Platelet apoptosis and agonist-mediated activation in myelodysplastic syndromes

Thromb Haemost. 2013 May;109(5):909-19. doi: 10.1160/TH12-09-0670. Epub 2013 Feb 14.

Abstract

Patients with myelodysplastic syndromes (MDS) have a defect in the differentiation of bone marrow multipotent progenitor cells. Thrombocytopenia in MDS patients may be due to premature megakaryocyte death, but platelet apoptotic mechanisms may also occur. This study aimed to study function and apoptotic state of platelets from MDS patients with different platelet count. Reticulated platelets, platelet activation, activated caspases and annexin-V binding were evaluated by flow cytometry. Pro-apoptotic Bax and Bak proteins were determined by western blots and plasma thrombopoietin by ELISA. Microparticle-associated procoagulant activity and thrombin generation capacity of plasma were determined by an activity kit and calibrated automated thrombography, respectively. High plasma thrombopoietin levels and low immature circulating platelet count showed a pattern of hypoplastic thrombocytopenia in MDS patients. Platelets from MDS patients showed reduced activation capacity and more apoptosis signs than controls. Patients with the lowest platelet count showed less platelet activation and the highest extent of platelet apoptosis. On this basis, patients with thrombocytopenia should suffer more haemorrhagic episodes than is actually observed. Consequently, we tested whether there were some compensatory mechanisms to counteract their expected bleeding tendency. Microparticle-associated procoagulant activity was enhanced in MDS patients with thrombocytopenia, whereas their plasma thrombin generation capacity was similar to control group. This research shows a hypoplastic thrombocytopenia that platelets from MDS patients possess an impaired ability to be stimulated and more apoptosis markers than those from healthy controls, indicating that MDS is a stem cell disorder, and then, both number and function of progeny cells, might be affected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Annexin A5 / blood
  • Apoptosis*
  • Blood Coagulation
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Blood Platelets / pathology
  • Blotting, Western
  • Case-Control Studies
  • Caspases / blood
  • Cell-Derived Microparticles / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / blood*
  • Myelodysplastic Syndromes / pathology
  • Peptide Fragments / pharmacology*
  • Platelet Activation / drug effects*
  • Platelet Count
  • Thrombelastography
  • Thrombin / metabolism
  • Thrombocytopenia / blood*
  • Thrombocytopenia / pathology
  • Thrombopoietin / blood
  • Young Adult
  • bcl-2 Homologous Antagonist-Killer Protein / blood
  • bcl-2-Associated X Protein / blood

Substances

  • Annexin A5
  • BAK1 protein, human
  • BAX protein, human
  • Peptide Fragments
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • thrombin receptor peptide (42-47)
  • Adenosine Diphosphate
  • Thrombopoietin
  • Thrombin
  • Caspases