Validity of Coagulation Activation Markers in Antiphospholipid Syndrome: A Systematic Review and Meta-analysis with a Short Data Report

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.

How We Interpret Thrombosis with Thrombocytopenia Syndrome?

“…Furthermore, as a characteristic of coagulation and fibrinolysis testing, APTT is prolonged in LA-positive cases [93]. FDP, D-dimer, and the coagulation activation marker TAT are elevated to varying degrees in the presence of active thrombosis [104]. In other words, if the platelet count is decreased and TAT, FDP, or D-dimer are increased, the possibility of thrombosis being present is high, and careful imaging tests are required.…”

Editorial Compilation VII

“…This issue begins with several contributions related to the arena of preanalytical variables, or laboratory or potentially point-of-care diagnostics. [9][10][11] The first article provides some guidance around preanalytical variables, which may affect the results of many routine coagulation and also diagnostic hemostasis assays. 12 While advances in laboratory instrumentation have partially addressed the laboratory's ability to recognize some of these variables, there remains increased reliance on laboratory personnel to recognize the three potential areas where coagulation testing preanalytical issues may emerge, these being (1) specimen collection (including patient selection), (2) specimen transportation and stability, and (3) specimen processing and storage.…”

“…10 This issue of STH continues the exploration of laboratory testing with a third contribution, by Ames and colleagues, on coagulation activation markers in antiphospholipid syndrome (APS). 11 In particular, prothrombin fragment F1 þ 2 (F1 þ 2) and thrombin-antithrombin (TAT) have been assessed in APS, but without evaluating a direct relationship with antiphospholipid (aPL) antibody titers. The authors of this hybrid report, comprising a systematic review and metaanalysis combined with a short report of original data, aimed to investigate whether a direct relationship between aPL and F1 þ 2 could be identified, as well as to perform a systematic review and meta-analysis of F1 þ 2 and TAT in APS.…”

“…Thus, F1 þ 2 measurements may be unfounded as already demonstrated for TAT in the 1990s. 11 Continuing the exploration of APS, Tufano et al 15 review its cardiac manifestations, including clinical presentation, role of cardiac imaging, and treatment strategies. As noted earlier, APS is an autoimmune disorder characterized by the presence of aPL, but also vascular thrombosis (venous, arterial, or small vessels) and/or pregnancy morbidity.…”