ReviewManagement of antiphospholipid syndrome
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.
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Cited by (63)
Treatment of antiphospholipid syndrome
2020, Systemic Lupus Erythematosus: Basic, Applied and Clinical AspectsSafety issues and recommendations for successful pregnancy outcome in systemic lupus erythematosus
2018, Journal of AutoimmunityCitation Excerpt :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.
Treatment of Pregnancy Complications in Antiphospholipid Syndrome
2017, Handbook of Systemic Autoimmune DiseasesTreatment of Antiphospholipid Syndrome
2016, Systemic Lupus Erythematosus: Basic, Applied and Clinical Aspects