Genes involved in hemorrhagic transformations that follow recombinant t-PA treatment in stroke patients

Pharmacogenomics. 2013 Apr;14(5):495-504. doi: 10.2217/pgs.13.19.


Aim: Despite the benefits of recombinant t-PA (rt-PA) for stroke patients some of them suffer from adverse hemorrhagic transformations (HTs) following treatment. Our objective is to study the transcriptomics of HTs patients.

Methods: We studied by microarrays 11 blood samples from patients with stroke that had received rt-PA of whom six of them had suffered a HT. For replication step RNA was collected from 14 new subjects (seven with HT, seven without) and then analyzed by real-time PCR. Four proteins were measured by ELISA in 72 new subjects to analyze their role as potential protein biomarkers.

Results: The microarray analysis revealed that 14 genes were altered among the HT patients. The replication study confirmed these results for six genes. Two of them (BCL2 and OLFM4) are associated with apoptosis, whereas the other four (LTF, LCN2 [also known as NGAL], CEACAM8 and CRISP3) are involved in the regulation of neutrophil processes.

Conclusion: Our data revealed that genes related to apoptosis and neutrophil regulation pathways could be associated with HTs after rt-PA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Drug-Related Side Effects and Adverse Reactions / genetics*
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Gene Regulatory Networks
  • Hemorrhage / chemically induced*
  • Hemorrhage / complications
  • Hemorrhage / genetics*
  • Hemorrhage / pathology
  • Humans
  • Male
  • Neutrophils / metabolism
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Stroke / complications
  • Stroke / drug therapy
  • Stroke / genetics*
  • Stroke / pathology
  • Tissue Plasminogen Activator / administration & dosage
  • Tissue Plasminogen Activator / adverse effects
  • Treatment Outcome


  • Recombinant Proteins
  • Tissue Plasminogen Activator