Remote Intracerebral Hemorrhage After Intravenous Thrombolysis

Abstract

Background and Purpose— Remote parenchymal hemorrhage (rPH) after intravenous thrombolysis with recombinant tissue-type plasminogen activator may be associated with cerebral amyloid angiopathy, although supportive data are limited. We aimed to investigate risk factors of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator. Methods— This is an observational study of patients with ischemic stroke who were treated with intravenous thrombolysis with recombinant tissue-type plasminogen activator and were included in a multicenter prospective registry. rPH was defined as any extraischemic hemorrhage detected in the follow-up computed tomography. We collected demographic, clinical, laboratory, radiological, and outcome variables. In the subset of patients who underwent a magnetic resonance imaging examination, we evaluated the distribution and burden of cerebral microbleeds, cortical superficial siderosis, leukoaraiosis, and recent silent ischemia in regions anatomically unrelated to the ischemic lesion that caused the initial symptoms. We compared patients with rPH with those without rPH or parenchymal hemorrhage. Independent risk factors for rPH were obtained by multivariable logistic regression analyses. Results— We evaluated 992 patients (mean age, 74.0±12.6 years; 52.9% were men), and 408 (41%) of them underwent a magnetic resonance imaging. Twenty-six patients (2.6%) had a rPH, 8 (0.8%) had both rPH and PH, 58 (5.8%) had PH, and 900 (90.7%) had no bleeding complication. Lobar cerebral microbleeds (odds ratio, 8.0; 95% confidence interval, 2.3–27.2) and recent silent ischemia (odds ratio, 4.8; 95% confidence interval, 1.6–14.1) increased the risk of rPH. Conclusions— The occurrence of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator in patients with ischemic stroke is associated with lobar cerebral microbleeds and multiple ischemic lesions in different regions.

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

“…There is increasing evidence of a link between CAA and ICH after IV-rtPA [2,11,12]. A large meta-analysis [11] of patients with ischemic stroke who were treated with IV-rtPA showed that patients who exhibited CMB and had a high burden of CMB were associated with a high risk symptomatic ICH.…”

“…However, in these studies [11,12] a separate analysis of rPH was not reported. Recently, a multicenter study [2] showed that lobar CMB were associated with rPH. In addition, rPH after IV-rtPA has been documented to occur at a site of CMB [13].…”

“…Remote parenchymal hemorrhage (rPH) is defined as single or multiple hemorrhages that appear in brain regions without visible ischemic damage detected by cranial computed tomography (CT), remote from the area of ischemic causing the initial symptom [2]. This type of ICH occurs in 1.3–3.7% of patients within 24–36 hours after the infusion of IV-rtPA but risk factors are not well-known [2–4].…”

“…This type of ICH occurs in 1.3–3.7% of patients within 24–36 hours after the infusion of IV-rtPA but risk factors are not well-known [2–4]. It is likely that IV-rtPA triggers rPH when there is an underlying hemorrhagic-prone cerebral angiopathy, such as hypertensive and amyloid angiopathies [2,4,5].…”

“…This type of ICH occurs in 1.3–3.7% of patients within 24–36 hours after the infusion of IV-rtPA but risk factors are not well-known [2–4]. It is likely that IV-rtPA triggers rPH when there is an underlying hemorrhagic-prone cerebral angiopathy, such as hypertensive and amyloid angiopathies [2,4,5]. Similarly, spontaneous ICH occurs as the acute manifestation of a chronic cerebral vasculopathy and the most common accepted etiologies are cerebral amyloid angiopathy (CAA) for lobar ICH and hypertension for deep ICH [6].…”