Circulating platelet-derived microparticles in systemic lupus erythematosus

Jaime Pereira; Gino Alfaro; Manuela Goycoolea; Teresa Quiroga; Mauricio Ocqueteau; Loreto Massardo; Carol Pérez; Claudia Sáez; Olga Panes; Valeria Matus; Diego Mezzano

doi:10.1160/TH05-05-0310

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(01): 94-99
DOI: 10.1160/TH05-05-0310

Platelets and Blood Cells

Schattauer GmbH

Circulating platelet-derived microparticles in systemic lupus erythematosus

Association with increased thrombin generation and procoagulant state

Jaime Pereira

¹Departments of Hematology-Oncology, Clinical Laboratory and Rheumatology, School of Medicine, Catholic University of Chile, Santiago, Chile

,

Gino Alfaro

¹Departments of Hematology-Oncology, Clinical Laboratory and Rheumatology, School of Medicine, Catholic University of Chile, Santiago, Chile

,

Manuela Goycoolea

¹Departments of Hematology-Oncology, Clinical Laboratory and Rheumatology, School of Medicine, Catholic University of Chile, Santiago, Chile

,

Teresa Quiroga

¹Departments of Hematology-Oncology, Clinical Laboratory and Rheumatology, School of Medicine, Catholic University of Chile, Santiago, Chile

,

Mauricio Ocqueteau

¹Departments of Hematology-Oncology, Clinical Laboratory and Rheumatology, School of Medicine, Catholic University of Chile, Santiago, Chile

,

Loreto Massardo

¹Departments of Hematology-Oncology, Clinical Laboratory and Rheumatology, School of Medicine, Catholic University of Chile, Santiago, Chile

,

Carol Pérez

¹Departments of Hematology-Oncology, Clinical Laboratory and Rheumatology, School of Medicine, Catholic University of Chile, Santiago, Chile

,

Claudia Sáez

¹Departments of Hematology-Oncology, Clinical Laboratory and Rheumatology, School of Medicine, Catholic University of Chile, Santiago, Chile

,

Olga Panes

¹Departments of Hematology-Oncology, Clinical Laboratory and Rheumatology, School of Medicine, Catholic University of Chile, Santiago, Chile

,

Valeria Matus

¹Departments of Hematology-Oncology, Clinical Laboratory and Rheumatology, School of Medicine, Catholic University of Chile, Santiago, Chile

,

Diego Mezzano

¹Departments of Hematology-Oncology, Clinical Laboratory and Rheumatology, School of Medicine, Catholic University of Chile, Santiago, Chile

› Author Affiliations

Abstract

Summary

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 x103/ml plasma, p: 0.0007). In both groups, most of these MP were of platelet origin (927± 131 vs 517 ± 72 x103/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 of TAT in patients and controls were 3.4 ± 0.8 and 1.4 ± 0.5 µg/L, respectively (p:0.04), and of PAP complexes were 62.5 ± 14 and 24.05± 2.5 µg/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.

Keywords

Systemic lupus erythematosus - microparticles - thrombin generation

Full Text

References

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