Related Experiment Video
Updated: Jul 20, 2026
Flow Cytometry Analysis of Tissue Factor Expression in Human Platelets
Published on: November 22, 2024
Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with
N Maugeri1, G Giordano, M P Petrilli
1Laboratory of Cell Biology and Pharmacology of Thrombosis, Research Laboratories, Catholic University, Campobasso, Italy. normamaugeri2003@yahoo.it
Background:
Polymorphonuclear leukocytes (PMN) from healthy subjects can produce and store tissue factor (TF), which is expressed on PMN surface upon in vitro stimulation with P-selectin.
Results:
We report here that platelets and PMN from 12 patients with myeloproliferative disorders (MPD) (six with polycythemia vera, six with essential thrombocythemia) show up regulation of P-selectin and TF, respectively, in the absence of any in vitro challenge. The number of circulating mixed platelet-PMN aggregates was also increased. PMN TF expression as well as mixed platelet-PMN aggregates, but not platelet P-selectin, were significantly reduced in six MPD patients after treatment with hydroxyurea (HU). In vitro studies performed on PMN separated from healthy donors confirmed HU effects (0-1400 microm). HU prevented both P-selectin-induced TF expression and mixed cell aggregate formation. The inhibitory effect of HU was specific for P-selectin-induced PMN activation, as it did not affect formyl-methionyl-leucyl-phenylalanine-induced PMN TF expression.
Conclusions:
In MPD patients, platelet P-selectin-mediated TF expression on circulating PMN may play a role in thrombus formation and represents a novel target for the antithrombotic activity of HU.
Insights
Platelets and neutrophils in myeloproliferative disorders (MPD) show increased P-selectin and tissue factor (TF). Hydroxyurea (HU) treatment reduced these markers and platelet-PMN aggregates, suggesting HU
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Polymorphonuclear leukocytes (PMN) produce tissue factor (TF), expressed upon P-selectin stimulation.
- P-selectin and TF are upregulated on platelets and PMN in myeloproliferative disorders (MPD).
Purpose of the Study:
- To investigate the role of P-selectin and TF in MPD.
- To evaluate the effect of hydroxyurea (HU) on platelet-PMN interactions in MPD.
Main Methods:
- Analysis of P-selectin and TF expression on PMN and platelets in MPD patients.
- Assessment of circulating platelet-PMN aggregates.
- In vitro studies on PMN from healthy donors treated with HU.
Main Results:
- MPD patients exhibit elevated P-selectin and TF, and increased platelet-PMN aggregates.
- Hydroxyurea (HU) treatment significantly reduced PMN TF expression and platelet-PMN aggregates in MPD patients.
- In vitro, HU inhibited P-selectin-induced TF expression and aggregate formation in a dose-dependent manner.
Conclusions:
- Platelet P-selectin-mediated TF expression on PMN contributes to thrombus formation in MPD.
- HU demonstrates antithrombotic activity by targeting this pathway.
- This pathway represents a novel therapeutic target for MPD.
Related Concept Videos
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:28Role of Hematopoietic Growth Factors
Thrombopoietin (TPO), mainly released by the liver,...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase