TNK Group Research Articles

Tenecteplase versus alteplase before mechanical thrombectomy: experience from a US healthcare system undergoing a system-wide transition of primary thrombolytic

BackgroundTenecteplase (TNK) is a genetically modified variant of alteplase (TPA) and has been established as a non-inferior alternative to TPA in acute ischemic stroke (AIS). Whether TNK exerts distinct benefits...

Abstract 44: Safety Of Tenecteplase And Alteplase In Tandem Lesion Stroke: A Pooled Analysis Of The Extend-IA TNK Trials

Introduction: The efficacy of tenecteplase (TNK) in patients with tandem lesions (TL) in the anterior circulation is unknown. The longer half-life of TNK could potentially lead to increased hemorrhage, especially in patients who require stenting of the extracranial internal carotid artery (eICA) and subsequent antiplatelet therapy. We assessed the efficacy and safety of TNK in a pooled analysis of the EXTEND-IA TNK trials. Methods: We compared the treatment effect of TNK (pooled analysis of 0.25 and 0.40mg/kg dosing) with alteplase (tPA), stratifying for TL presence. A TL was defined as a combination of eICA pathology (ipsilateral stenosis >70% or occlusion) and intracranial LVO. Outcomes evaluated include 90-day mRS, intracranial reperfusion at initial angiographic assessment, mortality, ICH (symptomatic [sICH] and parenchymal hematoma [PH]). Treatment effect was adjusted for baseline NIHSS, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models. Results: Of 483 patients with an anterior circulation occlusion, 71/483 (15%) patients had a TL and 43/71 (61%) patients required eICA stenting. In TL patients, reperfusion at initial angiographic assessment was observed in 11/56 (20%) of patients treated with TNK vs. 1/15 (7%) patients treated with tPA (aOR:3.71; 95% CI:0.42-32.75). sICH was observed in 4/71(6%) TL vs 7/412 (2%) nonTL patients (p=0.04). Among TL patients, sICH occurred in 4/56 (7%) patients treated with TNK vs 0/15 (0%) tPA treated patients (p=0.57); sICH occurred in 2/40 (5%) of the 0.25mg/kg TNK group and 2/16 (12.5%) of the 0.40mg/kg TNK group. PH was observed in 6/56 (11%) patients treated with TNK vs 0/15 (0%) tPA treated patients (p=0.33). 90-day mRS (TNK median 2 vs. tPA median 4, acOR:1.21; 95% CI:0.42-3.48), mortality (TNK: 5 [9%] vs. tPA: 3 [20%], aOR:0.45; 95% CI:0.08-2.50), and eICA stenting (TNK: 35 [64%] vs. tPA: 8 [57%], p=0.65) rates did not differ between the two treatment groups. Conclusions: Although patients with TL in the anterior circulation were at higher risk of hemorrhagic complications, these did not significantly differ between the TNK and tPA groups. A numeric increase in bleeding with TNK was not accompanied by an increase in mortality or worse functional outcome.

Abstract 43: Comparative Effectiveness Of Routine Tenecteplase Thrombolysis In Acute Stroke Compared With Alteplase: An INternational Collaboration (CERTAIN Collaboration): Rates Of Symptomatic Intracranial Hemorrhage

Introduction: Despite pharmacological and practical advantages for tenecteplase (TNK) over alteplase (ALT), no differences were observed in percent of symptomatic intracranial hemorrhage (sICH) in randomized trials (fewer than 900 total patients for either treatment). We compared rates of sICH in patients treated with either drug, using a large, multicenter, international registry. Methods: The CERTAIN collaboration is an ongoing registry of deidentified patient-level data of thrombolytic treated ischemic stroke from various hospitals/programs in New Zealand, Australia, and the United States that have used ALT or TNK since July 1, 2018. Standardized data were abstracted and harmonized from local or regional clinical registries. We defined sICH as clinical worsening of at least 4 points on NIHSS, attributed to parenchymal hematoma, subarachnoid or intraventricular hemorrhage. We used logistic regression for binary variables, adjusting sICH differences for age, baseline NIHSS, thrombectomy, and source hospital network and Mann-Whitney test for continuous baseline variables. Results: A total of 7891 patients were included in the initial analysis. The TNK group was older, more likely to be male, had higher NIHSS, and more frequently underwent mechanical thrombectomy (Table. Sample Characteristics). The sICH rate was 3.71% for ALT and 2.13% for TNK: adjusted OR (95%CI) = 0.49 (0.31-0.76) p=0.002. For patients not undergoing thrombectomy after thrombolytic, the sICH rate was 3.00% for ALT and 1.74% for TNK, adjusted OR (95%CI) = 0.48 (0.27-0.87), p=0.016. For thrombectomy treated cases, sICH rate was 6.80% for ALT and 2.80% for TNK, adjusted OR (95%CI) 0.60 (0.31-1.16), p=0.129. Conclusion: In this preliminary analysis from a large, multicenter registry, ischemic stroke treated with tenecteplase was associated with a lower rate of sICH than with alteplase. An updated analysis with patient data from additional sites will be presented at the Conference.

Tenecteplase and Alteplase for Thrombolysis of Acute Ischemic Stroke within 4.5 Hours: An Efficacy and Safety Study.

To compare the efficacy and safety of thrombolysis using Tenecteplase (TNK) versus alteplase in acute ischaemic stroke (AIS) patients within 4.5-hour window period. This retrospective study involved the collection of data from consecutive AIS patients who underwent thrombolysis in the Department of Neurology at a tertiary care university hospital, between May 2018 to January 2021. Data including clinical history, neurological assessment using modified Rankin score (mRS), National Institutes of Health Stroke Scale (NIHSS), brain neuroimaging, treatment, and outcome details were collected. The primary efficacy outcome was the proportion of patients with good functional recovery (mRS of 0-2) at 90 days of follow-up. Total of 42 patients with AIS underwent thrombolysis, of which 19 received alteplase and 23 got TNK. The median (range) onset to door time [120 (20-210) versus 120 (30-210) minutes; P = 0.823] and median (range) onset to needle time [150 (60-255) versus 160 (50-240) minutes; P = 0.779] were comparable in both alteplase and TNK groups, respectively. The primary outcome of good functional recovery (mRS ≤2) at 3 months was observed in more than half the patients in each group and was comparable (P = 0.701). Post-thrombolysis complications including cerebral haemorrhage (symptomatic or asymptomatic) were comparable between the two groups (31.6% vs 30.4%; P = 0.936), except a significantly higher proportion of patients on TNK required mechanical ventilation (10.5% v/s 43.5%; P = 0.019). This study showed a comparable efficacy and safety profile of alteplase and TNK in thrombolysis of AIS throughout the 4.5 hours window period. Moreover, the ease of administration and better pharmacodynamic properties favors tenecteplase.

Abstract P381: Pre-Treatment Perfusion Mismatch Volumes in Ischemic Stroke Patients Treated With Tenecteplase or Alteplase

Introduction: The overall goal of this study is to evaluate the relationship of pretreatment perfusion mismatch volumes to outcomes in patients receiving alteplase (ALT) to those receiving tenecteplase (TNK). Methods: This study included patients receiving treatment with ALT (0.9 mg/kg; max, 90 mg) or TNK (0.25 mg/kg; max, 25 mg) between 09/01/2017 - 06/30/2020 identified through our local stroke registry stroke registry. Of the 505 patients meeting these criteria, 280 have been screened, including patients receiving EVT (n=94) and a sampling of n=111 from the ALT group and 75 from the TNK group. Final eligibility will be patients with a pretreatment perfusion deficit, mismatch > 15 mL, and mismatch (MM) ratio ≥ 1.2. Volumes are based on RAPID software (iSchemiaView). Using univariate (chi-squared with continuity correction or Mann-Whitney U) and adjusted logistic models, the effect of lysis type and pre-treatment imaging were assessed on the primary outcome of discharge disposition. Results: A total of 93 patients were included in our analysis, 40 receiving ALT and 53 patients receiving TNK, demographics found in Table 1. Discharge to home occurred in 48.8% (20/40) of patients treated with ALT and 30.7% (16/53) treated with TNK, odds ratio (OR), 0.47; 95% CI [0.20, 1.09], (P-value for OR=0.0766). Upon adjustment for EVT, age, sex, NIHSS on admission, imaging modality, cohort imbalances (marked by *), and MM, the relation of lysis type to discharge to home gave an OR of 0.25; 95% CI [0.06, 0.90], P= 0.0383) with age (P<0.0001) and imaging modality (P=0.0020) significantly contributing to the model. Lysis type did not significantly influence discharge to hospice or death (OR, 0.62; 95% CI [0.05, 6.86], P=0.6945) upon adjustment for baseline factors. Conclusion: In this preliminary analysis, MM volumes did not contribute to the outcome of discharged to home. Analysis of the full cohort is ongoing and final analyses will relate lytic type to infarct volume growth and clinical outcomes.

In vitro examination of the thrombolytic efficacy of tenecteplase and therapeutic ultrasound compared to rt-PA

BackgroundOptimizing thrombolytic therapy is vital for improving stroke outcomes. We aimed to develop standardized thrombolysis conditions to evaluate the efficacy of tenecteplase (TNK) compared to the current gold standard rt-PA (alteplase), with and without additional ultrasound treatment. We also wanted to introduce a new analytical approach to quantify fibrin fiber density in transmission electron microscopy (TEM).MethodsIn vitro clots that are similar to ex vivo clots concerning their histological condition and their durability were generated from whole blood. For five treatment groups we compared relative clot weight loss (each n = 60) and fibrin fiber density in TEM (each n = 5). The control group (A) was treated only with plasma. Two groups were designated for each rt-PA (B + C) and TNK (D + E). Groups C and E were additionally treated with ultrasound. Dosages were 50 μg/ml for rt-PA and 30 μg/ml for TNK. Results were evaluated by using analyses of variance (ANOVA) and post-hoc t-tests.ResultsWeight loss was increased significantly for all groups compared to the control group. Both TNK groups showed significantly increased weight loss compared to their counterpart rt-PA group (p ≤ 0.001). For TEM only group D showed significantly decreased fibrin fiber density (p < 0.05) compared to both rt-PA groups. Ultrasound did not significantly increase dissolution of clots with either method (best p = 0.16).ConclusionsTenecteplase dissolved clots more effectively than rt-PA with and without ultrasound. A higher sample size could provide more convincing results for TEM.

Penumbral Imaging-Based Thrombolysis with Tenecteplase Is Feasible up to 24 Hours after Symptom Onset.

BACKGROUND AND PURPOSE Thrombolysis >4.5 hours after ischemic stroke onset is unproven. We assessed the feasibility of tenecteplase (TNK) treatment in patients with evidence of an ischemic penumbra 4.5 to 24 hours after onset. METHODS Acute ischemic stroke patients underwent perfusion computed tomography (CT)/magnetic resonance imaging. Patients with cerebral blood volume (CBV) or diffusion weighted imaging Alberta Stroke Program Early CT Scores (ASPECTS) >6 and mismatch score >2 (defined as >2 ASPECTS regions with delay on mean transit time maps and normal CBV) were eligible for treatment with TNK (0.25 mg/kg). Patients with mismatch patterns enrolled in non-endovascular/non-thrombolysis trials and those without mismatch patterns served as comparators. RESULTS The median (interquartile range) baseline National Institutes of Health Stroke Scale (NIHSS) in TNK treated patients (n=16) was 12 (range, 8 to 15). In the untreated mismatch (n=18) and nonmismatch (n=23) groups, the baseline NIHSS was 12 (range, 7 to 12) and 16 (range, 8 to 20; P=0.09) respectively. There was one symptomatic hemorrhage each in the TNK group (parenchymal hematoma [PH] 2) and non-mismatch group (PH 2). Penumbral salvage volumes were higher in TNK treated patients (48.3 mL [range, 24.9 to 80.4]) than the non-mismatch (-90.8 mL [range, -197 to -20]; P<0.0001) patients. CONCLUSIONS This prospective, non-randomized study supports the feasibility of TNK therapy in patients with evidence of ischemic penumbra 4 to 24 hours after onset.

Penumbral Imaging-Based Thrombolysis with Tenecteplase Is Feasible up to 24 Hours after Symptom Onset.

Background and Purpose Thrombolysis >4.5 hours after ischemic stroke onset is unproven. We assessed the feasibility of tenecteplase (TNK) treatment in patients with evidence of an ischemic penumbra 4.5 to 24 hours after onset.Methods Acute ischemic stroke patients underwent perfusion computed tomography (CT)/magnetic resonance imaging. Patients with cerebral blood volume (CBV) or diffusion weighted imaging Alberta Stroke Program Early CT Scores (ASPECTS) >6 and mismatch score >2 (defined as >2 ASPECTS regions with delay on mean transit time maps and normal CBV) were eligible for treatment with TNK (0.25 mg/kg). Patients with mismatch patterns enrolled in non-endovascular/non-thrombolysis trials and those without mismatch patterns served as comparators.Results The median (interquartile range) baseline National Institutes of Health Stroke Scale (NIHSS) in TNK treated patients (n=16) was 12 (range, 8 to 15). In the untreated mismatch (n=18) and nonmismatch (n=23) groups, the baseline NIHSS was 12 (range, 7 to 12) and 16 (range, 8 to 20; P=0.09) respectively. There was one symptomatic hemorrhage each in the TNK group (parenchymal hematoma [PH] 2) and non-mismatch group (PH 2). Penumbral salvage volumes were higher in TNK treated patients (48.3 mL [range, 24.9 to 80.4]) than the non-mismatch (–90.8 mL [range, –197 to –20]; P<0.0001) patients.Conclusions This prospective, non-randomized study supports the feasibility of TNK therapy in patients with evidence of ischemic penumbra 4 to 24 hours after onset.

Tenecteplase versus streptokinase thrombolytic therapy in patients with mitral prosthetic valve thrombosis

ObjectiveProsthetic valve thrombosis (PVT) is a dreadful complication of mechanical prosthetic valves. Thrombolytic therapy (TT) for PVT is an alternative to surgery and currently making a leading role. This study compares TT with tenecteplase (TNK) and streptokinase (SK) head to head in patients with mitral PVT. MethodsIn this single center, observational study, patients with mitral PVT diagnosed by clinical data, transthoracic echocardiography, transesophageal echocardiography, and fluoroscopy were included. After excluding patients with contraindications for thrombolysis, they were randomly assigned to receive either SK or TNK regimen. Patients were monitored for success or failure of TT and for any complications. ResultsAmong 52 episodes (47 patients with 5 recurrences) of mechanical mitral PVT, 40 patients were thrombolyzed with SK and 12 patients were thrombolyzed with TNK. Baseline characteristics including demographic profile, clinical and echocardiographic features, and valve types were not statistically significant between the groups. Complete success rate was 77.5% in SK group and 75% in TNK group (p=0.88). Partial success rate, failure rate, and major complications were not statistically significant between the two groups. Within 12h of therapy, TNK showed complete success in 33.3% of patients compared to 15% in SK group (p-value <0.02). Minor bleeding was more common in TNK group. ConclusionSlow infusion of TNK is equally efficacious but more effective than SK in the management of mitral mechanical PVT. 75% to 77.5% of PVT patients completely recovered from TT and it should be the first line therapy where the immediate surgical options were remote.

Abstract W MP31: Penumbral Imaging-Based Thrombolysis with Tenecteplase is Feasible Up to 24 Hours After Symptom Onset

Introduction: Penumbral imaging-based selection of patients for thrombolysis with tenecteplase (TNK) has been shown to be feasible up to 6 h after onset. We aimed to demonstrate the feasibility and safety of thrombolysis in ischemic stroke patients with penumbral patterns presenting 4.5-24 h after symptom onset. Methods: We conducted an open label single arm trial. Acute ischemic stroke patients presenting between 4.5-24 h after symptom onset were assessed with perfusion imaging. Patients with pretreatment perfusion CT/MRI that demonstrated a perfusion deficit volume &gt;15 ml and penumbra volume &gt;20% of the infarct core were eligible for TNK treatment. They received 0.25 mg/kg IV TNK. The primary outcome was symptomatic hemorrhagic transformation. Patients screened with perfusion CT/MRI who met trial criteria, but were not enrolled in the study, formed a parallel cohort. Results: A total of 26 patients were screened with perfusion CT/MRI. Thirteen patients received TNK (mean±SD age = 62±12 y). The 13 parallel cohort patients were of similar age (55±18 y, p=0.257). Median (IQR) baseline NIHSS in TNK treated patients (13(9)) was similar to that in the parallel cohort (14(10), p=1.00). Median time to TNK treatment was 8.7 h(range: 5.1-23.3). Reperfusion and recanalization occurred in 54.5% and 50% of TNK treated patients at 24 h, respectively. Infarct growth at 24 h was attenuated in TNK treated patients (8.7 (31.3) ml) relative to the parallel cohort (53.0 (91.5) ml, p=0.017). Penumbral salvage volume was greater in TNK treated patients (51.7 (58.2) ml) than parallel cohort patients (-16.7 (112.2) ml, p=0.001). There was one symptomatic hemorrhage in the TNK group (ECASS grade PH1). Two other TNK treated patients developed asymptomatic hemorrhages (ECASS grade PH1). The rate of good functional outcome (modified Rankin Score ≤2) at day 90 was greater in TNK patients (8/12, 66.7%) than in the parallel cohort (2/13, 15.3%, p=0.015). Conclusion: Thrombolysis with TNK treatment in appropriately selected patients is feasible even up to 24 hours after onset. Randomized studies of penumbral imaging-based selection of TNK candidates in an extended therapeutic time window are warranted.

Thrombolysis With Single Bolus Tenecteplase Compared With Streptokinase Infusion in the Treatment of Acute Pulmonary Embolism

This study was planned to compare the efficacy of bolus regimens of tenecteplase (TNK) and 24 hours infusion of streptokinase (STK) in acute pulmonary embolism (APE) in a resource-poor setting. In all, 25 patients received injection of TNK, and 75 patients received infusion of STK over 24 hours. Pulmonary artery systolic pressure and right ventricular function were improved separately and significantly (P = .01) in both the study groups of patients from baseline at 24 hours or at seventh day and was comparable among the TNK and STK groups of patients. Mean duration of stay in intensive care unit was significantly less (2.2 ± 0.8 vs 3.2 ± 1.3 days; P = .04), and bleeding risk was also found to be nonsignificantly less in the TNK group. These results suggest that a 24-hour infusion regimen of STK is as effective as bolus TNK in the treatment of patients with APE in countries with limited resources.

Efficacy and Safety of Tenectaplase versus Streptokinase in Treating ST-Elevation Myocardial Infarction Patients in Hong Kong: A Four-Year Retrospective Review in Queen Elizabeth Hospital

Objective Data were lacking in comparing tenectaplase (TNK) and streptokinase (SK) in treating Chinese ST elevation myocardial infarction (STEMI) patients. We sought to compare these 2 types of thrombolytics in our locality. Methods We analysed 196 STEMI patients who received either TNK or SK in our hospital from 2007 to 2011. We compared the mortality and other outcomes of these 2 groups of patients. Results In-hospital mortality has no significant difference between the TNK and the SK groups (8.9% vs 5.3%, p=0.322). Door-to-needle time was shorter in the TNK group (31±10 vs 25±7, p&lt;0.001). Hypotension after drug administration was more common in the SK group than in the TNK group (21.1% vs. 3.0%, p&lt;0.001). Conclusion TNK is at least as safe as SK in treating STEMI patients, with the advantage of shorter door-to-needle time and less frequent hypotensive effect. (Hong Kong j.emerg.med. 2013;20:359-363)

Efectividad y seguridad de la alteplasa frente a la tenecteplasa en la fibrinólisis del síndrome coronario agudo con elevación de ST

Introduction The importance of early administration of fibrinolytic therapy in ST elevated myocardial infarction (STEMI), with the aim of reducing mortality, is universally accepted and endorsed by many publications. Our objective was to determine whether the fibrinolytic reperfusion with tenecteplase (TNK) was less effective than that obtained with alteplase (rt-PA), and also to analyse the safety of both agents. Methodology A retrospective observational study was conducted on patients admitted to our ICU between 2005-2008 due to an STEMI, and treated with one of these two thrombolytic agents. Clinical and angiographic criteria data were used to evaluate the effectiveness of fibrinolysis, bleeding complications and the intra-ICU mortality rate. Results Of the 453 patients who met the inclusion criteria, 286 were treated with TNK and 167 with rt-PA. Both groups were homogeneous and no difference was found between them regarding the effectiveness parameters (pain management, myoglobin ratio or ST depression). Artery re-occlusion in patients who already met the criteria for effective fibrinolysis was higher in the TNK group (22.5% vs. 11.6%, P=.04). In the 346 patients who underwent coronary angiography within 72 h (203 in the group treated with TNK and 143 in the group treated with rt-PA), closed arteries were open (TIMI 3) in 28.4% and 53.9% respectively ( P=.001). There were no significant differences in bleeding complications between both groups, however less bleeding was observed with TNK. There were no differences in mortality rate between both groups. Conclusions Both drugs showed a similar rate of reperfusion, although there was a smaller percentage of re-occlusions with rt-PA. The complication rate did not differ in both groups, although TNK seemed to be less harmful, especially at the expense of extracranial bleeding.

Effect of internal carotid artery reperfusion in combination with Tenecteplase on clinical scores and hemorrhage in a rabbit embolic stroke model

In the present study, we used a modification of the rabbit small clot embolic stroke model (RSCEM), a multiple infarct ischemia model to achieve reperfusion (REP) through the internal carotid artery (ICA) following small clot embolization. We determined if increasing regional cortical blood flow (RCBF) following an embolic stroke is beneficial to neurological outcome. We compared this to cerebral reperfusion induced by the administration of the thrombolytic Tenecteplase (TNK, 1.5 mg/kg, IV bolus) in the presence or absence of REP. In this study, we also measured the incidence of ICH following REP and thrombolytic treatment. Following embolization, RCBF was reduced to 48–55% of baseline. When REP was induced by removal of a CCA ligature, RCBF initially increased to 185% of baseline. REP (P 50 = 1.18 ± 0.43 mg) had no effect on embolization-induced behavior measured 24 h following embolization compared to control (P 50 = 1.01 ± 0.48 mg). However, TNK treatment (2-hours post-embolization) in the absence or presence of REP (initiated 2 h following embolization) significantly ( p < 0.05) increased the group P 50 to 2.92 ± 0.55 mg and 2.42 ± 0.40 mg, respectively. In addition, ICH was increased in the REP (42%, p < 0.05) and REP-TNK (35%, p > 0.05) group compared to either the control group (5.5%) or TNK group (10%). This study show that reperfusion of ICA can increase RCBF following embolization, but this is not associated with improved neurological outcome measured using quantal analysis. However, TNK administration significantly increased behavioral outcome when given 2 h following embolization; an increase that is not affected by combining TNK with REP.

Effect of tenecteplase versus alteplase on platelets during the first 3 hours of treatment for acute myocardial infarction: The Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) platelet substudy

Background Platelets play a pivotal role in the pathogenesis of acute myocardial infarction, as well as in the occurrence of coronary artery reocclusion and bleeding events. Therefore, the success of fibrinolytic therapy may be dependent on its direct effects on platelets. Methods and Results We sought to determine how tenecteplase (TNK) and alteplase (tPA) affect platelets in vitro in human volunteers and ex vivo by use of patient data from the Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) trial. For the in vitro studies, whole blood from 9 healthy volunteers was incubated with 30 mg TNK and 60 mg tPA. Platelet function was measured by conventional aggregometry, bedside point-of-care devices, and sensitive flow cytometry techniques. For the ex vivo study, 41 patients were selected from the ASSENT-2 trial: 21 had received TNK and 20 had received tPA. Each patient underwent 7 serial blood draws every 30 minutes for 3 hours. Levels of platelet endothelial cell adhesion molecule-1 (PECAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, β-thromboglobulin, platelet factor 4, thromboxane, and prostacyclin were measured by enzyme-linked immunosorbent assay. Significant inhibition of conventional and whole blood aggregation and reduced platelet function by point-of-care analyzers were observed for both agents, but mostly in the TNK-treated samples. After incubation with TNK, flow cytometry revealed decreased expression of glycoprotein IIb/IIIa, PECAM-1, vitronectin receptor, CD151, and formation of the platelet-monocyte aggregates. Serial samples from patients in the ASSENT-2 trial showed a significant decrease of soluble platelet-endothelial biomarkers in the TNK group. There was a trend toward decreased platelet function characteristics with tPA; however, these differences were much smaller than those observed with TNK. Conclusions Both tPA and TNK were shown to affect platelet function in human volunteers and in patients with AMI early after thrombolysis. The antiplatelet properties of TNK were shown to be more profound than those of tPA. These findings are relevant to ongoing investigations of combination therapy with fibrinolytic and antiplatelet agents in patients with AMI. (Am Heart J 2003;145:636-42.)