Impact of Persistent Antiphospholipid Antibodies on Symptomatic Thromboembolism In Children: A Systematic Review & Meta-Analysis [Observational Studies]
Authors: Kenet Gili , Bonduel Mariana , Chan Anthony , Goldenberg Neil , Holtzhauer Suzzane , Iorio Alfonso , Journeycake Janna M. , Junker Ralf , Male Christoph , Massicotte Mary Patricia , Mesters Rolf M. , Monagle Paul , Van Ommen Heleen , Raffini Leslie , Simioni Paolo , Young Guy , Nowak-Gottl Ulrike 
Published: October 2019

Abstract
Abstract 3169

Background:
Adapted from the adult definition, pediatric antiphospholipid syndrome [APS] has been defined as one or more arterial or venous thrombosis associated with persistent antiphospholipid antibodies, i.e. IgM or IgG anticardiolipin antibodies [ACL: cut-off > 99th age-dependent percentile] or the presence of lupus anticoagulants confirmed in at least one follow-up visit more than 8 to 12 weeks apart. Antiphospholipid antibodies play an important role in the development of pediatric thromboembolism [TE] with arterial TE or stroke being more often associated with primary APS compared to deep venous thrombosis [DVT], which is observed predominantly in children with secondary APS. However, results of single studies on the risk thromboembolism onset associated with APS have been contradictory or inconclusive, mainly due to lack of statistical power. The aim of this study was to estimate the impact of APS on risk of childhood arterial and venous TE via meta-analysis of published observational studies.

Methods:
A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2010 was conducted using key words in combination both as MeSH terms and text words. Citations were independently screened by two authors and those meeting the a priori defined inclusion criteria were retained. Data on year of publication, study design, laboratory methodologies, country of origin, number of patients/controls, ethnicity, type and location of TE were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed-effects and random-effects models.

Results:
Eight of 319 (DVT) and seven out of 185 (arterial TE) references found met inclusion criteria: In total 1403 patients and 1904 population-based controls aged neonate to 18 years were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. In addition, regression analysis did not reveal statistical significant differences between locations of TE, age at first disease onset, study country, or publication year. Thus, data from arterial and venous TE were analyzed together. A statistically significant association with a first TE onset was demonstrated with a cumulative summary ORs/CIs (fixed-effects model) of 5.9/3.6-9.7.

Conclusions:
The present meta-analysis indicates that APS serves as a clinical meaningful risk factor for a first symptomatic TE in children. However, the impact of APS upon outcome and recurrence risk needs to be further investigated.

Disclosures:
No relevant conflicts of interest to declare.