Risk factors are different for deep and lobar remote hemorrhages after intravenous thrombolysis

PLoS One. 2017 Jun 22;12(6):e0178284. doi: 10.1371/journal.pone.0178284. eCollection 2017.


Background and purpose: Remote parenchymal haemorrhage (rPH) after intravenous thrombolysis is defined as hemorrhages that appear in brain regions without visible ischemic damage, remote from the area of ischemia causing the initial stroke symptom. The pathophysiology of rPH is not clear and may be explained by different underlying mechanisms. We hypothesized that rPH may have different risk factors according to the bleeding location. We report the variables that we found associated with deep and lobar rPH after intravenous thrombolysis.

Methods: This is a descriptive study of patients with ischemic stroke who were treated with intravenous thrombolysis. These patients were included in a multicenter prospective registry. We collected demographic, clinical and radiological data. We evaluated the number and distribution of cerebral microbleeds (CMB) from Magnetic Resonance Imaging. We excluded patients treated endovascularly, patients with parenchymal hemorrhage without concomitant rPH and stroke mimics. We compared the variables from patients with deep or lobar rPH with those with no intracranial hemorrhage.

Results: We studied 934 patients (mean age 73.9±12.6 years) and 52.8% were men. We observed rPH in 34 patients (3.6%); 9 (0.9%) were deep and 25 (2.7%) lobar. No hemorrhage was observed in 900 (96.6%) patients. Deep rPH were associated with hypertensive episodes within first 24 hours after intravenous thrombolysis (77.7% vs 23.3%, p<0.001). Lobar rPH were associated with the presence of CMB (53.8% vs 7.9%, p<0.001), multiple (>1) CMB (30.7% vs 4.4%, p = 0.003), lobar CMB (53.8% vs 3.0%, p<0.001) and severe leukoaraiosis (76.9% vs 42%, p = 0.02).

Conclusions: A high blood pressure within the first 24 hours after intravenous thrombolysis is associated with deep rPH, whereas lobar rPH are associated with imaging markers of amyloid deposition. Thus, our results suggest that deep and lobar rPH after intravenous thrombolysis may have different mechanisms.

MeSH terms

  • Aged
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / etiology*
  • Female
  • Humans
  • Hypertension / complications
  • Magnetic Resonance Imaging
  • Male
  • Retrospective Studies
  • Risk Factors
  • Stroke / therapy
  • Thrombolytic Therapy / adverse effects*

Grant support

This work was supported by Ministery of Health-Instituto de Salud Carlos III: RETICS (Redes temáticas de Investigación Cooperativa) INVICTUS RD012/0014, FEDER (Fondo Europeo de Desarrollo Regional). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.