The inflammation and coagulation cross-talk in patients with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder with a high prevalence of cardiovascular disease due to accelerated atherosclerosis, as well as an increased risk of venous thromboembolism. Many of these clinical features have been attributed to the high prevalence of autoantibodies that are directed against phospholipid-bound antigens and that induce prothrombotic effects and disturb endothelial cell function. We conducted a case-control study in a cohort of female patients with SLE and in age-matched and sex-matched normal individuals. Patients had significantly higher levels of plasma inflammatory markers, but their overall coagulation status assessed by prothrombin fragment 1 + 2 and D-dimer plasma levels was not different from controls. Resistance against activated protein C (APC), assessed by a thrombin generation-based as well as an activated partial thromboplastin time-based method, however, was increased in patients. This defect was neither due to factor V Leiden carriership or to the use of oral contraceptives. This acquired form of APC resistance was due to proinflammatory changes associated with lower plasma levels of free protein S. In conclusion, acquired APC resistance may be an important determinant of the risk of thrombosis in patients with SLE, probably due to an active cross-talk between inflammation and coagulation systems.

Combined oral contraceptive use and the risk of systemic lupus erythematosus

“…Both could be associated with the underlying inflammatory and autoimmune susceptibility without being specifically associated with SLE diagnosis criteria, as reported previously (33)(34)(35)(36)(37). Adjustment for these factors slightly decreased the RR as compared with the crude RR, but the results remained significant.…”

Characterization of the thrombin generation profile in systemic lupus erythematosus

“…These studies indicate that in the presence of aPL antibodies, the hypercoagulable state is characterized by activated protein C (aPC) resistance (6,13,14,19,22) and they also suggest the involvement of microparticles (17). However, the results are inconsistent, probably, due to differences in the applied TG assays.…”

“…Since TG can reliably reflect the general thrombotic or bleeding tendency (10), several studies applied TG assays for the exploration of the effects of different factors on hemostasis (1,19) as well as for the investigation of the pathogenesis of the prothrombotic state in SLE (6,13,14,17,19,22). These studies indicate that in the presence of aPL antibodies, the hypercoagulable state is characterized by activated protein C (aPC) resistance (6,13,14,19,22) and they also suggest the involvement of microparticles (17).…”

Immunobiology of the TAM receptors

“…On the flip side, diminished or interrupted TAM receptor signalling may lead to the development of chronic inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. This clearly happens in TAM-deficient mice 21,25 ; and in humans, reduced levels of free circulating protein S, which should result in reduced TAM receptor signalling, are evident in patients with SLE [86][87][88] . Therefore, the analysis of TAM receptor signalling is likely to have an increasingly prominent role in our understanding of both the normal innate immune response and its perturbation in disease.…”