Loss of Platelet Membrane Phospholipid Asymmetry in Systemic Lupus Erythematosus: Association with Disease Activity and Hypercoagulable State.

Accelerated atherosclerosis (AE) not being explained by traditional risk factors, occurs frequently in systemic lupus erythematosus (SLE). Both SLE and AE share the condition of chronic inflammatory processes. Circulating, activated platelets, present in SLE patients, have been shown to exacerbate and promote AE in an animal model. Activated and/or apoptotic platelets lose membrane phopholipid asymmetry and expose negatively charged phosphatidylserine (PS), events that promote thrombin generation. In this context, it is well known that SLE serum has a strong apoptosis-inducing capacity on circulating blood cells. The aim of this work was to study the occurrence of apoptotic-like changes (PS exposure and loss of mitochondrial membrane potential [Δψ]) in circulating platelets in SLE patients and their relationship with an hipercoagulable state. Thirty patients with SLE (aged 15–72 years, mean age 38 years) and 30 healthy controls (aged 20–65 years, mean age 40 years) were studied. Patients fulfilled 4 revised criteria for SLE and disease activity was assessed by a modified SLE Disease Activity Index (MexSLEDAI). PS exposure was determined by flow cytometry (FC) by double labeling with FITC-labeled annexin V and PE-labeled anti-CD-61. The Δψ was studied with the J-aggregate-forming cation JC-1 and analyzed by FC. Tissue factor-dependent platelet procoagulant activity (pPCA) was determined in platelet membranes by conversion of factor X to Xa in the presence of FVIIa. Circulating microparticles were quantified through its PCA after being captured on a microtiter plate by annexin V and expressed as nM of PS. Soluble tissue factor (sTF) and thrombin anti-thrombin complexes (TAT) were measured by ELISA (American Diagnostica). The results are shown in the table:

The results confirm a hypercoagulable state in SLE demonstrated by increased levels of TAT and sTF. PS exposure was significantly higher in active SLE patients than in healthy controls and decrease in mitochondrial Δψ suggests that apoptosis plays a role in this phenomenon. Our data also indicate that PS exposure in SLE platelets is associated with increased procoagulant activity of these cells and with higher levels of circulating MP. Moreover, PS exposure was positively correlated with levels of TAT (r: 0.55; p: 0.022; n:16). Taken together, our results suggest that loss of platelet membrane phospholipid asymmetry with PS externalization may constitute an important mechanism in the pathogenesis of the hypercoagulable state observed in SLE.