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Jaime Pereira, Gino Alfaro, Manuela Goycoolea, Teresa Quiroga, Mauricio Ocqueteau, Loreto Massardo, Carol Prez, Claudia Sez, Olga Panes, Valeria Matus, Diego Mezzano

Circulating platelet-derived microparticles in systemic lupus erythematosus. Association with increased thrombin generation and procoagulant state

The risk for thrombosis is significantly increased in systemic lupus erythematosus (SLE), affecting both venous and arterial vessels. Activated platelets are known to participate in thrombus formation and growth. A general feature of activated cells is the shedding of microparticles (MP) which support coagulation by exposure of negatively charged phospholipids and possibly tissue factor (TF). In this work we characterized circulating MP in patients with SLE and their relationship with a procoagulant state. Thirty patients with SLE (aged 1572 years, mean age 38 years) and 20 healthy controls (aged 2254 years, mean age 34 years) were studied; patients fulfilled 4 revised criteria for SLE. The number and cellular source of circulating MP were determined by flow cytometry using double labeling with specific monoclonal antibodies and annexinV. Thrombin generation was measured as the endogenous thrombin potential (ETP) without the addition of exogenous phospholipids and TF; under these conditions the generation of thrombin depended directly on the number of MP present in plasma. Thrombin anti-thrombin (TAT) and plasmin-antiplasmin (PAP) complexes were measured by ELISA. Compared to the controls, circulating MP were significantly elevated in the patient group (1218 136 vs 653 74 103/ml plasma, p: 0.0007). In both groups, most of these MP were of platelet origin (927 131 vs 517 72 103/ml plasma, p:0.009 ). ETP was higher among patients as compared to the controls (804 64 vs 631 37 nM thrombin, p: 0.025). Plasma levels ofTAT in patients and controls were 3.4 0.8 and 1.4 0.5 g/L, respectively (p:0.04), and of PAP complexes were 62.5 14 and 24.05 2.5 g/ml, respectively (p: 0.014). The number of platelet-derived MP correlated significantly with thrombin generation (r: 0.42; p: 0.038) and TAT levels (r: 0.40; p: 0.035). We did not find an association of circulating MP with disease activity nor with the presence of antiphospholipid antibodies. The increased number of circulating platelet-derived microparticles and their association with high ETP and activation of the coagulation system suggest that these microparticles play an important role in the pathogenesis of the prothrombotic state in SLE patients.

Thrombosis and Haemostasis, Schattauer

Print ISSN: 0340-6245
Volume: 95, 01/2006
Pages: 94 - 99

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