Outcomes of asymptomatic recombinant tissue plasminogen activator associated intracranial hemorrhage

Abstract

Background Intracranial hemorrhage (ICH) is the most devastating complication of recombinant tissue plasminogen activator (rtPA) treatment in acute ischemic stroke patients. Data on rtPA-associated asymptomatic ICH (aICH) are limited. Objectives To determine the incidence, risk factors, characteristics, management, and clinical outcome of rtPA-associated aICH. Methods The data were retrieved from the Chiang Mai University Hospital Stroke Registry between 1995 and 2019. Consecutive ischemic stroke patients were included if they were 18 or older and received rtPA. Study outcomes were the incidence and characteristics of aICH, management, 90-day modified Rankin scale (mRS), National Institute of Health Stroke Scale (NIHSS), Barthel index, and all-cause mortality. Results Of 725 rtPA treated patients, 166 (16.0%, 95% confidence interval [CI] 13.4–18.9) had aICH, 50 (6.9%, 95% CI 5.2–9.0) had symptomatic ICH (sICH). Patients with aICH had more hemorrhagic infarctions (HI) compared to sICH (81.9% vs 2.0%, P-value < 0.001). Fresh Frozen Plasma and cryoprecipitate were the most common blood products used to reverse the anticoagulant effect in sICH. Craniotomy was performed in 1% and 60% of patients who had aICH and sICH. At 90 days, patients who had aICH had poorer clinical outcomes (mRS, NIHSS and Barthel index) as compared to those without ICH. Compared to non-ICH patients, aICH patients were associated with increased risk of 90-day mortality, the hazard ratio (HR), 3.7, 95% CI 1.6–8.9. Conclusions The rtPA-associated aICH increased the risk of morbidity and mortality outcomes. Further treatment consensus, guideline generation, or clinical trials focusing on the treatment of rtPA-associated aICH may be required.

Hemorrhage induced by Thrombolysis: new insights from a real-world pharmacovigilance study

“…IV thrombolysis with alteplase (recombinant tissue plasminogen activator, rtPA) improves the outcome of patients with ischemic stroke treated within a 4.5-hour time window(36). However, symptomatic intracranial hemorrhage occurred in 4.7-11.4% of patients treated with alteplase, and major systemic bleeding events occurred in an additional 1.6-3.6% (37,38).In our analysis, the median TTO of hemorrhage after initiation of alteplase therapy was one day and the majority occurred within the rst 24 hours, which is consistent with the earlier ndings (39,40). The mechanism of alteplase thrombolysis is the conversion of plasminogen to plasmin in the presence of brin.…”

Selective S1PR1 activation improves brain infarction, neurological outcome, and cerebrovascular endothelial health following experimental ischemic injury

“…Clinically, groundbreaking treatments like thrombolysis and mechanical clot retrieval are effective [60][61][62] ; however, these interventions are associated with high mortality risk and limit options for AIS patients as delayed hospital arrival or lack of access to a stroke center remain a concern. Fingolimod demonstrated promising therapeutic potential for AIS treatment, however due to its broad S1PR pharmacological actions, cardiac safety remains a concern.…”

Risk prediction models for intracranial hemorrhage in acute ischemic stroke patients receiving intravenous alteplase treatment: a systematic review

“…All models included in our study featured NIHSS, and meta-analysis validated that a higher NIHSS score is an independent risk factor for ICH. Whiteley WN et al conducted a meta-analysis of 55 articles on ICH risk factors in AIS patients treated with intravenous alteplase, concluding that a higher NIHSS score is a risk factor for ICH (33). Teekaput et al's retrospective study on 725 AIS patients who received alteplase treatment demonstrated that the incidence of ICH in patients with a higher baseline NIHSS was 1.9 times that of the control group (11).…”