Plasma microparticle tissue factor activity in patients with antiphospholipid antibodies with and without clinical complications

Abstract

Antiphospholipid syndrome (APS) is defined by the association of autoantibodies to certain phospholipid-binding proteins with arterial or venous thrombosis ('AT' or 'VT', respectively), and/or pregnancy-related morbidity (PM). Antiphospholipid antibodies (aPLA) promote activation of several cell types including monocytes, resulting in procoagulant tissue factor (TF) expression that may contribute to the vascular complications. Since TF synthesis by monocytes is frequently accompanied by release of TF-bearing microparticles, we hypothesized that plasma microparticle TF activity (MP-TF) may be elevated in APS patients and contribute to thrombosis and/or PM. Platelet-poor plasma specimens were obtained from 30 patients with definite APS and 72 patients with asymptomatic aPLA from the Antiphospholipid Syndrome Collaborative Registry (APSCORE). MP-TF was measured by an in-house factor Xa generation assay. The two groups were well matched for gender, age, ethnicity, proportions with underlying SLE, and aPLA profiles. MP-TF (median and (IQR)) in asymptomatic aPLA subjects was 0.09 pg/mL (0.05-0.14) compared to 0.13 pg/mL (0.10-0.17) in APS (p < 0.001). No differences in MP-TF levels were observed between APS subjects with PM, thrombosis, or PM+thrombosis. Similarly, among subjects with either APS or asymptomatic aPLA, MP-TF did not differ in the presence or absence of underlying SLE. Prospective studies will be required to determine if plasma MP-TF activity is causally related to thrombotic or gestational complications in APS.

Keywords: Antiphospholipid syndrome; Microparticle; Pregnancy; Thrombosis; Tissue factor.

Figure 1

Figure 1A: MP-TF activity in subjects with anti-phospholipid syndrome (APS) and control subjects with asymptomatic anti-phospholipid antibodies (APL). Data are presented as medians and inter-quartile ranges. [***p<0.001]. Figure 1B: MP-TF activity according to sub-groups. Data are presented as medians and inter-quartile ranges. Abbreviations: Th = history of thrombosis; PM = history of pregnancy-related morbidity; aPL (−) = asymptomatic with antiphospholipid antibodies but without SLE; aPL (+) = asymptomatic with antiphospholipid antibodies and SLE.