In the process of caring for patients suffering from acute ischemic stroke (AIS), a cognitive bias shifts the focus of our typical approach to drug therapy selection. Rather than approach a problem and determine whether a drug is going to help, in the case of alteplase for AIS, we often look for reasons not to give this drug (contraindications) and fail to ask whether the given patient will benefit. Fewer still will ask, what is the patient-oriented benefit? This shift in clinical reasoning is highlighted in this case report describing the reversal of heparin in order to facilitate alteplase administration.(1) This cognitive bias is further reflected in the framing of the issue of whether or not we are treating enough patients with alteplase, as described by the authors quoting epidemiologic data. This bias can be remedied by reflecting on the evidence to support the use of alteplase for AIS. So should we reverse anticoagulation for rt-PA in stroke?
Emergency Medicine Clinical Pharmacist
CHRISTUS Trinity Mother Frances Health System
Emergency Medicine Clinical Pharmacist
Poudre Valley Hospital
- Fontaine, G. V. and Smith, S. M. Alteplase for acute ischemic stroke after heparin reversal with protamine – a case report and review. Pharmacotherapy. Accepted Author Manuscript
- National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke.N Engl J Med. 1995 Dec 14;333(24):1581-7
- Hacke W, Kaste M, Bluhmki E, et al.Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317-29
- Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Höxter G, Mahagne MH, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995 Oct 4;274(13):1017-25.
- Hacke W, Kaste M, Fieschi C, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators.Lancet. 1998 Oct 17;352(9136):1245-51
- Clark WM, Albers GW, Madden KP, Hamilton S. The rtPA (alteplase) 0- to 6-hour acute stroke trial, part A (A0276g) : results of a double-blind, placebo-controlled, multicenter study. Thromblytic therapy in acute ischemic stroke study investigators. Stroke 2000 Apr;31(4):811-6
- 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 Dec 1;282(21):2019-26.
- IST-3 collaborative group. 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.Lancet. 2012 Jun 23;379(9834):2352-63.
- Graham GD. Tissue plasminogen activator for acute ischemic stroke in clinical practice: a meta-analysis of safety data. Stroke. 2003 Dec; 34(12):2847-50.
- Albers GW, Bates VE, Clark WM, et al. Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study. JAMA. March 1 2000;283(9):1145–1150.
- Lopez-Yunez AM, Bruno A, Williams LS, et al. Protocol violations in community-based rTPA stroke treatment are associated with symptomatic intracerebral hemorrhage. Stroke. January 2001;32(1):12–16.
- Tsivgoulis G, Frey JL, Flaster M, et al. Pre-tissue plasminogen activator blood pressure levels and risk of symptomatic intracerebral hemorrhage. Stroke. November 2009;40(11):3631–3634.
- Bravata DM, Kim N, Concato J, Krumholz HM, Brass LM. Thrombolysis for acute stroke in routine clinical practice. Arch Intern Med. 2002;162:1994–2001.
- Jurassic Park, 1993. http://www.imdb.com/title/tt0107290/quotes
- Cucchiara B, Kasner SE, Tanne D, et al. Factors associated with intracerebral hemorrhage after thrombolytic therapy for ischemic stroke: pooled analysis of placebo data from the Stroke-Acute Ischemic NXY Treatment (SAINT) I and SAINT II Trials. Stroke. 2009 Sep;40(9):3067-72.
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