Proportion of single-chain recombinant tissue plasminogen activator and outcome after stroke

Neurology. 2016 Dec 6;87(23):2416-2426. doi: 10.1212/WNL.0000000000003399. Epub 2016 Nov 4.


Objective: To determine whether the ratio single chain (sc)/(sc + 2 chain [tc]) recombinant tissue plasminogen activator (rtPA) influences outcomes in patients with cerebral ischemia.

Methods: We prospectively included consecutive patients treated with IV rtPA for cerebral ischemia in 13 stroke centers and determined the sc/(sc + tc) ratio in the treatment administered to each patient. We evaluated the outcome with the modified Rankin Scale (mRS) at 3 months (prespecified analysis) and occurrence of epileptic seizures (post hoc analysis). We registered Outcome of Patients Treated by IV Rt-PA for Cerebral Ischaemia According to the Ratio Sc-tPA/Tc-tPA (OPHELIE) under identifier no. NCT01614080.

Results: We recruited 1,004 patients (515 men, median age 75 years, median onset-to-needle time 170 minutes, median NIH Stroke Scale score 10). We found no statistical association between sc/(sc + tc) ratios and handicap (mRS > 1), dependency (mRS > 2), or death at 3 months. Patients with symptomatic intracerebral hemorrhages had lower ratios (median 69% vs 72%, adjusted p = 0.003). The sc/(sc + tc) rtPA ratio did not differ between patients with and without seizures, but patients with early seizures were more likely to have received a sc/(sc + tc) rtPA ratio >80.5% (odds ratio 3.61; 95% confidence interval 1.26-10.34).

Conclusions: The sc/(sc + tc) rtPA ratio does not influence outcomes in patients with cerebral ischemia. The capacity of rtPA to modulate NMDA receptor signaling might be associated with early seizures, but we observed this effect only in patients with a ratio of sc/(sc + tc) rtPA >80.5% in a post hoc analysis.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brain Ischemia / complications
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / mortality
  • Cerebral Hemorrhage / complications
  • Disability Evaluation
  • Female
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / therapeutic use
  • Seizures / complications
  • Severity of Illness Index
  • Stroke / complications
  • Stroke / drug therapy*
  • Stroke / mortality
  • Thrombolytic Therapy*
  • Time-to-Treatment
  • Tissue Plasminogen Activator / chemistry
  • Tissue Plasminogen Activator / therapeutic use*
  • Treatment Outcome


  • Fibrinolytic Agents
  • Recombinant Proteins
  • Tissue Plasminogen Activator

Associated data