Increased thrombin generation and activity in patients with systemic lupus erythematosus and anticardiolipin antibodies: evidence for a prothrombotic state [see comments]

Abstract

The objective of this study is to determine whether patients with systemic lupus erythematosus (SLE) and anticardiolipin antibodies (ACA) have biochemical evidence of an ongoing prothrombotic state. Using a cross-sectional analysis of a cohort design in an outpatient SLE clinic setting, 43 consecutive patients with SLE participated. Patients underwent clinical and laboratory evaluations on two separate occasions at least 3 months apart. As part of the clinical evaluation, the following were ascertained: (1) the ongoing use of warfarin therapy; (2) the presence of prior venous and arterial thromboembolic disease by history, critical review of objective tests, and examination for reflux in the deep veins of the legs as an indicator of venous thrombosis; and (3) disease-related activity by performing a lupus activity criteria count (LACC). As part of the laboratory evaluation, blood was taken on both occasions and assayed for prothrombin fragments (F1 + 2) and fibrinopeptide A (FPA), as indices of thrombin generation and activity, respectively, and ACA. For the analyses, patients were classified as ACA+ if the assay was abnormal on both occasions and ACA- if the assay was negative on both occasions or negative on one occasion and positive on the other. ACA+ patients had: (1) a significantly higher mean level of F1 + 2 (1.07 nmol/L) than ACA- patients (0.79 nmol/L; P = .02) and patients receiving warfarin (0.47 nmol/L; P = .009) and (2) a significantly higher mean level of FPA (1.01 nmol/L) than ACA- patients (0.45 nmol/L; P = .02). When patients with prior thromboembolism were excluded from the analysis, significant differences in the mean levels of F1 + 2 and FPA between ACA+ and ACA- patients were still seen, whereas when patients with prior thromboembolism and/or active disease were excluded from the analysis, a significant difference in the mean level of FPA and a nonsignificant trend in the mean level of F1 + 2 were seen. The results of this study support the hypothesis that the presence of ACA in SLE patients is associated with an ongoing prothrombotic state.

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

“…After completion of the screening process (►Fig. 1), 18 studies met the criteria for inclusion in the systematic review and meta-analysis: 6 studies investigated both F1 þ 2 and TAT, 3,12-16 7 studies investigated F1 þ 2 only, [17][18][19][20][21][22][23] and 4 investigated TAT only. [24][25][26][27] One of the studies 27 did not report the number of patients positive and negative for aPL, and at the time of submission of this article the authors had not replied to our request for such numbers.…”

“…Stimulated by this inconsistency, we performed our systematic review to verify how many groups had evaluated a direct relationship between aPL and coagulation activation markers and we then performed a meta-analysis on the available data. With regard to the systematic review, only two articles described aPL mean, 17,25 one aPL range, 21 and one mean LA ratio, 25 whereas the remaining articles reported only the positive or negative aPL status to categorize patient groups; none of the authors attempted a direct correlation of aPL with F1 þ 2 and/or TAT. With regard to the meta-analysis, the majority of the studies included dealt with SLE.…”

“…1 used in one study. 18 We calculated average F1 þ 2 in thrombotic and nonthrombotic SLE patients from the studies of Ginsberg et al 17 and Ferro et al 20 according to their published ►Table 1.…”

Can pregnancy induce relapse in systemic lupus erythematosus (SLE)?

“…No significant association between other clinical findings and fetal wastage was detected. Previous studies have introduced other predictive factors for fetal loss such as preconceptional active lupus nephritis, history of fetal loss, and high antiphosphopholipid antibody titers [30][31][32][33][34][35][36].…”

Antiphospholipid Antibodies and Platelets

“…3 The association of thrombosis is stronger with persistent than with transient APA. In addition, Ginsberg et al 29 showed that SLE patients with ACA had significantly higher plasma fibrinopeptide A and prothrombin fragments (F1+2) levels than ACA-negative patients. The association between APA and thrombosis extends beyond the setting of SLE to other autoimmune diseases.…”