Abstract
Prothrombin fragment F1 + 2 (F1 + 2) and thrombin–antithrombin (TAT) have been assessed
in antiphospholipid syndrome (APS) but without evaluating a direct relationship with
antiphospholipid (aPL) antibody titers. This article aims to investigate a direct
relationship between aPL and F1 + 2 and perform a systematic review and meta-analysis
of F1 + 2 and TAT in APS. Systematic search was performed using EMBASE and PubMed
databases from January 1982 to December 2018 and random effects meta-analyses for
continuous outcomes. This is a cross-sectional case–control study; immunoglobulin
G/immunoglobulin M (IgG/IgM) anticardiolipin (aCL) anti-β2-glycoprotein-I, antiprothrombin (aPT) antibodies, F1 + 2, and lupus anticoagulants
(LA) were measured in 25 thrombotic primary APS (PAPS), 9 nonthrombotic carriers of
aPL, and 18 controls. The significant effect size (ES) for F1 + 2 between aPL +ve
and aPL −ve systemic lupus erythematosus (SLE) and between aPL +ve SLE and control
displayed high heterogeneity. The significant ES for F1 + 2 between aPL −ve SLE and
controls displayed no heterogeneity. The ES for TAT between aPL +ve and aPL −ve SLE
patients and between aPL −ve SLE and controls was low, without heterogeneity. Mean
F1 + 2 was greater in PAPS (p < 0.0001), inversely correlated with IgG aCL, IgM aPT, and LA (p = 0.001, 0.03, and 0.01, respectively), though only IgG aCL negatively predicted
F1 + 2 (p = 0.01). IgG aCL inversely predicts F1 + 2. IgG aCL positivity introduces heterogeneity
in the F1 + 2 ES, whereas the lack of heterogeneity in the ES for TAT may indicate
poor TAT formation in aPL +ve group. Thus, F1 + 2 measurements may be unfounded as
already demonstrated for TAT in the 1990s.
Keywords
antiphospholipid antibodies - prothrombin fragment 1 + 2 - thrombin–antithrombin
