CLINICAL RESEARCH: ENDOTHELIAL FUNCTION
Elevation of Endothelial Microparticles, Platelets, and Leukocyte Activation in Patients With Venous Thromboembolism
Julio A. Chirinos, MD*, ,*,
Gustavo A. Heresi, MD*,
Hermes Velasquez, MD*,
Wenche Jy, PhD*,,
Joaquin J. Jimenez, MD*,,
Eugene Ahn, MD*,,
Lawrence L. Horstman, BS*,,
Andres O. Soriano, MD*,
Juan P. Zambrano, MD* and
Yeon S. Ahn, MD*,
* Department of Medicine, University of Miami, Miami, Florida
Wallace H. Coulter Platelet Laboratory, University of Miami, Miami, Florida
Manuscript received September 9, 2004;
revised manuscript received November 11, 2004,
accepted December 20, 2004.
* Reprint requests and correspondence: Dr. Julio A. Chirinos, 7601 East Treasure Drive, 709, Miami, Florida 33141. (Email: jchirinos{at}med.miami.edu).
OBJECTIVES: The purpose of this research was to determine the levels of platelet, leukocyte, and endothelial activation and markers of cellular interactions in patients with venous thromboembolism (VTE).
BACKGROUND: The details of interactions between endothelium, platelets, and leukocytes in VTE are not well understood.
METHODS: We studied 25 patients with VTE and compared 25 healthy controls. We used flow cytometry to measure: 1) endothelial microparticles (EMP) identified by CD31+/CD42b– (EMP31) or E-selectin (EMP62E); 2) platelet microparticles (CD31+/CD42b+); 3) surface expression of P-selectin in platelets and CD11b in leukocytes; 4) EMP-monocyte conjugates (percentage of monocytes positive for E-selectin); and 5) platelet-leukocyte conjugates (PLC) expressed as percentage of leukocytes positive for CD41.
RESULTS: Patients with VTE had marked elevations of EMP31 (2,193 vs. 383 counts/µl; p = 0.003), EMP62E (368 vs. 223 counts/µl; p = 0.001), and EMP-monocyte conjugates (3.3% vs. 2.5%; p = 0.002), as well as increased activation of platelets (35.2 vs. 5.0 fluorescence intensity units for P-selectin; p < 0.0001) and leukocytes (13.9 vs. 7.7 U for CD11b; p = 0.004). Also elevated in VTE were PLC (61.7% vs. 39.6%; p = 0.01). Expression of CD11b in leukocytes strongly correlated with PLC (r = 0.74; p < 0.0001).
CONCLUSIONS: Marked activation of endothelium, platelets, and leukocytes occurs in VTE, and VTE, or the accompanying inflammatory process, involves the release of EMP and formation of EMP-monocyte conjugates and PLC. These findings support prior studies suggesting that release of EMP and their binding to monocytes are key events in thrombogenesis. Our findings also support the concept that the formation of PLC regulates leukocyte activation and participates in linking thrombosis with inflammation.
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Abbreviations and Acronyms
| | DVT = deep vein thrombosis | | EC = endothelial cell | | EMP = endothelial microparticles | | IQR = interquartile range | | mAb = monoclonal antibodies | | PE = pulmonary embolism | | PMP = platelet microparticles | | TF = tissue factor | | VTE = venous thromboembolism |
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