Treatment and Outcome of Thrombolysis-Related Hemorrhage: A Multicenter Retrospective Study

Abstract

Importance: Treatments for symptomatic intracerebral hemorrhage (sICH) are based on expert opinion, with limited data available on efficacy.

Objective: To better understand the natural history of thrombolysis-related sICH, with a focus on the efficacy of various treatments used.

Design, setting, and participants: Multicenter retrospective study between January 1, 2009, and April 30, 2014, at 10 primary and comprehensive stroke centers across the United States. Participants were all patients with sICH, using the definition by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), which included a parenchymal hematoma type 2 and at least a 4-point increase in the National Institutes of Health Stroke Scale score.

Main outcomes and measures: The primary outcome was in-hospital mortality, and the secondary outcome was hematoma expansion, defined as a 33% increase in the hematoma volume on follow-up imaging.

Results: Of 3894 patients treated with intravenous recombinant tissue plasminogen activator (rtPA) within 4½ hours after symptom onset of ischemic stroke, 128 (3.3%) had sICH. The median time from initiation of rtPA therapy to sICH diagnosis was 470 minutes (range, 30-2572 minutes), and the median time from diagnosis to treatment of sICH was 112 minutes (range, 12-628 minutes). The in-hospital mortality rate was 52.3% (67 of 128), and 26.8% (22 of 82) had hematoma expansion. In the multivariable models, code status change to comfort measures after sICH diagnosis was the sole factor associated with increased in-hospital mortality (odds ratio, 3.6; 95% CI, 1.2-10.6). Severe hypofibrinogenemia (fibrinogen level, <150 mg/dL) was associated with hematoma expansion, occurring in 36.3% (8 of 22) of patients without hematoma expansion vs in 25.0% (15 of 60) of patients with hematoma expansion (P = .01), highlighting a role for cryoprecipitate in reversing rtPA coagulopathy.

Conclusions and relevance: In this study, treatment of postthrombolysis sICH did not significantly reduce the likelihood of in-hospital mortality or hematoma expansion. Shortening the time to diagnosis and treatment may be a key variable in improving outcomes of patients with sICH.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Yaghi reported receiving funding from the Stroke Trials Network (StrokeNet) of the National Institute of Neurological Disorders and Stroke. Dr Liebeskind reported being a consultant for Stryker and Covidien. Dr Willey reported being a consultant for HeartWare Inc. No other disclosures were reported.

Figures

Figure 1. Patient Flowchart

rtPA indicates recombinant tissue plasminogen activator; sICH, symptomatic intracerebral hemorrhage; and SITS-MOST, Safe Implementation of Thrombolysis in Stroke-Monitoring Study.

Figure 2. Patient With Thrombolysis-Related Symptomatic Intracerebral Hemorrhage

Hematoma expansion was noted on follow-up imaging despite treatment with cryoprecipitate.