Management of the antiphospholipid syndrome

Antiphospholipid antibodies are associated with a hypercoagulable state leading to a wide variety of systemic manifestations and obstetric complications. The different pathologic manifestations can be a result of arterial and venous thrombosis, microthrombotic angiopathy, embolization, obstetric disease, and non-thrombotic phenomenon. Presently, the treatment centers on anticoagulation. Two randomized prospective studies in patients with antiphospholipid syndrome with initial thromboembolic event support the target international normalized ratio of 2.0 to 3.0 for the prevention of future thrombotic events. With pregnancy, the combination of aspirin and heparin is still the standard of care. In addition, nonthrombotic features and any associated autoimmune disease may need to be treated. Underlying risk factors precipitating the thromboembolic phenomenon need to be addressed as well.     

Management of antiphospholipid syndrome in pregnancy

APS pregnancy losses are one of the most common treatable causes of recurrent pregnancy loss. Clinical trials have helped in delineating the dangers of prednisone use in pregnancy, and suggest that heparin and aspirin regimens are preferred. However, the clinical trials suffer from the lack of uniform definition of antiphospholipid antibody positivity, from inclusion of women with different past pregnancy histories, and from different timing of the onset of the therapeutic modalities tested. New research on the role of complement activation in murine APS pregnancy loss may change therapeutic options in the future.     

Management of pregnancy in antiphospholipid syndrome

Pregnant women with APS are at high risk of maternal and fetal pregnancy complications. Multidisciplinary teams expert in this condition should coordinate management. Even with current management strategies, the risk of maternal thrombosis, fetal loss, or other adverse obstetric outcomes remains. Close monitoring of the various aspects of this condition may reduce maternal morbidity and improve fetal outcome. The pathogenesis of the adverse pregnancy outcome in APS has not yet been fully elucidated, although active research in this field continues. Until this is ascertained, we must accept that many aspects of management are purely empiric, and it is our duty to counsel patients thoroughly so that they understand the risks and benefits of the treatment options they are offered.     

Management of thrombosis in antiphospholipid antibody syndrome

Antiphospholipid antibody positive patients are at risk for venous and arterial thrombosis. The risk of recurrent thromboembolism is high. Although the standard of care is high-intensity warfarin after a thromboembolic event, some studies indicate that this degree of anticoagulation is not needed. There is an urgent need of clinical trials to address management of thrombosis in antiphospholipid syndrome.     

Pediatric antiphospholipid antibodies and antiphospholipid syndrome

Antiphospholipid syndrome (APS) can occur in children, like adults, with the same diverse spectrum of thrombotic sites but predominately with deep vein thrombosis and stroke. In contrast with adults, however, transient nonthrombogenic antiphospholipid (aPL) antibodies are seen more commonly, usually after childhood infections. In those with "true" aPL antibodies, recurrent thrombotic events seem less frequent than in adults, perhaps reflecting the less prothrombotic hemostatic state of childhood. Children with thrombotic events in APS present difficult management problems, as there is little evidence-based medicine. The duration and intensity of anticoagulation are unresolved management issues, but a target international normalized ratio of 2 to 3 is used by most. Multicenter randomized controlled trials would provide answers to some of these issues but are difficult to organize due to ethical issues and the rarity of the condition. A pediatric APS registry such as the Ped-APS Register is more easy to organize and can yield informative data.     

Systemic antiphospholipid syndrome

The antiphospholipid syndrome (APS) was reported in the early 1980s as a triad of manifestations. Since than it became one of the most systemic conditions. Almost any organ and tissue may be involved in the disease, including the brain, the heart, the placenta, the endocrine system, the blood, the kidneys and many more. In the article it is suggested to add to the syndrome the word systemic in analogy to its sister condition, systemic lupus erythematosus.     

Neonatal antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a clinical entity characterized by arterial and venous thrombosis, adverse obstetric outcome and the presence of antibodies against phospholipids in serum or plasma. The objective of the present study is to describe a rare case of APS that occurred in a neonate born from a patient previously diagnosed as primary APS. A male, preterm born twin infant, whose mother had been diagnosed as primary APS, developed thrombocytopenia, livedo reticularis, pericardial effusion and thrombosis of the left subclavian and external jugular veins concomitantly with severe respiratory tract infection soon after his delivery, that culminated with his death two months after the birth, in spite of the large spectrum antibiotic therapy and all supportive measures. Laboratory findings included high titers of IgM anticardiolipin antibodies and moderate titers of IgG isotype and negative antinuclear antibody, configuring a case of neonatal APS. Neonatal APS is a rare clinical condition, with only a few cases described in the literature. Its occurrence may depend on the passage of antibodies through the placenta or, as it seems to have occurred in the present case, by the production of de novo antibodies by the fetus. The present case illustrates the necessity of a higher surveillance of the neonates born from mothers with primary APS or systemic lupus erythematosus (SLE) for the eventual development of such complication.     

Catastrophic antiphospholipid syndrome

Catastrophic APS is a potentially life-threatening condition with a high mortality, which requires high clinical awareness. New mechanisms for its production can only be explored if samples are obtained, stored, and dis-patched to investigation sites in Europe (Barcelona), the United States (Atlanta), and Japan (Sapporo). Details will be posted and made available on the International Registry Web Site in 2006. It is essential that the condition be diagnosed early and treated aggressively. The combination of high doses of iv heparin, iv steroids plus repeated doses of iv gammaglobulins or plasma exchange is the treatment of choice in patients with this severe condition. Additionally, preventive measures in patients with APS may be effective if the development of the catastrophic APS is to be avoided.     

Pediatric antiphospholipid syndrome

APS is rare in the pediatric age, but it represents an interesting phenomenon because most of the known "second hit" risk factors such as atherosclerosis, smoking, hypertension, contraceptive hormonal treatment, and pregnancy are not present in childhood. This could also be the reason for the prevalence of some clinical manifestations rather than others in PAPS.On the other hand, the increased frequency of infectious processes in the childhood age is likely responsible for the relatively high prevalence of non-pathogenic and transient aPL. Such points raise the problem of a different diagnosis or monitoring approach in pediatric APS. Of particular interest is the special entity of neonatal APS, which represents an in vivo model of acquired autoimmune disease, in which transplacentally acquired aPL cause thrombosis in the newborn. International registries for pediatric and neonatal APS are currently in place; epidemiologic, clinical, and laboratory re-search will help to shed light on all the still obscure aspects of this fascinating but rare disorder in the very young. Finally, treatment is less aggressive overall in pediatric APS, given the reluctance to anticoagulate children over the long term. Studies on the outcome of pediatric APS and the relative risks of prolonged anticoagulation in children are necessary to determine the type and duration of anticoagulation therapy.     

'Catastrophic' antiphospholipid syndrome

When 'catastrophic' is applied as an adjective to the antiphospholipid syndrome, it implies a characteristic presentation due to predominantly small blood vessel thrombosis leading to rapidly progressive failure of multiple organs and a frequently fatal outcome. We present the case of a 48-year-old woman who presented with the 'catastrophic' antiphospholipid syndrome without previous history of coagulation disorder or connective tissue disease that illustrates the difficulties in diagnosing and managing this disorder. We also review the factors that have been reported to have a role in the development of this condition and show how this case throws light on its pathogenesis.     

Catastrophic antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a thrombotic disorder associated with autoantibodies that target membrane phospholipids and phospholipid-binding proteins, which regulate coagulation. APS is usually characterized by major arterial or venous occlusions, pregnancy complications, or both. In 1992, Asherson described an unusual variant of APS termed the catastrophic antiphospholipid syndrome (also known as Asherson's syndrome), the hallmark of which is rapid multiorgan failure caused by widespread small-vessel thrombi. Empiric treatments have improved the prognosis of patients, but half still die from thrombotic diathesis, even though those who survive the acute stages frequently remain well. Given the persistently high mortality rate, efforts have been underway to facilitate early diagnosis, institute effective treatments in a timely manner and to better understand the cause (or causes) of this extreme condition in order to improve outcomes.     

Catastrophic antiphospholipid syndrome

Catastrophic antiphospholipid syndrome, defined and documented in 1992, is a potentially fatal complication seen in patients with antiphospholipid antibody. It may arise de novo in patients not previously suspected as having an antiphospholipid syndrome, or it may complicate the course of patients currently treated for this syndrome. Precipitating or “trigger” factors have been identified in 55% of patients; the most common of these factors is infection. The precipitating factors should be avoided or energetically treated in patients with the antiphospholipid syndrome in order to prevent this “catastrophic” course. The clinical manifestations are those of multiorgan failure, and unusual vessels or organs can be involved. Treatment of the condition, with emphasis on effective anticoagulation, intravenous steroids, intravenous immunoglobulin, or plasma exchange, should be aggressive to achieve a satisfactory outcome. Regrettably, despite all available therapeutic options at this time, the mortality is still high (greater than 50%).     

Diagnosis of antiphospholipid syndrome

Antiphospholipid syndrome is a multisystem autoimmune disease, characterized by recurrent vascular thrombosis and/or pregnancy losses in the presence of persistently positive antiphospholipid antibodies. In clinical practice, testing for anticardiolipin antibodies and lupus anticoagulant is mandatory for the laboratory diagnosis of antiphospholipid syndrome. Identification of patients with antiphospholipid syndrome is important, as prophylactic anticoagulant therapy may prevent thrombosis from recurring, and treatment during pregnancy can improve fetal and maternal outcome.     

Catastrophic antiphospholipid syndrome

Catastrophic antiphospholipid syndrome is a life-threatening subset of antiphospholipid syndrome. It is defined by the involvement of at least three different organ systems over a period of days or weeks. This review focuses on the basic pathobiology and current concepts in the management of this rare but important disorder.