PlumX Metrics
Embed PlumX Metrics

Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro–aged or –injured mouse platelets

Blood, ISSN: 0006-4971, Vol: 102, Issue: 12, Page: 4229-4235
2003
  • 153
    Citations
  • 0
    Usage
  • 64
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

Platelet transfusions are a crucial component of support for patients with severe thrombocytopenia. Storage of platelet concentrates, however, is associated with a reduction in platelet posttransfusion recovery and hemostatic function. In this study, we established a model of mitochondrial injury that resembles platelet storage lesion. Mitochondrial injury, provoked by incubation of platelets with carbonyl cyanide m-chlorophenylhydrazone (CCCP), led to reduced posttransfusion recovery in mice, an effect that directly correlated with the duration of treatment. Damaged platelets were characterized by shape change, disruption of membrane asymmetry, surface expression of P-selectin, and profound proteolysis of GPIbα. Using our model, we identified a key role for endogenous metalloproteinase(s) in platelet clearance, as their inhibition markedly improved posttransfusion recovery of both the mitochondria-injured and in vitro-aged mouse platelets. Metalloproteinase inhibition also prevented proteolysis of GPIbα on damaged platelets, thereby improving the hemostatic function of these cells in vivo. We propose that inhibition of metalloproteinase activity during storage could significantly improve the effectiveness of platelet transfusions. Surface expression of GPIbα might be a powerful marker to determine the quality of platelet concentrates, because it reflects metalloproteinase activity in vitro. (Blood. 2003;102: 4229-4235)

Bibliographic Details

Bergmeier, Wolfgang; Burger, Peter C; Piffath, Crystal L; Hoffmeister, Karin M; Hartwig, John H; Nieswandt, Bernhard; Wagner, Denisa D

American Society of Hematology

Biochemistry, Genetics and Molecular Biology; Immunology and Microbiology; Medicine

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know