Properties of procoagulant platelets: Defining and characterizing the subpopulation binding a functional prothrombinase

Ammon M. Fager, Jeremy P. Wood, Beth A. Bouchard, Ping Feng, Paula B. Tracy

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Objective- The goal of this study was to define and characterize the subpopulation of platelets capable of regulating the functional interactions of factors Va (FVa) and Xa (FXa) on the thrombin-activated platelet surface. Methods and Results- Flow cytometric analyses were used to define and characterize platelet subpopulations. At a concentration of thrombin known to elicit maximal platelet activation, platelet-derived FVa release, and prothrombinase assembly/function, only a subpopulation of platelets was positive for FVa and FXa binding. An additional subpopulation bound lower levels of FVa but little, if any, FXa. Fluorescence microscopy analyses confirmed these data. Phenotypically, platelets capable of binding FXa were more highly reticulated and demonstrated significantly increased expression of several key adhesion molecules, including P-selectin, glycoprotein Ibα, and integrins αIIb and β3. This platelet subpopulation was also defined by the expression of a nondissociable, membrane-bound pool of functional platelet-derived FVa, which made up ≥35% to 50% of the total membrane-bound cofactor. Conclusion- The ability of activated platelets to support thrombin generation is defined by a subpopulation of platelets expressing a nondissociable pool of platelet-derived FVa and increased adhesive receptor density. This subpopulation is hypothesized to play a significant role in regulating both normal hemostasis and pathological thrombus formation because the adherent properties of platelets and their ability to mount and sustain a procoagulant response are crucial steps in both of these processes.

Original languageEnglish
Pages (from-to)2400-2407
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume30
Issue number12
DOIs
StatePublished - Dec 2010

Bibliographical note

Funding Information:
It is a pleasure to acknowledge the fruitful collaborations with many students and scientists who appear as co-authors in publications of the authors of this chapter. We gratefully acknowledge financial support from the Deutsche Forschungsgemeinschaft through SFB 583 “Redox-active metal complexes, and the Fonds der Chemischen Industrie.

Keywords

  • adhesion molecules
  • coagulation
  • factor V
  • platelets
  • thrombin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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