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 15-72 years, mean age 38 years) and 20 healthy controls (aged 22-54 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 annexin V. 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 x 10(3)/ml plasma, p: 0.0007). In both groups, most of these MP were of platelet origin (927 +/- 131 vs 517 +/- 72 x 10(3)/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 microg/L, respectively (p:0.04), and of PAP complexes were 62.5 +/- 14 and 24.05 +/- 2.5 microg/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.
Pereira
Jaime
J
Department of Hematology-Oncology, Catholic University of Chile, Santiago, Chile. jpereira@med.puc.cl
Alfaro
Gino
G
Goycoolea
Manuela
M
Quiroga
Teresa
T
Ocqueteau
Mauricio
M
Massardo
Loreto
L
Pérez
Carol
C
Sáez
Claudia
C
Panes
Olga
O
Matus
Valeria
V
Mezzano
Diego
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000990:Antithrombin III; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood; D010976:Platelet Count; D013917:Thrombin / Q000378:metabolism*; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; C037742:plasmin-plasmin inhibitor complex; D000990:Antithrombin III; D010447:Peptide Hydrolases; D013917:Thrombin; D005341:Fibrinolysin