Why Antiphospholipid Antibody Syndrome Should Be On Your Radar

In a recent multicenter, population-based case–control study of 582 stillbirths and 1,547 live births, Silver et al found that elevated levels of aCL and anti-β2GPI antibodies were associated with an approximate threefold to fivefold increased odds of stillbirth. The authors suggested consideration of testing for aPLs in cases of otherwise unexplained stillbirth.²²

APS ACTION

Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) is the first international research network created specifically to design and conduct large-scale, multi-center clinical trials in persistently aPL-positive patients. The network has launched two important collaborative international projects. The first is a randomized controlled trial of hydroxychloroquine in the primary thrombosis prevention of persistently aPL-positive, thrombosis-free patients without systemic autoimmune diseases. The second is a web-based registry of aPL-positive patients with or without systemic autoimmune diseases, which will also include annual blood collection for aPL testing and future basic science studies.²³

Treatment

It is not surprising that management of aPL-positive patients focuses on anticoagulation and antithrombotic therapies. However, due to the low prevalence of the disease, randomized controlled trials have faced limitations in recruiting sufficient participants to represent the wide spectrum of the disease and thus empower the study design. As a consequence, much of the evidence-based practice in the management of APS has relied on the methodologically weaker observational studies. This has led to controversy and debate regarding what the best practices should be. Recent consensus recommendations have been published for the prevention and long-term management of thrombosis in aPL-positive patients.^6,17

Anticoagulation with warfarin forms the cornerstone of conventional therapy in aPL-induced thrombosis. It is agreed that therapy should be indefinite, with a target internationalized normal ratio (INR) of 2.0–3.0.²⁴ Patients with arterial thrombosis should be managed with either combined anticoagulant antiaggregant therapy, such as aspirin (INR 2.0–3.0), or treatment with warfarin alone (INR > 3.0). The patient’s bleeding risk should be evaluated carefully before commencing anticoagulant therapy.¹⁷

Prevention of Pregnancy Loss

With proper management, including preconceptional counseling and pharmacological treatment, more than 75% of pregnant women with aPLs will deliver a viable, healthy infant. However, pregnancy should be carefully planned. Women with either severe pulmonary hypertension or those who have suffered a recent thrombotic event, particularly stroke, should be discouraged from conceiving.²⁵