title: Risk of thrombosis in patients with primary immune thrombocytopenia and antiphospholipid antibodies: A systematic review and meta-analysis.
abstract: Antiphospholipid antibodies (aPL) are common in ITP, but their role for the occurrence of ITP-related thrombosis is controversial. We performed a systematic review and a meta-analysis to investigate the risk of thrombosis associated with lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2GP-I antibodies in primary ITP. The literature search was run on Medline, Cochrane and ISI Web of Science from January 1st 1980 to December 31st 2014. Unpublished studies were searched in meeting abstracts. The main analysis assessed the risk of all thromboses (arterial or venous) associated with the presence of LA, aCL or anti-β2GP-I antibodies. Random-effect models were used to calculate odds ratios (OR) and their 95% confidence intervals (CI). Searches in electronic databases retrieved 776 citations. Twelve additional studies from unpublished literature were added. Eventually, 10 cohort studies totalizing 1574 patients were included in the analysis. The pooled OR for the risk of all thromboses associated with LA was 6.11, 95% CI [3.40-10.99]; it was 2.14, 95% CI [1.11-4.12] with aCL. The ORs were similar when stratifying on the type of thrombosis (arterial vs. venous). Only two studies assessed the risk of thrombosis associated with anti-β2GP-I antibody positivity; consequently, no pooled OR was computed for these antibodies. This meta-analysis highly suggests that LA positivity, and to a less extent aCL antibodies, are associated with an enhanced risk of thrombosis in primary ITP patients. Further prospective studies are needed to identify the factors associated with the risk of thrombosis among LA patients before assessing prevention strategies.
authors.affiliation: Internal Medicine Department, Toulouse University Hospital; UMR 1027 Inserm-University of Toulouse; CIC 1436, Toulouse University Hospital, France. Electronic address: guillaume.moulis@univ-tlse3.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Moulis
authors.affiliation: Internal Medicine Department, Caen University Hospital, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Audemard-Verger
authors.affiliation: Inserm UMRS 1136 Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnaud
authors.affiliation: Rheumatology Department, Toulouse University Hospital, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Luxembourger
authors.affiliation: Clinical and Medical Pharmacology Department, Toulouse University Hospital, UMR 1027 Inserm-University of Toulouse, France.
authors.forename: François
authors.initials: F
authors.lastname: Montastruc
authors.affiliation: Department of Pathophysiology, University of Medicine and Pharmacy of Craiova; Department of Hematology, Filantropia City Hospital, Craiova, Romania.
authors.forename: Amelia Maria
authors.initials: AM
authors.lastname: Gaman
authors.affiliation: Rheumatology Unit, Department of Medicine Solna, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Svenungsson
authors.affiliation: Department of Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ruggeri
authors.affiliation: Department of Internal Medicine, French National Center for Autoimmune Cytopenias, Créteil, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Mahévas
authors.affiliation: Department of Internal Medicine, Lyon University Hospital, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gerfaud-Valentin
authors.affiliation: GlaxoSmithKline, Clinical Research, RD Projects Clinical Platforms & Sciences, Collegeville, PA, United States.
authors.forename: Andres
authors.initials: A
authors.lastname: Brainsky
authors.affiliation: Department of Internal Medicine, French National Center for Autoimmune Cytopenias, Créteil, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Michel
authors.affiliation: Department of Internal Medicine, French National Center for Autoimmune Cytopenias, Créteil, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Godeau
authors.affiliation: Clinical and Medical Pharmacology Department, Toulouse University Hospital, UMR 1027 Inserm-University of Toulouse, France.
authors.forename: Maryse
authors.initials: M
authors.lastname: Lapeyre-Mestre
authors.affiliation: Internal Medicine Department, Toulouse University Hospital; UMR 1027 Inserm-University of Toulouse; CIC 1436, Toulouse University Hospital, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Sailler
mesh_terms: D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology; D006801:Humans; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000150:complications / Q000276:immunology*; D012306:Risk; D013927:Thrombosis / Q000150:complications / Q000276:immunology*
chemical_list: D017152:Antibodies, Antiphospholipid