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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4545-4553.
Prepublished online as a Blood First Edition Paper on February 26, 2004; DOI 10.1182/blood-2003-03-0713.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Induction of microparticle- and cell-associated intravascular tissue factor in human endotoxemia
Omer Aras,
Arun Shet,
Ronald R. Bach,
Jessica L. Hysjulien,
Arne Slungaard,
Robert P. Hebbel,
Gines Escolar,
Bernd Jilma, and
Nigel S. Key
From the Departments of Medicine (Hematology, Oncology and Transplantation) and the Vascular Biology Center, University of Minnesota, and the Research Service, Minneapolis VA Medical Center, Minnesota; the Servicio de Hemoterapia-Hemostasia, Hospital Clinic, University of Barcelona, Spain; and the Department of Clinical Pharmacology, Vienna University, Austria.
The precise role of intravascular tissue factor (TF) remains poorly defined, due to the limited availability of assays capable of measuring circulating TF procoagulant activity (PCA). As a model of inflammation-associated intravascular thrombin generation, we studied 18 volunteers receiving an infusion of endotoxin. A novel assay that measures microparticle (MP)-associated TF PCA from a number of cellular sources (but not platelets) demonstrated an 8-fold increase in activity at 3 to 4 hours after endotoxin administration (P < .001), with a return to baseline by 8 hours. TF antigen-positive MPs isolated from plasma were visualized by electron microscopy. Interindividual MP-associated TF response to lipopolysaccharide (LPS) was highly variable. In contrast, a previously described assay that measurestotal (cell and MP-borne) whole-blood TF PCA demonstrated a more modest increase, with a peak in activity (1.3-fold over baseline; P < .000 01) at 3 to 4 hours, and persistence for more than 24 hours. This surprisingly modest increase in whole-blood TF activity is likely explained by a profound although transient LPS-induced monocytopenia. MP-associated TF PCA was highly correlated with whole-blood TF PCA and total number of circulating MPs, and whole-blood TF PCA was highly correlated with TF mRNA levels. (Blood. 2004;103:4545-4553)
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