Elsevier

Journal of Autoimmunity

Volume 33, Issue 2, September 2009, Pages 92-98
Journal of Autoimmunity

Review
Management of antiphospholipid syndrome

https://doi.org/10.1016/j.jaut.2009.05.002Get rights and content

Abstract

Antiphospholipid syndrome (APS) is characterised by vascular thrombosis and/or obstetric morbidity in the presence of persistently positive antiphospholipid antibodies (aPL). Balancing an individuals' risk of thrombosis against the benefits and risks of antithrombotic therapies is crucial for optimising management and preventing morbidity in APS and asymptomatic aPL. Limitations in research studies have led to debate regarding best-practice. This review of the available literature makes the following recommendations. Those with asymptomatic aPL should only be treated with aspirin if they have persistently positive aPL, obstetric APS, or co-existent systemic lupus erythematosus. For those with APS, lower risk patients (i.e. first venous thrombosis) should be treated with warfarin to an INR 2.0–3.0. Those at higher risk (i.e. arterial thrombosis or recurrent events) should be treated with warfarin to an INR of >3.0. During pregnancy in APS, low molecular weight heparin (LMWH) and aspirin should be used and women should be under the care of obstetricians and physicians specialising in APS. Additional vascular and thrombotic risk factors should be actively reduced in all patient groups. Further randomised controlled trials are required, which should involve larger patient groups with APS diagnosed according to accepted criteria. This may mean that international and multi-centre trials are needed to ascertain the best treatment regimens.

Introduction

Antiphospholipid syndrome (APS) is an autoimmune disorder characterised by vascular thrombosis and/or obstetric morbidity in the presence of persistently positive antiphospholipid antibodies (aPL), measured at least 12 weeks apart [1]. Many individuals can be aPL positive without thrombosis or obstetric morbidity. This does not indicate APS, although these individuals are at an increased risk of developing the syndrome.

In addition to thrombosis and obstetric manifestations, other clinical features of APS include abnormalities of skin, cardiac valves, central nervous system, kidneys, and haematological abnormalities such as thrombocytopaenia [2].

The management of aPL positive patients centres on antithrombotic therapies and anticoagulation. However, as is frequently the case in autoimmune conditions, limitations in research studies have led to debate about best-practice. Randomised controlled trials (RCTs) have encountered difficulties recruiting sufficiently large groups of patients to represent the spectrum of the syndrome. Consequently, methodologically weaker observational studies have formed the main basis of evidence-based practice as they are able to recruit larger sample sizes and non-selected patients. Additionally there is a lack of laboratory standardisation for aPL. As a result, RCTs and observational studies have often reached different conclusions.

Section snippets

Quantifying the risk posed by aPL

To determine therapeutic benefit, it is essential to quantify risk as, although those with aPL are at a high risk of morbidity, they are commonly young, may be asymptomatic, and the risks of antithrombotic therapies are not insignificant. Therefore the key to optimal management and prevention of morbidity in both APS and asymptomatic aPL entails balancing an individuals' risk of thrombosis against the benefits and risks induced by antithrombotic therapies. An individual's thrombotic risk is

Is there a role for primary thromboprophylaxis in asymptomatic aPL carriers?

Unfortunately many patients are recognised as having aPL only after a thrombotic event has occurred. Given the increased risk of thrombosis in asymptomatic aPL positive individuals, primary prevention is imperative if these individuals are to avoid significant morbidity. Aspirin has been the logical starting point for thromboprophylaxis, however studies have drawn conflicting conclusions.

Several retrospective studies have been conducted. Erkan et al. [10] performed a cross-sectional study which

Secondary thromboprophylaxis in APS

Those who have had a thrombotic event in the presence of persistently positive aPL, i.e. those with APS, are at a high risk of recurrence of thrombotic complications. The initial thrombotic event should be managed routinely, independent of aPL positivity. For venous events, heparin (usually low-molecular weight) is recommended, followed by warfarin. For arterial events, antiaggregation is commonly used as aPL status may be unknown. It is the subsequent management that is imperative for reducing

Management of pregnancy in APS

Complications during pregnancy are common in APS and include maternal thrombosis, recurrent spontaneous abortions before 10 weeks gestation, and late adverse pregnancy outcomes such as foetal death, pre-eclampsia, foetal growth restriction, and pre-term birth. Even with optimal management the live birth rate for women with APS remains around 80% [39], [40], [41], and adverse outcomes occur in a “refractory” 20–30% of cases [42].

Pre-pregnancy and antenatal care in APS is crucial for minimising

Conclusion

Fig. 1, Fig. 2, Fig. 3 illustrate our current recommendations regarding pharmacological management of thrombotic and obstetric APS. Large multicenter, randomised clinical trials are needed to confirm and expand evidence regarding the efficacy of various therapeutic interventions in APS.

References (64)

  • W.H. Kutteh

    Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone

    Am J Obstet Gynecol

    (1996)
  • R.G. Farquharson et al.

    Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment

    Obstet Gynecol

    (2002)
  • R. Rai et al.

    Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment

    Obstet Gynecol

    (2002)
  • L.S. Noble et al.

    Antiphospholipid antibodies associated with recurrent pregnancy loss: prospective, multicenter, controlled pilot study comparing treatment with low-molecular-weight heparin versus unfractionated heparin

    Fertil Steril

    (2005)
  • M.D. Stephenson et al.

    Treatment of antiphospholipid antibody syndrome (APS) in pregnancy: a randomized pilot trial comparing low molecular weight heparin to unfractionated heparin

    J Obstet Gynaecol Canada

    (2004)
  • D.W. Branch et al.

    A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group

    Am J Obstet Gynecol

    (2000)
  • M.D. Lockshin et al.

    Prednisone does not prevent recurrent fetal death in women with antiphospholipid antibody

    Am Obstet Gynecol

    (1989)
  • F.S. Cowchock et al.

    Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment

    Am J Obstet Gynecol

    (1992)
  • R.K. Silver et al.

    Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients

    Am J Obstet Gynecol

    (1993)
  • T.T. Horlocker et al.

    Regional anesthesia in the anticoagulated patient: defining the risks (the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation)

    Regional Anesth & Pain Med

    (2003)
  • E.N. Harris et al.
  • A. Martinez-Berriotxoa et al.

    Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus

    Lupus

    (2007)
  • G. Finazzi

    Aspirin in asymptomatic patients with confirmed positivity of antiphospholipid antibodies?

    Intern Emerg Med

    (2008)
  • P. Vila et al.

    Prevalence, follow-up and clinical significance of the anticardiolipin antibodies in normal subjects

    Thromb Haemost

    (1994)
  • J.A. Giron-Gonzalez et al.

    Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals

    J Rheumatol

    (2004)
  • N.M. Shah et al.

    Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients

    Lupus

    (1998)
  • D. Erkan et al.

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

    Rheumatology

    (2002)
  • M.H. Rosove et al.

    Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients

    Ann Intern Med

    (1992)
  • M.A. Khamashta et al.

    The management of thrombosis in the antiphospholipid-antibody syndrome

    N Engl J Med

    (1995)
  • S. Krnic-Barrie et al.

    A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis

    Arch Intern Med

    (1997)
  • C. Kearon et al.

    A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism

    N Engl J Med

    (1999)
  • G. Ruiz-Irastorza et al.

    A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies

    Arthritis Rheum (Arthritis Care Res)

    (2007)
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      The same authors recently investigated pregnancy outcome of SLE women with or without aPL and found that the rate of adverse pregnancy outcome was 15.4% in patients without aPL vs 43.8% in patients with aPL, and LAC was found to be an independent predictor of adverse pregnancy outcome [47]. In terms of treatment for APS [70,71], low dose aspirin (LDA) is most commonly used for obstetric prophylaxis, but experts also recommend that addition of low molecular weight heparin (LMWH) in specific circumstances such as older maternal age, high-risk aPL profile, and assisted reproductive techniques [72]. Lazzaroni et al. [6] suggest that pregnancy in SLE with a high-risk aPL profile should be treated with prophylaxis for both maternal and fetal protection while those with a low-risk profile can be treated using a less aggressive approach.

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