were generated regarding the prognosis, diagnosis, monitoring and treatment of SLE, including neuropsychiatric SLE, pregnancy, the antiphospholipid syndrome and lupus nephritis. The evidence to support each proposition was evaluated and scored. After discussion and votes, the final recommendations were presented using brief statements. The average agreement among experts was 8.8 out of 10. Conclusion: Recommendations for the management of SLE were developed using an evidence-based approach followed by expert consensus with high level of agreement among the experts.

Autoimmune disorders are rare human diseases characterized by the presence of circulating autoantibodies that bind the body's own structural compounds as target antigens. The detection of autoantibodies is important for the diagnostic process. Immunofluorescence and immunoassay methods do not allow a reliable characterization of binding characteristics. Therefore, novel analytical techniques should be considered. This review describes the application of surface plasmon resonance biosensor systems for the diagnosis of autoimmune disorders. The covalent attachment of native antigens to the sensor chip is a suitable method for obtaining highly reproducible analyses of autoantibodies, allowing the evaluation of kinetic rate and affinity constants, and it may enable the identification of disease-relevant autoantibodies linked to disease progression. The autoantibody microarray is another future-oriented technique. Patterns of differential antigen recognition should allow early diagnosis. This is due to the fact that a broad range of autoreactive B cell responses in autoimmune disorders can only be mirrored by including a sufficient number of antigens in a microarray format.

There are few conditions in medicine associated with more heartache to patients than recurrent pregnancy loss (RPL). The management of early RPL is a formidable clinical challenge for physicians. Great strides have been made in characterizing the incidence and diversity of this heterogeneous disorder, and a definite cause of pregnancy loss can be established in more than half of couples after a thorough evaluation. In this review, current data are evaluated and a clear roadmap is provided for the evaluation and treatment of RPL.

Although many may think of rheumatology as the study of arthritis, occurring predominantly in older patients, many autoimmune and connective tissue diseases are actually diseases of young and middle-aged women. This article reviews common rheumatic diseases that most frequently occur in women, including fibromyalgia, rheumatoid arthritis (RA), Sjogren's syndrome, systemic lupus erythematosus (SLE), and the antiphospholipid antibody syndrome (APLS). In this group of patients, many women are of childbearing potential, and special considerations for pregnancy can and often do arise; these are discussed as well. In addition, rheumatic conditions that more frequently affect older women, such as osteoarthritis (OA), polymyalgia rheumatica (PMR), and temporal arthritis, are discussed. Osteoporosis, which has been recognized as a significant women's health issue, is reviewed.

Physicians periodically encounter patients with an extraordinarily accelerated course of hypercoagulability who develop thromboses in multiple organ systems over days to weeks. Such patients may harbor underlying hypercoagulable clinical conditions, but their clinical course sets them apart from most patients with similar risk factors. Underlying triggers of "thrombotic storm" include pregnancy, inflammation, trauma, surgery, and infection. Aggressive anticoagulant therapy may control thrombotic storm, yet thrombotic storm may resume with even brief interruptions of anticoagulant therapy. The authors of this communication formed the Thrombotic Storm Study Group in order to identify clinical characteristics of such patients, thus constructing preliminary criteria to better define, identify, and study the course of patients deemed to have thrombotic storm. The characteristics culled from these 10 patients are: younger age (oldest was 38 years old at time of presentation); at least 2 arterial or venous (or both) thromboembolic events, typically in unusual sites with or without microangiopathy; unexplained recurrence; and frequently proceeded by a trigger. The following characteristics were not used in defining thrombotic storm: underlying malignancies; use of acute myocardial infarction as a defining arterial event in the setting of established coronary artery disease; use of cocaine; thrombotic complications expected with various intravascular devices; known paroxysmal nocturnal hemoglobinuria or myeloproliferative disorders; severe trauma; and premorbid conditions.

The antiphospholipid syndrome (APS) is an acquired thombophilia, which is characterized by one or more thrombotic episodes and obstetric complications in the presence of antiphospholipid (aPL) antibodies (Abs). aPL Abs are detected by laboratory tests such as lupus anticoagulant (LA), anticardiolipin (aCL) and anti-2 -glycoprotein I ( 2 GPI) Abs. This article reviews the most current pathophysiological aspects of APS with emphasis in thrombotic and proinflammatory mechanisms mediated by aPL antibodies.

Multidisciplinary approach and patient counselling have been the key points in the improvement of the management of pregnancy in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Most of these women can have successful pregnancy when thoroughly informed and instructed on several different issues. Disease activity should be in stable remission prior to pregnancy in order to reduce the chance for flare during pregnancy. To this purpose, medications must be modulated: "safe" drugs should be continued throughout pregnancy, embryotoxic/foetotoxic drugs should be withdrawn timely, and beneficial drugs such as low dose aspirin and heparin should be added for prophylaxis of maternal and foetal outcome, especially in the presence of antiphospholipid antibodies. The safety profile of anti-rheumatic drugs during pregnancy and breastfeeding should be kept constantly updated, as new data from inadvertent exposure accumulates and new drugs (especially biological agents) are available. Patients may carry autoantibodies that can negatively affect the baby, being neonatal lupus the prototypical case of passively acquired autoimmunity. Research has been greatly active in this field and more information on risk stratification and management are now available for counselling. The effect of both autoantibodies and drug exposure has been evaluated in the offspring: some concerns about learning disabilities have been raised, but these are treatable conditions that are likely to be overcome.

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.

In patients with primary APS, expression of tissue factor (TF) on the surface of monocytes is increased, which may contribute to thrombosis in these patients. However, the intracellular mechanisms involved in aPL-mediated upregulation of TF on monocytic cells are not understood. This study was undertaken to investigate the intracellular signals induced by aPL that mediate TF activation in monocytes from APS patients.

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.

The clinical spectrum of the anti-phospholipid syndrome (APS) is not limited to vascular thrombosis or miscarriages but includes additional manifestations that cannot be explained solely by a thrombophilic state. Anti-cardiolipin, anti-beta 2 glycoprotein I (anti-β 2 GPI) and lupus anticoagulant (LA) assays are not only the formal diagnostic and classification laboratory tools but also parameters to stratify the risk to develop the clinical manifestations of the syndrome. In particular, anti-β 2 GPI antibodies reacting with an immunodominant epitope on domain I of the molecule were reported as the prevalent specificity in APS patients, correlating with a more aggressive clinical picture. Several laboratory assays to improve the diagnostic and predictive power of the standard tests have been proposed. Plates coated with the phosphatidylserine-prothrombin complex for detecting antibodies represent a promising laboratory tool correlating with LA and with clinical manifestations. Anti-phospholipid antibodies can be found in patients with full-blown APS, in those with thrombotic events or obstetric complications only or in asymptomatic carriers. An inflammatory second hit is required to increase the presence of β 2 GPI in vascular tissues, eventually triggering thrombosis. Post-transcriptional modifications of circulating β 2 GPI, different epitope specificities or diverse anti-β 2 GPI antibody-induced cell signaling have all been suggested to affect the clinical manifestations and/or to modulate their occurrence.

This chapter about the use of antithrombotic agents during pregnancy is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126: 179S-187S). Among the key recommendations in this chapter are the following: for women requiring longterm vitamin K antagonist therapy who are attempting pregnancy, we suggest performing frequent pregnancy tests and substituting unfractionated heparin (UFH) or low molecular weight heparin (LMWH) for warfarin when pregnancy is achieved (Grade 2C). In women with acute venous thromboembolism (VTE), we recommend adjusted-dose LMWH throughout pregnancy or IV UFH for at least 5 days, followed by adjusted-dose UFH or LMWH for the remainder of the pregnancy and at least 6 weeks postpartum (Grade 1C؉). In patients with a single episode of VTE associated with a transient risk factor that is no longer present, we recommend antepartum clinical surveillance and postpartum anticoagulants (Grade 1C). In patients with a single episode of VTE and thrombophilia or strong family history of thrombosis and not receiving long-term anticoagulants, we suggest antepartum prophylactic or intermediate-dose LMWH or minidose or moderate-dose UFH, plus postpartum anticoagulants (Grade 2C). In patients with multiple (two or more) episodes of VTE and/or women receiving long-term anticoagulants, we suggest antepartum adjusted-dose UFH or adjusted-dose LMWH followed by long-term anticoagulants postpartum (Grade 2C). For pregnant patients with antiphospholipid antibodies (APLAs) and a history of two or more early pregnancy losses or one or more late pregnancy losses, preeclampsia, intrauterine growth retardation, or abruption, we suggest antepartum aspirin plus minidose or moder-ate-dose UFH or prophylactic LMWH (Grade 2B). We suggest one of the following approaches for women with APLAs without prior VTE or pregnancy loss: surveillance, minidose heparin, prophylactic LMWH, and/or low-dose aspirin, 75 to 325 mg/d (all Grade 2C). In women with prosthetic heart valves, we recommend adjusted-dose bid LMWH throughout pregnancy (Grade 1C), aggressive adjusted-dose UFH throughout pregnancy (Grade 1C), or UFH or LMWH until the thirteenth week and then change to warfarin until the middle of the third trimester before restarting UFH or LMWH (Grade 1C). In high-risk women with prosthetic heart valves, we suggest the addition of low-dose aspirin, 75 to 162 mg/d (Grade 2C).

We report clinical, neuroimaging and immunological findings in seven women with antiphospholipid antibodies (APLA) and cerebral ischemia. Two patients had systemic lupus erythematosus (SLE) and five had the antiphospholipid syndrome (APS). Autopsies were done in 3 women who died acutely with focal neurological deficits. Evidence for cerebral embolism was found in all patients: a) pathology demonstrated multiple cerebral infarctions and cerebral emboli from underlying non-bacterial thrombotic endocarditis (NBTE) in the patients who died. b) Three patients had thickened mitral valves and embolic cerebral occlusions were identified with cerebral angiography. c) In one patient, echocardiography detected a thrombus on the posterior leaflet of a prolapsing mitral valve at the time of ictus. Our data provide further evidence to implicate valvular endothelium in the genesis of cerebral ischemia in some patients with APLA.

St SW, Rochester, MN 55905. aCL = anticardiolipin antibodies; AI = autoimmune disease; APTT = activated partial thromboplastin time; CA = cancer; DRVVT = dilute Russell viper venom time; DVT = deep venous thrombosis; KCT = kaolin clot time; LA = lupus anticoagulants; PAE = peripheral arterial event; PCT = plasma clot time; PE = pulmonary embolus; PNP = platelet neutralization procedure; SLE = systemic lupus erythematosus; TIA = transient ischemic attack • Objectives: To assess the performance of 4 clotting assays for lupus anticoagulant (LA) detection, to determine the prevalence of LA and anticardiolipin antibodies (aCL), and to correlate LA and aCL prevalence with systemic disease and thrombosis. • Patients and Methods: We studied 664 consecutive patients at the Mayo Clinic in Rochester, Minn, who were referred for laboratory testing because of a clinical suspicion of LA or thrombophilia between June 25, 1990, and July 1, 1991. • Results: Of 664 patients tested for LA, 584 also were tested for aCL. Of patients tested for both LA and aCL, 137 (23.5%) had positive results for one or both tests (13 [9.5%], LA-positive only; 76 [55.5%], aCL-positive only; and 48 [35.0%], positive for both). The dilute Russell viper venom time (DRVVT) was the most frequently positive LA assay (74% of the 61 patients with positive results for LA). Twenty-two patients (36.1% of the 61) had positive results for all 4 LA assays, whereas 21 (34.4% of the 61) had positive results for only 1 LA assay: activated partial thromboplastin time (3 patients [4.9%]), plasma clot time (5 patients [8.2%]), kaolin clot time (5 patients [8.2%]), or DRVVT (8 patients [13.1%]). Thromboembolism prevalence was not definitely associated with positive test results (LA only, aCL only, or LA plus aCL), nor was it strongly associated with aCL isotype or titer. Furthermore, thromboembolism prevalence was not increased when all LA assays were positive, although a history of deep venous thrombosis or pulmonary embolism was nonsignificantly associated with positive results for all 4 LA tests. The likelihood of having both LA-and aCL-positive test results was higher among patients with systemic lupus erythematosus (26 [19.0%] of 137 patients with positive results for one or both tests), but they had no more thrombotic events or fetal loss than other patients in our study group.

The antiphospholipid syndrome (APS) is an acquired thombophilia, which is characterized by one or more thrombotic episodes and obstetric complications in the presence of antiphospholipid (aPL) antibodies (Abs). aPL Abs are detected by laboratory tests such as lupus anticoagulant (LA), anticardiolipin (aCL) and anti-2 -glycoprotein I ( 2 GPI) Abs. This article reviews the most current pathophysiological aspects of APS with emphasis in thrombotic and proinflammatory mechanisms mediated by aPL antibodies.

Essential thrombocytosis is extremely rare in children. However, when present, it is associated with increased prevalence of antiphospholipid antibodies and thrombo-hemorrhagic complications. The authors report here a child with Budd-Chiari Syndrome resulting from essential thrombocytosis and associated antiphospholipid antibodies. A 13- y-old boy presented with microcytic hypochromic anemia, hepatosplenomegaly and thrombocytosis. CT scan demonstrated calcified thrombus in inferior vena cava (IVC). Diagnosis of essential thrombocytosis was considered in view of persistent thrombocytosis, antiphospholipid antibodies, bone marrow showing increased number, clusters and giant forms of megakaryocytes and IVC thrombosis. He was started on warfarin prophylaxis and did not have thrombotic recurrence on follow up.