Changes to fibrinolysis in patients with systemic lupus erythematosus are associated with endothelial cell damage and inflammation, but not antiphospholipid antibodies.

We investigated whether changes to fibrinolysis were associated with other manifestations of systemic lupus erythematosus (SLE), including antiphospholipid (APL) antibody status, endothelial damage, and inflammation. Ninety-four patients (36 SLE patients, 58 healthy controls) were recruited from Tasmania, Australia. Circulating levels of plasminogen, α2-antiplasmin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured, as well as APL antibodies (including lupus anticoagulant, anticardiolipin, and antibeta-2 glycoprotein-1 antibodies), soluble E-selectin, and interleukin-6. Whereas there was a significant decrease in plasminogen (patient vs. control; median) (210 vs. 444 ng/ml; P < 0.0001) and increase in α2-antiplasmin (0.53 vs. 0.09 µg/ml; P = 0.0007), there was increased t-PA (0.65 vs. 0.40 ng/ml; P = 0.0001) and decreased TAFI (8.8 vs. 10.0 ng/ml; P = 0.002) in SLE patients compared to healthy controls. Plasminogen was significantly associated with α2-antiplasmin (rho = -0.563, P < 0.001); TAFI (rho = 0.410, P = 0.011); soluble E-selectin (rho = 0.531, P = 0.001); and interleukin-6 (rho = 0.489, P = 0.002) in SLE patients; however, APL antibody status was not associated with any of the markers measured. This study has demonstrated that fibrinolysis is significantly altered in patients with SLE compared to controls, and associated with endothelial cell damage and inflammation, but not APL antibody status.

Thrombosis in systemic lupus erythematosus: role of impaired fibrinolysis.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can affect any part of the body, including the skin, liver, kidneys, and blood. Thrombosis is a frequent manifestation in SLE, contributing significantly to patient morbidity and mortality, although the precise mechanism(s) of how this occurs remains unclear. Fibrinolysis is the physiologic process of thrombus digestion and provides an important balance to hemostasis. This process is triggered upon vessel injury with the release of tissue-type plasminogen activator (t-PA) from endothelial cells. The central component of the fibrinolytic pathway is plasminogen, a zymogen that is converted to plasmin by t-PA. Plasminogen/plasmin is absorbed into the developing thrombus and digests fibrinogen and fibrin within the hemostatic plug to prevent excessive clot formation. Abnormalities of the fibrinolytic pathway are associated either with the development of thrombosis (impaired fibrinolysis) or, to a lesser extent, bleeding (excessive fibrinolysis). Indeed, impaired fibrinolysis has been reported in patients with SLE and may contribute to both the development of hypercoagulability and an increased risk of thrombosis. Here we discuss the role of impaired fibrinolysis and its contribution to hypercoagulability and thrombosis in SLE.