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Prepublished online as a Blood First Edition Paper on June 12, 2003; DOI 10.1182/blood-2003-03-0693.

Submitted March 5, 2003
Accepted June 2, 2003
Sickle blood contains tissue factor positive microparticles derived from endothelial cells and monocytes
Arun S Shet*, Omer Aras, Kalpna Gupta, Matthew J Hass, Douglas J Rausch, Nabil Saba, Louann Koopmeiners, Nigel S Key, and Robert P Hebbel
Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA; Vascular Biology Center, University of Minnesota Medical School, Minneapolis, MN, USA
Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA
Section of Hematology and Oncology, Hennepin County Medical Center, Minneapolis, MN, USA; Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA
Section of Hematology and Oncology, Hennepin County Medical Center, Minneapolis, MN, USA
* Corresponding author; email: shetx001{at}umn.edu.
Blood microparticles (MPs) in sickle cell disease (SCD) are reportedly derived only from erythrocytes and platelets. Yet in SCD, endothelial cells and monocytes are activated and abnormally express tissue factor (TF). Thus, sickle blood might contain TF positive MPs derived from these cells. Using flow cytometry to enumerate and characterize MPs, we found total MPs to be elevated in crisis (p=0.0001) and steady state (p=0.02) sickle subjects versus controls. These MPs were derived from erythrocytes, platelets, monocytes, and endothelial cells. Erythrocyte-derived MPs were elevated in sickle crisis (p=0.0001) and steady state (p=0.02) versus controls, as were monocyte-derived MPs (p=0.0004 and p=0.009, respectively). Endothelial and platelet-derived MPs were elevated in sickle crisis versus controls. Total TF positive MPs were elevated in sickle crisis versus steady state (p=0.004)and controls (p<0.0001) and were derived from both monocytes and endothelial cells. Sickle MPs shortened plasma-clotting time compared with control MPs, and a TF antibody partially inhibited this procoagulant activity. Markers of coagulation were elevated in sickle patients versus controls and correlated with total MPs and TF positive MPs (p<0.01 for both). These data support the concept that SCD is an inflammatory state with monocyte and endothelial activation and abnormal TF activity.

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