Intracranial Hemorrhage Risk in the Era of Antithrombotic Therapies for Ischemic Stroke

Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment–elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.

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Incorporation of α2-Plasmin Inhibitor into Fibrin Clots and Its Association with the Clinical Outcome of Acute Ischemic Stroke Patients

Biomolecules ◽

10.3390/biom11030347 ◽

2021 ◽

Vol 11 (3) ◽

pp. 347

Author(s):

Zsuzsa Bagoly ◽

Barbara Baráth ◽

Rita Orbán-Kálmándi ◽

István Szegedi ◽

Réka Bogáti ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Intravenous Thrombolysis ◽

Fibrin Clot ◽

Clot Lysis ◽

Stroke Patients ◽

Plasmin Inhibitor ◽

Fibrin Clots

Cross-linking of α2-plasmin inhibitor (α2-PI) to fibrin by activated factor XIII (FXIIIa) is essential for the inhibition of fibrinolysis. Little is known about the factors modifying α2-PI incorporation into the fibrin clot and whether the extent of incorporation has clinical consequences. Herein we calculated the extent of α2-PI incorporation by measuring α2-PI antigen levels from plasma and serum obtained after clotting the plasma by thrombin and Ca2+. The modifying effect of FXIII was studied by spiking of FXIII-A-deficient plasma with purified plasma FXIII. Fibrinogen, FXIII, α2-PI incorporation, in vitro clot-lysis, soluble fibroblast activation protein and α2-PI p.Arg6Trp polymorphism were measured from samples of 57 acute ischemic stroke patients obtained before thrombolysis and of 26 healthy controls. Increasing FXIII levels even at levels above the upper limit of normal increased α2-PI incorporation into the fibrin clot. α2-PI incorporation of controls and patients with good outcomes did not differ significantly (49.4 ± 4.6% vs. 47.4 ± 6.7%, p = 1.000), however it was significantly lower in patients suffering post-lysis intracranial hemorrhage (37.3 ± 14.0%, p = 0.004). In conclusion, increased FXIII levels resulted in elevated incorporation of α2-PI into fibrin clots. In stroke patients undergoing intravenous thrombolysis treatment, α2-PI incorporation shows an association with the outcome of therapy, particularly with thrombolysis-associated intracranial hemorrhage.

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P-003 Association between baseline serology and symptomatic intracranial hemorrhage after endovascular thrombectomy for acute ischemic stroke

10.1136/neurintsurg-2021-snis.39 ◽

2021 ◽

Author(s):

J Diestro ◽

C Parra-Farinas ◽

M Balas ◽

Z Zador ◽

N Almusalam ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Endovascular Thrombectomy ◽

Symptomatic Intracranial Hemorrhage

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Characteristics of ischemic stroke and intracranial hemorrhage in patients with nephrotic syndrome

BMC Nephrology ◽

10.1186/s12882-021-02415-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Wen-Yi Huang ◽

Chun-Wei Chang ◽

Chiung-Mei Chen ◽

Kuan-Hsing Chen ◽

Chien-Hung Chang ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Cox Regression ◽

Hazard Ratio ◽

Chang Gung Memorial Hospital ◽

Cerebral Stroke ◽

Research Database ◽

Anterior Circulation ◽

Cox Regression Analysis

Abstract Background The incidence of cerebral stroke, including ischemic infarction and intracranial hemorrhage (ICH), increases in patients with nephrotic syndrome (NS). However, the clinical characteristics of patients with NS and stroke remain elusive. We aimed to investigate the clinical presentation and prognosis among patients with NS and ischemic stroke (IS) or ICH. Methods We conducted a population-based retrospective cohort study of patients with NS and acute stroke using the Chang Gung Research Database of Taiwan from January 1, 2001, to December 31, 2017. The participants were recruited from the 7 branches of Chang Gung Memorial Hospital. Results A total of 233 patients with IS and 57 patients with ICH were enrolled. The median age was 60 (52–70) years. The prevalence rates of hyperlipidemia, hyperuricemia, and smoking were higher in IS than in ICH. IS demonstrated lower white blood cell count (7.80 vs. 8.92 × 109/L) and high-sensitivity C-reactive protein level (33.42 vs. 144.10 nmol/L) and higher cholesterol (5.74 vs. 4.84 mmol/L), triglyceride (1.60 vs. 1.28 mmol/L), and albumin (24 vs. 18 g/L) levels compared with ICH. The dependent functional status and 30-day mortality were higher in ICH than in IS. The risk factors for 30-day mortality for patients with NS and stroke were coronary artery disease (CAD), ICH, and total anterior circulation syndrome. The multivariate Cox regression analysis revealed that CAD was positively associated with 30-day mortality in patients with IS (hazard ratio 24.58, 95 % CI 1.48 to 408.90). In patients with ICH, CAD and subarachnoid hemorrhage were positively associated with 30-day mortality (hazard ratio 5.49, 95 % CI 1.54 to 19.56; hazard ratio 6.32, 95 % CI 1.57 to 25.53, respectively). Conclusions ICH demonstrated a higher risk of dependence and 30-day mortality compared with IS in patients with NS. Intensive monitoring and treatment should be applied particularly in patients with NS and ICH.

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Bivalirudin for Endovascular Intervention in Acute Ischemic Stroke: Case Report

Neurosurgery ◽

10.1227/01.neu.0000097556.08044.1f ◽

2004 ◽

Vol 54 (1) ◽

pp. 218-223 ◽

Cited By ~ 18

Author(s):

Mark R. Harrigan ◽

Elad I. Levy ◽

Bernard R. Bendok ◽

L. Nelson Hopkins

Keyword(s):

Ischemic Stroke ◽

Middle Cerebral Artery ◽

Acute Ischemic Stroke ◽

Scale Score ◽

Intracranial Hemorrhage ◽

National Institutes Of Health ◽

Left Middle Cerebral Artery ◽

Computed Tomographic ◽

Left Middle ◽

Arterial Thrombolysis

Abstract OBJECTIVE AND IMPORTANCE Intra-arterial thrombolysis has been demonstrated to improve recanalization and outcomes among patients with acute ischemic stroke. However, thrombolytic agents have limited effectiveness and are associated with a significant risk of bleeding. Bivalirudin is a direct thrombin inhibitor that has been demonstrated in the cardiology literature to have a more favorable efficacy and bleeding profile than other antithrombotic medications. We report the use of bivalirudin during endovascular treatment of acute stroke, when hemorrhagic complications are not uncommon. CLINICAL PRESENTATION A 71-year-old woman with atrial fibrillation presented with right hemiparesis and aphasia and was found to have a National Institutes of Health Stroke Scale score of 10. Computed tomographic scans revealed no evidence of intracranial hemorrhage, aneurysm, or ischemic stroke. Cerebral angiography revealed thromboembolic occlusion of the superior division of the left middle cerebral artery. INTERVENTION For anticoagulation, a loading dose of bivalirudin was intravenously administered before the interventional procedure, followed by continuous infusion. Attempts to remove the clot with an endovascular snare failed to induce recanalization of the vessel. Bivalirudin was then administered intra-arterially. Immediate postprocedural angiography demonstrated restoration of flow in the left middle cerebral artery. Repeat computed tomographic scans demonstrated no intracranial hemorrhage. The patient's hemiparesis and aphasia were nearly resolved and her National Institutes of Health Stroke Scale score was 2 at the time of her discharge 5 days later. CONCLUSION To our knowledge, this is the first report of the use of bivalirudin for treatment of acute ischemic stroke. Bivalirudin may be a useful agent for intravenous anticoagulation and intra-arterial thrombolysis in this setting.

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