María Gutierrez Sanchez de la Fuente, MD

Kim Y, Kim SY. Antiphospholipid Antibody and Recurrent Ischemic Stroke: A Systematic Review and Meta-Analysis. Stroke. 2020;51:3728–3732.

Antiphospholipid syndrome (APS) is an autoimmune multisystem disorder characterized by arterial or venous thromboembolic events in the presence of persistent antiphospholipid antibodies (aPL).

aPL are a heterogeneous group of antibodies directed against phospholipid-binding proteins. The aPL detection tests included in APS classification criteria are anticardiolipin (aCL) antibody (immunoglobulin G [IgG] or IgM), anti-beta2-glycoprotein (GP) I antibody (IgG or IgM), and lupus anticoagulant (LA). Based on the International Consensus Criteria for APF, clinically significant aPL profile is defined as the presence of one or more of the following aPLs on two or more occasions at least 12 weeks apart: A positive LA test; aCL IgG or IgM, with a titer >40 units; or/and anti-beta2-GP I IgG or IgM, with a titer >40 units.

Ischemic stroke (IS) and transient ischemic attack (TIA) are the most common neurologic manifestations of APS, and this association is higher in young patients. Based on the Young Stroke Register, patients with IS and APL are at risk to have recurrent stroke; moreover, the Antiphospholipid Antibodies and Stroke Study demonstrated that LA and aCL do not predict subsequent thrombosis after IS. So, the relationship between aPLs and recurrent IS is not clear.

In this article, the authors performed a systematic review and meta-analysis to see the correlation between aPLs and recurrent IS. They included 8 studies, with a total of 2510 patients, 844 aPL positive. Based on the results of this meta-analysis, there is not a statistically significant risk of recurrent IS in the aPL-positive group (RR 1.41, [95% CI, 0.91-2.1]). In the subgroup analysis, there was not an association with patients younger than 50 years (RR 1.91 [95% CI, 0.68-5.35]), neither with aPL type, ethnicity and repeated aPL tests.

The main limitation of this meta-analysis is that the studies included did not have the same aPL cutoff to define positive aPLs (60% considered positive title <20 IgM/IgG antiphospholipid units), so they could not meet the actual criteria for AFS. Another limitation was that most studies only tested for aCL, and 5 of the 8 studies did not have a new determination of aPLs, so the diagnosis of AFS could not have been met in some of the included patients.

With this study, the authors suggest that we need more uniform diagnosis criteria for AFS and an active screening for detecting aPL. New prospective studies are needed to demonstrate a real association between aPLs and recurrent IS, being also for special interest these patients who have positive aPL but do not meet the criteria for diagnosis AFS, and based on the results, choose the best treatment and the best antithrombotic therapy for these patients, as there is not a clear consensus about the management of patients with aPLs/AFS and IS or TIA.