1. Livesay, Sarah L.

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Dear Editor:


The letter by Chamberlain and Allison1 highlights an ongoing clinical debate in stroke care, as well as the challenges inherent to writing guidelines and translating those guidelines into clinical practice. The letter questions the use of intravenous thrombolysis with alteplase for the treatment of acute ischemic stroke in the setting of prophylactic administration of low-molecular-weight heparin (LMWH). The American Stroke Association published a scientific rational for the changes to the inclusion and exclusion criteria for alteplase in 2015 recommending against the use of alteplase in patient receiving either a treatment or prophylaxis dose of LMWH.2 A correction was then published that advised against the use of alteplase in patients with ischemic stroke who had received a treatment dose of LMWH within the previous 24 hours, removing patients who received prophylaxis doses from the recommendation.3


It is important to recognize that this topic of thrombolysis in patients with acute ischemic stroke as an inpatient or outpatient who is also receiving LMWH has not been well studied. The initial recommendation and subsequent correction are based on 1 study4 (note the updated reference in the correction) and extrapolating subpopulations from existing trials. The study referenced included only 21 patients who received thrombolysis while on LMWH and an even smaller percentage on only prophylaxis dosing. Overall, patients who received thrombolysis while also receiving a recent dose of LMWH had a higher risk of intracerebral hemorrhage and poor outcome.4 However, the study did not evaluate the role of dosing in the outcome and acknowledged that additional research is needed in this area.


The correction published by Demaerschalk et al3 modified the recommendation to state that "intravenous alteplase in patients who have received treatment doses of LMWH within the previous 24 hours is not recommended (Class III, Level of Evidence B)." In the correction, the authors stop short of making a recommendation on the use of thrombolysis in patients with ischemic stroke on prophylaxis doses of LMWH, likely because of the lack of evidence to develop a recommendation for or against this practice. By removing patients receiving prophylaxis doses within the previous 24 hours from the recommendation, the treating clinician has the flexibility to weigh the risk and benefit of treatment for individual patients.


The process to develop clinical practice guidelines (CPGs) and how to best use them in programs and individual patient care is an important discussion. Clinical practice guidelines, when done well and in accordance with best practice,5 serve as a systematic review of the literature, evaluation of the quality of the literature, and the development of recommendations for clinical practice. They should serve as a resource to start a conversation rather than as rules for practice, particularly in areas where evidence is lacking.


Clinicians may choose to practice differently than recommendations in a CPG, provided they can justify that clinical decision. Patients and their unique clinical situations do not always match the populations or situations studied in clinical trials and included in guidelines. Therefore, it is important to understand that CPGs should guide our practice but should not serve as hard rules for practice. When evidence is of poor quality, inconclusive, or lacking overall, a writing group may either develop a recommendation with a low level of evidence or just not form a recommendation. In the end, a treating clinician must evaluate the existing evidence and any CPG recommendations in the clinical context of an individual patient.


In addition, clinicians and program coordinators should evaluate the quality and development of the guideline and how recommendations were formed. Individual CPG recommendations should always be evaluated for the quality of evidence and how the writing group arrived at the recommendation. Some CPG development methodologies are more transparent than others. Much as we must critically appraise the methodology, results, and implications of clinical research, CPGs should be subject to the same evaluation.


To conclude, although I was not part of the writing group and cannot speak directly to the dialog that influenced the initial recommendation and the subsequent correction, my interpretation of the publications is that thrombolysis with intravenous alteplase in patients with ischemic stroke receiving treatment doses of LMWH is not recommended, and it would be up to a treating practitioner's own clinical judgment to decide to administer thrombolysis in a patient with ischemic stroke on prophylaxis doses of LMWH. These patients may be at a higher risk for hemorrhagic complications, but more research on this topic is needed to form a firmer recommendation or conclusion.




1. Chamberlain J, Allison A. Alteplase administration recommendations for inpatients on low-molecular-weight heparin. J Neurosci Nurs. 2018;50(1):1. [Context Link]


2. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581-641. [Context Link]


3. Correction. Stroke. 2016;47(11):e262. [Context Link]


4. Matute MC, Masjuan J, Egido JA, et al. Safety and outcomes following thrombolytic treatment in stroke patients who had received prior treatment with anticoagulants. Cerebrovasc Dis. 2012;33(3):231-239. [Context Link]


5. IOM. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press; 2011. [Context Link]