Novel Insights Into Pathogenesis, Diagnosis and Treatment of Antiphospholipid Syndrome

Sonali Wijetilleka; Tina Scoble; Munther Khamashta

Curr Opin Rheumatol. 2012;24(5):473-481.

Abstract and Introduction

Abstract

Purpose of review To provide an update of recent insights into the pathogenesis, diagnosis and treatment of antiphospholipid syndrome (APS) from current literature.
Recent findings β2GPI was recently implicated in the pathogenesis of thrombosis. High titres of anti-β2GPI antibodies are present in patients with triple positivity which highlight its importance. Consensus guidelines have been published to standardise diagnostic assays and once implemented may yield more accurate diagnoses of APS. An 'aPL score' has been formulated to improve the detection and outcomes of patients. New oral anticoagulants, statins and concomitant therapy with warfarin and aspirin have been identified as potential novel therapeutic interventions for thrombotic APS. Advances in the pathogenesis of obstetric APS have occurred, such as the concept of redefining the syndrome as inflammatory and clearer identification of the roles of complement, β2GPI and annexin 5. Independent risk factors for pregnancy failure have been recognised and when combined with clinical and laboratory features may improve patient outcomes. Interventions involving adjusted doses of low molecular weight heparin in combination with aspirin have shown promising results from initial studies.
Summary Recent insights into the pathogenesis of APS have unveiled novel areas for treatment intervention. Diagnostic criteria and recommendations have been revised and formulated to provide consensus and standardisation for diagnosis.

Introduction

Recent changes to the management and diagnosis of antiphospholipid syndrome (APS) and the current opinions regarding pathogenesis have progressed over the last 12 months. In this article, we aim to provide an update of the novel insights in both thrombotic and obstetric APS.

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Table 1. Thromboprophylaxis regimes for patients with established antiphospholipid syndrome (based on current guidelines) ^2,44
Patients with definite APS and first venous event	Anticoagulant therapy with warfarin to a target INR of 2.0–3.0 indefinitely. Duration of treatment is limited to 3–6 months in patients with low risk aPL profile and other precipitating factors.
Patients with definite APS and arterial events	Increase target INR to above >3.0 on warfarin therapy or commence treatment with concomitant anticoagulant (target INR of 2.0–3.0) and antiaggregant (aspirin). Clinicians must gauge the patient's bleeding risk before commencing this regimen.
Patients with recurrent refractory thromboses	Consider statins, hydroxychloroquine or low molecular weight heparin in refractory cases.

APS, antiphospholipid syndrome.

Table 2. Suggested treatment regimens for antiphospholipid syndrome in pregnancy (revised from [2])
Patients with APS without previous, thrombosis and recurrent early (pre-embryonic or embryonic) miscarriage	Low-dose aspirin monotherapy or low-dose aspirin in combination with either UFH (5000–7500 IU subcutaneously every 12 h) or LMWH (usual prophylactic dose)
Patients with APS without previous thrombosis and fetal death (more than 10 weeks' gestation) or previously early delivery (<34 weeks gestation) due to severe preeclampsia or placental insufficiency	Low-dose aspirin and: UFH (In the first trimester 7500–10 000 IU subcutaneously every 12 h; in the second and third trimesters 10000U subcutaneously every 12 h, or every 8–12 h adjusted to maintain the mid-interval aPTT^a 1.5 times the control mean) LMWH (usual prophylactic dose)
Patients with APS with thrombosis	Low-dose aspirin and: UFH (subcutaneously every 8–12h adjusted to maintain the mid-interval aPTT or heparin concentration (anti-Xa activity)^a in the therapeutic range) LMWH (usual therapeutic dose e.g., enoxaparin 1 mg/kg subcutaneously, or dalteparin 100 U/kg subcutaneously every 12 h, or enoxaparin 1.5 mg/kg per day subcutaneously, or dalteparin 200 U/kg per day subcutaneously

APS, antiphospholipid syndrome; aPTT, activated partial thromboplastin time; LDA, low-dose aspirin; LWMH, low molecular weight heparin; UFH, unfractionated heparin. All patients should receive aspirin and LMWH for 6 weeks postpartum. Patients with thrombosis should be re-started on warfarin postpartum.
^aWomen without lupus anticoagulant in whom the aPTT is normal can be monitored with aPTT, however, women with lupus anticoagulant should be monitored with antifactor Xa activity.

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