Alteplase Thrombolysis for Acute

Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999 282 2019-2026 [see comment]. 

Three large randomized trials, the European Cooperative Acute Stroke Study (ECASS) parts I and II, and the Alteplase Thrombolysis for Acute Noninterven-tional Therapy in Ischemic Stroke (ATLANTIS), have investigated the efficacy of IV rt-PA in acute stroke beyond the 3-hour window. All three studies showed high rates of sICH complicating rt-PA treatment, and no overall efficacy of rt-PA. 

OR 1.81, 95% Cl 1.46-2.24), most of which were related to symptomatic intracranial hemorrhage (OR 3.37, 95% Cl 2.68. 22). In addition, a pooled analysis of six major randomized placebo-controlled IV rt-PA stroke trials (Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) I and II, European Cooperative Acute Stroke Study (ECASS) I and II, and NINDS I and II), including 2775 patients who were treated with IV rt-PA or placebo within 360 minutes of stroke onset, confirmed the beneht up to 3 hours and suggested a potential beneht beyond 3 hours for some patients. The pattern of a decreasing chance of a favorable 3-month outcome as the time interval from stroke onset to start of treatment increased was consistent with the findings of the original NINDS study. ... 

A pooled analysis of individual patient data from the NINDS, ECASS I and II and the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) trials (Hacke et al. 2004), which represents 99% of patients randomized in trials of rt-PA in stroke, has confirmed that benefit from thrombolysis decreases with time since stroke onset, being most beneficial if given within 90 minutes (odds ratio for favorable outcome of 2.8) (Fig. 21.1), although benefit was still present at 4.5 hours (now confirmed in ECASS III). However, it is clear that many patients will not benefit at this time point and, conversely, that other patients may benefit up to and beyond six hours in view of the fact that the ischemic penumbra may extend for much longer periods in some patients (Baron 2001). At present, only approximately 1% of UK patients receive thrombolysis (Intercollegiate Working Party on Stroke 2006) and 1-6% in North America. 

In the Alteplase ThromboLysis for Acute Non-interventional Therapy in Ischemic Stroke (ATLANTIS) Trials, patients were randomized to receive 0.9 mg/kg of rt-PA or placebo within 0-6 h (ATLANTIS-Part A n=I42) [44] or 3-5 h (ATLANTIS-Part B, n=547) [45] of stroke symptom onset. Except for time to treatment, enrollment criteria were very similar to those of... 

A 70-year-old woman was treated with intravenous alteplase for thrombolysis in acute ischemic stroke and 30 minutes later had acute sinus tachycardia and hypotension, followed by cyanosis and loss of consciousness... 

Immunologic A patient experienced anaphylaxis after an initial bolus and subsequent delayed infusion of alteplase for thrombolysis of acute ischaemic stroke. Although rare, anaphylaxis is a recognized adverse event with alteplase administration, and infusion should be ceased following any symptoms of an anaphylactic reaction to avoid a dose-dependent major reaction [34 ]. 

Protein manipulation for enzyme proteins can serve as a good example of several possible manipulations. Alteplase is a thrombolysis enzyme protein used to prevent death in acute myocardial infarction. The protein has 527 amino acids, 5 disulfide bridges, glycosylation at several amino acids, and 5 peptide domains. Truncation of most domains leaving intact the protease domain resulted in a new biological, reteplase (Retevase), with quite similar thrombolytic activity. Another set of... 

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