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Endothelialized Microfluidics for Studying Microvascular Interactions in Hematologic Diseases
Published on: June 22, 2012
Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes
Arun S Shet1, Omer Aras, Kalpna Gupta
1Vascular Biology Center, University of Minnesota Medical School, Minneapolis, USA. shetx001@umn.edu
Abstract:
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. With the use of flow cytometry to enumerate and characterize MPs, we found total MPs to be elevated in crisis (P =.0001) and steady state (P =.02) in subjects with sickle cell disease versus control subjects. These MPs were derived from erythrocytes, platelets, monocytes, and endothelial cells. Erythrocyte-derived MPs were elevated in sickle crisis (P =.0001) and steady state (P =.02) versus control subjects, as were monocyte-derived MPs (P =.0004 and P =.009, respectively). Endothelial and platelet-derived MPs were elevated in sickle crisis versus control subjects. Total TF-positive MPs were elevated in sickle crisis versus steady state (P =.004) and control subjects (P <.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 patients with sickle cell disease versus control subjects and correlated with total MPs and TF-positive MPs (P <.01 for both). These data support the concept that SCD is an inflammatory state with monocyte and endothelial activation and abnormal TF activity.
Insights
Blood microparticles (MPs) are elevated in sickle cell disease (SCD), originating from erythrocytes, platelets, monocytes, and endothelial cells. Tissue factor-positive MPs, linked to coagulation, are also increased, indicating SCD is an inflammatory condition.
Area of Science:
- Hematology
- Vascular Biology
- Coagulation Science
Background:
- Sickle cell disease (SCD) is characterized by red blood cell abnormalities.
- Previous understanding suggested microparticles (MPs) in SCD arise only from erythrocytes and platelets.
- Endothelial cells and monocytes are known to be activated in SCD, expressing tissue factor (TF).
Purpose of the Study:
- To investigate the cellular origins and TF content of MPs in sickle cell disease.
- To determine if TF-positive MPs contribute to the procoagulant state in SCD.
Main Methods:
- Flow cytometry was used to enumerate and characterize MPs.
- MPs were analyzed for cellular origin (erythrocytes, platelets, monocytes, endothelial cells).
- TF expression on MPs was assessed, and TF-positive MPs' procoagulant activity was measured using plasma-clotting time assays.
Main Results:
- Total MPs and erythrocyte-derived MPs were elevated in both sickle crisis and steady state compared to controls.
- Monocyte-derived MPs were elevated in SCD patients versus controls.
- TF-positive MPs, derived from monocytes and endothelial cells, were significantly increased in sickle crisis and correlated with elevated coagulation markers.
Conclusions:
- Sickle cell disease involves elevated levels of MPs from multiple cell types, including erythrocytes, platelets, monocytes, and endothelial cells.
- TF-positive MPs derived from activated monocytes and endothelial cells contribute to the procoagulant activity observed in SCD.
- These findings support the view of SCD as an inflammatory condition with significant endothelial and monocyte activation and abnormal TF activity.

