Now what do you do? Call the chaplain? Is there anything else we can do to reverse the effects of tPA? Finding that balance between improving outcomes in acute ischemic stroke, while seeking to limit adverse effects, has been quite difficult.
In select patient populations the benefit of this therapy exceeds the risk. Although it occurs in a minority of patients, ICH post administration of tPA can be quite catastrophic. Knowing the next steps in these time-sensitive moments is a cornerstone of management. The first step in treating a post-tPA hemorrhage starts before stroke treatment : tPA should be avoided in high-risk scenarios, and each patient should be risk stratified prior to tPA infusion.
High risk factors include an elevated glucose or a history of diabetes, a high National Institutes of Health Stroke Scale NIHSS score, advanced age, elevated blood pressure, thrombocytopenia, and any history of congestive heart failure. An article by Saver, et al in Stroke in defined the number needed to harm with tPA. Provided that a patient is selected that is consistent with the NINDS trial, for every people treated with tPA, there would be about 2.
Harm was defined as an increase in at least one point on the modified Rankin scale. On the other side, about 16 people per hundred will benefit from treatment.
What if a hemorrhage does occur? In in the journal Neurocritical Care , Norby, et al looked at that very question in regard to prognosis. Unfortunately for patients with symptomatic intracerebral hemorrhage sICH after receiving tPA, there is a paucity of data to support any one therapeutic intervention. We are limited to case reports and theoretical recommendations from experts.
The American Heart Association and American Stroke Association guidelines for management of ischemic stroke note there is no standardized protocol or guideline for managing these patients.
Tissue plasminogen activator works by converting plasminogen to plasmin, which subsequently degrades fibrin. Anti-fibrinolytics work in the opposite manner by competitively inhibiting the activation of plasminogen to plasmin. In one of its largest trials, TXA was shown to reduce the risk of all-cause mortality in bleeding trauma patients. This study showed neither a benefit nor detrimental effect on ICH. A head CT obtained 3 hours later revealed no further expansion of the bleeding.
The eligibility of each admission is confirmed through chart review. Standardized data collection includes patient demographics, medical history, diagnostic testing, brain imaging, in-hospital treatment, and outcomes. The GWTG-Stroke Registry collects data on medications prior to admission, including use of antithrombotics, type of antithrombotic eg, antiplatelet agent or anticoagulant , and INR values at presentation, using a new version of the data collection form made available in April The Duke Clinical Research Institute serves as the data analysis center and has an agreement to analyze the aggregate deidentified data for research purposes.
We excluded patients who had missing information on warfarin use and INR. We further limited our primary analyses to patients presenting with a baseline INR of 1. After these exclusions, our primary study population consisted of 23 patients from hospitals Figure 1.
Warfarin treatment was defined as a patient taking warfarin within 7 days of the index stroke admission. The baseline INR results refer to the first measurement after presentation to the hospital. Quiz Ref ID The primary outcome measure was sICH, defined as intracerebral hemorrhage within 36 hours, documented by computed tomography or magnetic resonance imaging and by the treating physician's notes indicating clinical deterioration attributable to hemorrhage. Any tPA complication includes sICH within 36 hours, life-threatening or serious systemic hemorrhage within 36 hours, or other serious complications.
Means, medians, and percentages were used to describe the distribution of continuous and categorical variables, respectively. Multivariable logistic regression analyses were performed to investigate the relationships between warfarin use and tPA-related complications of 1 sICH, 2 life-threatening or serious systemic hemorrhage, and 3 any tPA complication.
The mortality model adjusted for age, sex, arrival mode, medical history of atrial fibrillation, coronary artery disease, prior stroke or transient ischemic attack TIA , diabetes mellitus, dyslipidemia, and NIHSS score. Our analyses also accounted for within-hospital clustering using a generalized estimating equations approach. The robustness of our findings was assessed in several ways.
First, we performed a sensitivity analysis using a logistic regression model with all aforementioned clinical factors except for NIHSS score. Fourth, given that the population of greatest interest may be those with higher INR levels, we performed a subgroup analysis focused on patients presenting with INRs between 1. We compared clinical factors between warfarin-treated patients treated with tPA vs those not. The association of INR and risk for sICH among warfarin-treated patients was examined graphically and tested for linearity.
We then conducted a multivariable analysis including INR and the aforementioned other intracerebral hemorrhage risk factors to determine whether any association between INR and sICH risk persisted after risk adjustment. Because INR is an exponential measure of the ratio of a patient's prothrombin time to normal, we repeated the analysis based on log INR. In a separate analysis, we determined the percentage of patients with ischemic stroke receiving warfarin therapy in the GWTG-Stroke Registry who were otherwise eligible for intravenous tPA but did not receive it.
All statistical analyses were performed using SAS version 9. The institutional review board of the Duke University Health System approved the study; patient informed consent was not required. Among 23 patients receiving intravenous tPA, 7. Table 1 and Table 2 report demographic, clinical, and hospital characteristics. The baseline INR levels were higher in warfarin-treated patients median, 1. We found generally similar demographic, medical history, and clinical characteristics among the tPA-eligible warfarin-treated patients who received tPA vs those who did not eTable.
Therefore, we found no evidence for preferential treatment of warfarin-treated patients with a lower propensity for tPA-related sICH.
Overall, patients 4. Warfarin-treated patients had a higher overall unadjusted rate of sICH than did non—warfarin-treated patients 5. However, after risk adjustment, warfarin use was not an independent predictor of sICH risk adjusted OR, 1.
These relationships between warfarin use and sICH were consistent in sensitivity analysis Table 4. Our results also remained essentially unchanged in patients with complete NIHSS data warfarin-treated and 19 non—warfarin-treated patients; unadjusted sICH rates, 5. Further adjustment for use of antiplatelet therapy prior to admission did not substantially alter the association of warfarin and sICH adjusted OR, 1.
The rates of life-threatening or serious systemic hemorrhage were similar in both groups 0. However, after multivariable adjustment, warfarin use was not associated with life-threatening or serious systemic hemorrhage adjusted OR, 0. Among patients who survived, there was no significant difference in rates of discharge to a rehabilitation facility adjusted OR, 1.
However, warfarin-treated patients were more likely to be discharged to a skilled nursing facility adjusted OR, 1. We also grouped the INR into 3 categories 0. Overall, of the patients in the 0-hours to 3-hours time window and of the patients in the 3-hours to 4. Among these patients, Collectively, Quiz Ref ID In this large nationwide contemporary registry of patients with acute ischemic stroke, we found that use of intravenous tPA among warfarin-treated patients with a baseline INR of 1.
These findings were robust across several subgroup analyses and risk-adjustment methods. Warfarin use was also not associated with life-threatening or serious systemic hemorrhage, any tPA complication, or in-hospital mortality. Symptomatic intracranial hemorrhage is the most feared complication of thrombolysis for acute ischemic stroke. Despite lack of safety data, intravenous tPA has been used in patients receiving warfarin in clinical practice.
To date, only a few studies have investigated the safety of tPA treatment among warfarin-treated patients, with conflicting and inconclusive results. Importantly, all of these studies were limited to small samples that included a total of patients receiving oral anticoagulants. Our study represents the largest clinical experience of the safety of intravenous tPA in warfarin-treated patients who meet clinical guideline eligibility criteria.
Among 23 patients with ischemic stroke treated with intravenous tPA, had taken warfarin before stroke onset. The overall sICH rate 4. After adjusting for these factors in the multivariate analysis, warfarin treatment was no longer a significant predictor of sICH.
Another explanation may be related to the intensity of anticoagulation. Studies have shown that the bleeding risk of warfarin is associated with the intensity of anticoagulation, as reflected by the INR. Our findings also suggest several new directions for outcomes-based stroke research. Although our study supports the safety of intravenous tPA for warfarin-treated patients within the guideline recommendation, it remains unclear how high the INR value could be for this safety to hold.
The subgroup analysis of patients with INRs between 1. J Neurointerv Surg. Thrombolysis with alteplase 3 to 4. N Engl J Med. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials.
Tissue plasminogen activator for acute ischemic stroke. Thrombolytic agents in the treatment of stroke. Clin Neuropharmacol. Trouillas P, von Kummer R. Classification and pathogenesis of cerebral hemorrhages after thrombolysis in ischemic stroke. Predictors of parenchymal hematoma after mechanical thrombectomy: a multicenter study. Early hemorrhagic transformation of brain infarction: rate, predictive factors, and influence on clinical outcome: results of a prospective multicenter study.
Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J Biol Chem. Fibrinogen breakdown, long-lasting systemic fibrinolysis, and procoagulant activation during alteplase double-bolus regimen in acute myocardial infarction.
Am J Cardiol. Pharmacokinetics and fibrin specificity of alteplase during accelerated infusions in acute myocardial infarction. J Am Coll Cardiol. Thrombolysis in myocardial infarction TIMI : comparative studies of coronary reperfusion and systemic fibrinogenolysis with two forms of recombinant tissue-type plasminogen activator. Fibrinogen degradation coagulopathy and bleeding complications after stroke thrombolysis. Hemorrhagic transformation in acute ischemic stroke. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke.
Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke ECASS II. Hemorrhagic transformation of ischemic brain tissue: asymptomatic or symptomatic? Early angiographic and CT findings in patients with hemorrhagic infarction in the distribution of the middle cerebral artery.
Am J Neuroradiol. PubMed Abstract Google Scholar. Hemorrhagic transformation of brain infarct: predictability in the first 5 hours from stroke onset and influence on clinical outcome. Hemorrhagic cerebral infarction—a prospective study. Hemorrhagic infarcts.
Eur Neurol. Factors related to intracranial hematoma formation in patients receiving tissue-type plasminogen activator for acute ischemic stroke. The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy.
Intra-arterial prourokinase for acute ischemic stroke. Prolyse in Acute Cerebral Thromboembolism. Prognosis of asymptomatic intracranial hemorrhage after endovascular treatment. Asymptomatic intracerebral hemorrhage may worsen clinical outcomes in acute ischemic stroke patients undergoing thrombectomy.
J Stroke Cerebrovasc Dis. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. CrossRef Full Text. Extending thrombolysis to 4. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke the third international stroke trial [IST-3] : a randomised controlled trial.
Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. MRI-guided thrombolysis for stroke with unknown time of onset. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis. Lancet Neurol.
Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Early deterioration after thrombolysis plus aspirin in acute stroke: a post hoc analysis of the antiplatelet therapy in combination with recombinant t-PA thrombolysis in ischemic stroke trial.
Predicting the risk of symptomatic intracerebral hemorrhage in ischemic stroke treated with intravenous alteplase: safe Implementation of Treatments in Stroke SITS symptomatic intracerebral hemorrhage risk score. Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies.
Intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 80 years and older: the tPA stroke survey experience.
Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian alteplase for stroke effectiveness study.
J Neurol Neurosurg Psychiatry. Thrombolysis in very elderly people: controlled comparison of SITS international stroke thrombolysis registry and virtual international stroke trials archive. Intravenous alteplase for stroke in those older than 80 years old. Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey. Age Ageing. Symptomatic intracerebral hemorrhage following thrombolytic therapy for acute ischemic stroke: a review of the risk factors.
Cerebrovasc Dis. Safety and outcomes of intravenous thrombolysis in posterior versus anterior circulation stroke: results from the safe implementation of treatments in stroke registry and meta-analysis. Maier B, Kubis N. Hypertension and its impact on stroke recovery: from a vascular to a parenchymal overview. Neural Plast. Blood pressure and clinical outcomes in the International Stroke Trial. Pre-tissue plasminogen activator blood pressure levels and risk of symptomatic intracerebral hemorrhage.
Postthrombolysis blood pressure elevation is associated with hemorrhagic transformation. Effects of blood pressure and blood pressure-lowering treatment during the first 24 hours among patients in the third International Stroke Trial of thrombolytic treatment for acute ischemic stroke.
Prognostic significance of blood pressure variability after thrombolysis in acute stroke. Reciprocal interaction of hour blood pressure variability and systolic blood pressure on outcome in stroke thrombolysis. Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke ENCHANTED : an international, randomised, open-label, blinded-endpoint, phase 3 trial.
Diabetes mellitus, admission glucose, and outcomes after stroke thrombolysis: a registry and systematic review. Exacerbation of thromboinflammation by hyperglycemia precipitates cerebral infarct growth and hemorrhagic transformation.
Am J Med. Acute reperfusion therapy and stroke care in Asia after successful endovascular trials. Predictors of hemorrhagic transformation after intravenous recombinant tissue plasminogen activator: prognostic value of the initial apparent diffusion coefficient and diffusion-weighted lesion volume. Prediction of hemorrhagic transformation following acute stroke: role of diffusion- and perfusion-weighted magnetic resonance imaging.
Arch Neurol. Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke. Risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke and high cerebral microbleed burden: a meta-analysis. JAMA Neurol. Microbleeds, cerebral hemorrhage, and functional outcome after stroke thrombolysis.
Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes. Neutrophil count predicts poor outcome despite recanalization after endovascular therapy. Intravenous thrombolysis and platelet count. Safety of intravenous thrombolysis for acute ischemic stroke in patients with thrombocytopenia.
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