Elsevier

The Lancet

Volume 376, Issue 9751, 30 October–5 November 2010, Pages 1498-1509
The Lancet

Seminar
Antiphospholipid syndrome

https://doi.org/10.1016/S0140-6736(10)60709-XGet rights and content

Summary

The antiphospholipid syndrome causes venous, arterial, and small-vessel thrombosis; pregnancy loss; and preterm delivery for patients with severe pre-eclampsia or placental insufficiency. Other clinical manifestations are cardiac valvular disease, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, and cognitive impairment. Antiphospholipid antibodies promote activation of endothelial cells, monocytes, and platelets; and overproduction of tissue factor and thromboxane A2. Complement activation might have a central pathogenetic role. Of the different antiphospholipid antibodies, lupus anticoagulant is the strongest predictor of features related to antiphospholipid syndrome. Therapy of thrombosis is based on long-term oral anticoagulation and patients with arterial events should be treated aggressively. Primary thromboprophylaxis is recommended in patients with systemic lupus erythematosus and probably in purely obstetric antiphospholipid syndrome. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin. Hydroxychloroquine is a potential additional treatment for this syndrome. Possible future therapies for non-pregnant patients with antiphospholipid syndrome are statins, rituximab, and new anticoagulant drugs.

Section snippets

Pathogenesis

The term antiphospholipid syndrome was coined in the early 1980s to describe a unique form of autoantibody-induced thrombophilia, whose hallmarks are recurrent thrombosis and pregnancy complications.1 The clinical spectrum of this syndrome has widened,2, 3 with important advances in the knowledge of its pathogenesis and clinical management made during the past several years.

Research shows the central role of endothelial cells, monocytes, platelets, and complement in induction of thrombosis and

Epidemiology

The likelihood that an antiphospholipid antibody contributes to the pathogenesis of thrombosis or pregnancy complications, or both, varies between clinical settings. About 40% of patients with systemic lupus erythematosus have antiphospholipid antibodies,17 but less than 40% of them will eventually have thrombotic events.18, 19 However, thrombotic antiphospholipid syndrome is regarded as a major adverse prognostic factor in patients with lupus.18 In the general population, antiphospholipid

Clinical manifestations

Panel 1 shows the main clinical manifestations of antiphospholipid syndrome. Thromboses are one of the hallmarks of this syndrome, and venous thrombosis, or embolism, is the most frequent manifestation.2 However, by contrast with thromboses associated with congenital thrombophilias, those associated with antiphospholipid syndrome might also occur in any vascular bed.2 In the arterial bed, the CNS is most generally affected,2 usually in the form of stroke or transient ischaemic attacks.

Classification criteria and risk stratification

In 1998, the preliminary classification criteria for antiphospholipid syndrome were proposed at Sapporo, Japan.45 Classification for this syndrome needed at least one clinical manifestation together with positive tests for circulating antiphospholipid antibodies, including lupus anticoagulant or anticardiolipin, or both, at medium-high values, detected at least twice in 6 weeks.

In 2006, classification criteria were updated (panel 2).46 Essentially, the clinical criteria remained unchanged;

Management of thrombosis

Prevention of thrombosis is a major goal of therapy in patients with antiphospholipid antibodies. There are two different clinical settings: patients with antiphospholipid syndrome who have already had a thrombotic event (secondary thromboprophylaxis); and antiphospholipid antibody carriers without previous thrombosis, which can be either purely asymptomatic individuals, patients with systemic lupus erythematosus, or women with obstetric antiphospholipid syndrome (primary thromboprophylaxis).

Pregnancy management

With proper management, more than 70% of pregnant women with antiphospholipid syndrome will deliver a viable live infant.81 Ideally, preconception counselling gives the physician the opportunity to understand the specific context of each patient with the syndrome and to outline the risks of pregnancy and treatment. Pregnancy should be discouraged in all women with important pulmonary hypertension because of the high risk of maternal death,82 and should be postponed in the setting of

Future therapies

Several potential new therapeutic approaches for antiphospholipid syndrome are emerging (panel 3). Antiplatelet drugs other than aspirin have been used only rarely in patients with this disorder.105 However, combination treatment with aspirin plus dipyridamole and aspirin plus clopidogrel have shown higher efficacy than has aspirin alone in patients with stroke106 or atrial fibrillation,107 respectively. Such combinations might be considered in selected patients with antiphospholipid syndrome

Search strategy and selection criteria

In this Seminar we aimed to offer an up-to-date view of the main pathophysiological, clinical, diagnostic and therapeutic advances in the discipline of the antiphospholipid syndrome. The literature search was done from January, 2005, to January, 2010. The PubMed database was used with the medical subject heading terms “antiphospholipid syndrome” OR “antibodies, antiphospholipid” OR “lupus coagulation inhibitor”. Embase search included the terms “antiphospholipid syndrome”, “lupus

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