Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug?

J Thromb Haemost. 2006 Dec;4(12):2593-8. doi: 10.1111/j.1538-7836.2006.02194.x. Epub 2006 Sep 6.


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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Cell Aggregation / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Fibrinolytic Agents / pharmacology*
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Hydroxyurea / pharmacology*
  • Hydroxyurea / therapeutic use
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Myeloproliferative Disorders / drug therapy*
  • Myeloproliferative Disorders / metabolism
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • P-Selectin / metabolism
  • Platelet Adhesiveness / drug effects
  • Reference Values
  • Thromboplastin / metabolism*


  • Fibrinolytic Agents
  • P-Selectin
  • Thromboplastin
  • Hydroxyurea